Search Results (27)

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease. It is characterized by mitochondrial dysfunction, increased reactive oxygen species (ROS), α-synuclein (α-syn) and phosphorylated-tau protein (p-tau) aggregation, and dopaminergic neuron cell death. Current drug therapies only provide temporary symptomatic relief and fail to stop or reverse disease progression due to the severe side effects or the blood–brain barrier. This study aimed to investigate the neuroprotective effects of an intermittent heating approach, thermal cycling-hyperthermia (TC-HT), in an in vitro PD model using rotenone (ROT)-induced human neural SH-SY5Y cells. Our results revealed that TC-HT pretreatment conferred neuroprotective effects in the ROT-induced in vitro PD model using human SH-SY5Y neuronal cells, including reducing ROT-induced mitochondrial apoptosis and ROS accumulation in SH-SY5Y cells. In addition, TC-HT also inhibited the expression of α-syn and p-tau through heat-activated pathways associated with sirtuin 1 (SIRT1) and heat-shock protein 70 (Hsp70), involved in protein chaperoning, and resulted in the phosphorylation of Akt and glycogen synthase kinase-3β (GSK-3β), which inhibit p-tau formation. These findings underscore the potential of TC-HT as an effective treatment for PD in vitro, supporting its further investigation in in vivo models with focused ultrasound (FUS) as a feasible heat-delivery approach. Full article

Background: Primary ciliary dyskinesia (PCD) is a rare hereditary disorder caused by defective motile cilia, predominantly affecting the respiratory system. Conductive hearing loss (CHL) due to chronic otitis media with effusion (OME) is a typical feature of PCD, particularly in childhood. However, the underlying mechanisms contributing to sensorineural hearing loss (SNHL) in patients with PCD remain unclear. Methods: We present the case of a 52-year-old male with a clinical diagnosis of PCD, confirmed by the presence of situs inversus, chronic respiratory symptoms, and ultrastructural ciliary defects. Results: Despite a history of recurrent acute otitis media (AOM), the patient developed severe bilateral SNHL, a relatively uncommon and poorly understood manifestation of PCD. Genetic testing revealed a pathogenic SH3TC2 variant, a gene classically associated with Charcot–Marie–Tooth disease type 4C (CMT4C), raising the possibility of an alternative or contributory genetic etiology for the patient’s auditory dysfunction. Conclusions: This case highlights the importance of comprehensive audiological and genetic evaluations in PCD patients, particularly those presenting with progressive or atypical HL. The presence of a pathogenic SH3TC2 mutation suggests a potential neuropathic component to the patient’s HL, underscoring the need for further research into the intersection between ciliary dysfunction and genetic neuropathies. Early identification and intervention are critical to optimizing auditory outcomes and quality of life in affected individuals. Full article

The microphysical characteristics of precipitation and their differences among four typical weather systems over Hainan Island were investigated via multi-source observations from 2019 to 2023. We find that the cold fronts (CFs) have the greatest concentration of small raindrops, with a more substantial raindrop condensation process. The subtropical highs (SHs), with primarily deep convection and more prominent evaporation at low levels, lead to greater medium-to-large raindrops (diameters > 1 mm). Tropical cyclones (TCs) are characterized mainly by raindrop condensation and breakup, resulting in high concentrations of small raindrops and low concentrations of large raindrops. The trough of low pressures (TLPs) produces the lowest concentration of small raindrops because of evaporation processes. The convective clusters of the SHs are between maritime-like and continental-like convective clusters, and those of the other three types of weather systems are closer to maritime-like convective clusters. The relationships between the shape parameter (μ) and the slope parameter (Λ), as well as between the reflectivity factors (Z) and the rain rates (R), were established for the four weather systems. These results could improve the accuracy of radar quantitative precipitation estimation and the microphysical parameterizations of numerical models for Hainan Island. Full article

Human induced pluripotent stem cells (hiPSCs) represent a powerful tool to investigate neuropathological disorders in which the cells of interest are inaccessible, such as in the Charcot–Marie–Tooth disease (CMT), the most common inherited peripheral neuropathy. Developing appropriate cellular models becomes crucial in order to both study the disease’s pathophysiology and test new therapeutic approaches. The generation of hiPS cellular models for disorders caused by a single nucleotide variation has been significantly improved following the development of CRISPR-based editing tools. In this study, we efficiently and quickly generated, by CRISPR editing, the two first hiPSCs cellular models carrying alterations involved in CMT4C, also called AR-CMTde-SH3TC2. This subtype of CMT is associated with alterations in the SH3TC2 gene and represents the most prevalent form of autosomal recessive demyelinating CMT. We aimed to develop models for two different SH3TC2 nonsense variants, c.211C>T, p.Gln71* and the most common AR-CMTde-SH3TC2 alteration, c.2860C>T, p.Arg954*. First, in order to determine the best CRISPR strategy to adopt on hiPSCs, we first tested a variety of sgRNAs combined with a selection of recent base editors using the conveniently cultivable and transfectable HEK-293T cell line. The chosen CRISPR base-editing strategy was then applied to hiPSCs derived from healthy individuals to generate isogenic CMT disease models with up to 93% editing efficiency. For point mutation generation, we first recommend to test your strategies on alternative cell line such as HEK-293T before hiPSCs to evaluate a variety of sgRNA-BE combinations, thus boosting the chance of achieving edited cellular clones with the hard-to-culture and to transfect hiPSCs. Full article

Shear-keyed inter-modular connections (IMCs) are integral components of high-rise modular steel structures (MSSs), providing robust interconnectivity to support grouped tubular columns across modules, thereby introducing column discontinuities and distinctive structural behavior. This study conducted a comprehensive numerical assessment and theoretical analysis of the axial compression behavior of grouped tubular columns based on a validated finite element model (FEM), which captured the member-to-structural level behavior of steel hollow section (SHS) columns and accommodated geometric imperfections. An FEM was initially developed and validated using 28 axial compression tests documented in the literature, comprising 15 tests on cold-formed and 13 on hot-rolled steel hollow section (SHS) columns. The primary parameters explored in tests included material properties (stainless/carbon), processing methods (cold-formed/hot-rolled), cross-section sizes (D/B), cross-sectional or member slenderness ratios (D/t_c, B/t_c, or L_c/r), and the number of columns (1, 7, and 11). A comprehensive parametric numerical study involving 103 grouped tubular column FEMs then investigated the influence of initial imperfection, shear-key height (L_t), thickness (t_t), steel tube length (D), width (B), thickness (t_c), and height (L_c) alongside the effects of space between tube and key, and the gap between tubes. The results indicated that the load-shortening behavior of the grouped columns consists of linear elastic, inelastic, and recession stages. The failure modes observed primarily displayed an S-shaped pair of inward and outward local buckling on the outer sides and double S-shaped local buckling on the interior sides. The buckling arose near the shear key or at 1/4 or 1/2 of the column height. None of the considered models experienced global buckling. Increasing t_t, L_t, t_c, D, or B enhances strength and stiffness, while L_c or L_c/r linearly affects stiffness and ductility. The columns’ nominal axial strength was reduced because of the shear keys, which decreased compression yielding and caused localized elastic buckling. Subsequently, the theoretical analysis revealed that the design codes do not capture this behavior, and thus, their capacity estimate yields inaccurate findings. This discrepancy renders existing code prediction equations, including those from Indian (IS800), New Zealand (NZS400), European (EC3:1-1), Canadian (CSA S16), American (AISC360-16), and Chinese (GB50017) standards, as well as the model proposed by Li et al., non-conservative. To assure conservative results, the paper recommended modification of existing standards and proposed prediction equations based on a fourth-order differential equation that describes the actual behavior of modular steel columns grouped with shear keys. The proposed design approach accurately predicted the axial compression capacity of modular steel-grouped columns, proving conservative yet effective. This provides valuable data that could transform design and construction techniques for MSSs, extending to various column and IMC forms through adaptable design parameters. This enhancement in structural performance and safety significantly contributes to the advancement of modular construction practices. Full article

This review investigates the intricate relationship between hyperparathyroidism (HPT) and thyroid carcinoma (TC), aiming to elucidate their coexistence, potential pathogenetic mechanisms, and clinical implications. A systematic search strategy, employing the MeSH terms ‘Hyperparathyroidism’ and ‘Thyroid Carcinoma’, spanned publications from 2013 to 2023 across the PubMed, Web of Science, and Scopus databases. Fifteen selected articles were analyzed. Studies unanimously confirm the notable association between primary hyperparathyroidism (PHPT) and thyroid nodules/cancer, with incidences ranging from 2.8% to 47.1%. Key findings reveal a predilection for papillary thyroid carcinoma (PTC) in this association, showcasing varying tumor characteristics and gender disparities. Lower preoperative serum parathyroid hormone (PTH) levels are a potential risk factor for thyroid cancer in PHPT patients. Diverse surgical approaches and tumor characteristics between PHPT and secondary hyperparathyroidism (SHPT) cases were noted. Moreover, this review underscores the scarcity of definitive guidelines in managing concurrent PHPT and thyroid conditions, advocating for comprehensive assessments to enhance diagnostic accuracy and refine therapeutic interventions. Rare coincidental associations, as highlighted by case reports, shed light on unique clinical scenarios. In essence, this review amalgamates evidence to deepen the understanding of the interplay between HPT and TC, emphasizing the need for further research to elucidate underlying mechanisms and guide clinical management. Full article

Oxidative stress is closely associated with the pathology of neurodegenerative diseases. The seeds of Carthamus tinctorius L. (CTS) and Taraxacum coreanum (TC) are reported as herbal medicines for neuroprotection. This study investigated the protective effect of CTS, TC, and their combination against oxidative stress induced by H₂O₂ in SH-SY5Y cells. The CTS and TC combination dose-dependently increased DPPH and ·OH radical scavenging activities compared with non-combination. The combination showed a higher increased cell survival rate in H₂O₂-stimulated SH-SY5Y cells than CTS or TC. Moreover, CTS, TC, and their combination-treated cells reduced LDH release and apoptotic cells. CTS, TC, and their combination also inhibited NO and ROS generation. Further, the combination of up-regulated antioxidant enzymes (superoxide dismutase and glutathione peroxidase) and Bcl-2 protein expressions and down-regulated Bax expression. These findings suggest that the combination of CTS and TC may be beneficial to prevent and treat oxidative stress-mediated neurodegenerative diseases. Full article

The devastating impact of a circumflex coronary artery (CX) injury during mitral valve (MV) surgery is well reported. Despite significant improvements in preoperative risk assessment, intraoperative diagnosis and perioperative treatment strategies of CX injury during MV surgery, recent reports re-emphasize the variability in presentation, the unpredictable mechanisms of injury and the conflicting evidence regarding perioperative management. The progressive transition from conventional sternotomy access to minimally invasive surgical and transcatheter (TC) interventions for MV disease are associated with significant learning curves and require additional single-shaft and robotic console suture manipulation skills with special attentiveness to the potential risk of CX injury. The introduction of hybrid theatres that facilitate single stage surgical and TC interventions also provides new intraoperative diagnostic and therapeutic options without transporting unstable patients for percutaneous coronary intervention (PCI) assessment. By utilizing a MeSH terms-based PubMed search, a total of 89 patients with CX injury that occurred during MV surgery was identified from 49 reports between 1967 and 2022. MV surgery was performed by conventional sternotomy (n = 76, 85.4%), endoscopic (n = 12, 13.4%) and robotic access (n = 1, 1.1%), with 35 injuries (39.3%) resulting in total CX occlusion. Rescue PCI was utilized in 40 patients (44.9%). This manuscript provides a systematic overview of all available historic and contemporary reports on CX injury during MV surgery, outlines recent refinements in CX injury mechanisms, describes current MV surgery associated CX injury prevention and diagnosis and treatment strategies and highlights important MV procedural aspects that may minimize the risk and consequences of CX injury. Full article

Introduction: Tissue conditioners have been widely used in various clinical applications in dentistry, such as treating inflamed alveolar ridges, temporarily relining partial and complete dentures, and the acquisition of functional impressions for denture fabrication. This study aimed to investigate the mechanical properties of the most prevalent tissue conditioner materials on the market, including Tissue Conditioners (TC), Visco Gel (VG), and FITT (F). Materials and Methods: The three tissue conditioners, TC, VG, and F, were assessed based on the parameters mentioned above. The following tests were performed based on the ISO 10139-1 and ISO 10139-2 requirements: Shore A hardness, denture plate adhesion, sorption, water solubility, and contraction after 1 and 3 days in water. Additional tests are described in the literature, such as ethanol content and gelling time. The tests were carried out by storing the materials in water at 37 °C for 7 days. Results: The gel times of all tested materials exceeded 5 min (TC = 300 [s], VG = 350 [s]). In vitro, phthalate-free materials exhibited higher dissolution in water after 14 days (VG = −260.78 ± 11.31 µg/mm²) compared to F (−76.12 ± 7.11 µg/mm²) and experienced faster hardening when stored in distilled water (F = 33.4 ± 0.30 Sh. A, VG = 59.2 ± 0.60 Sh. A). They also showed greater contractions. The connection of all materials to the prosthesis plate was consistent at 0.11 MPa. The highest counterbalance after 3 days was observed in TC = 3.53 ± 1.12%. Conclusions: Materials containing plasticizers that are not phthalates have worse mechanical properties than products containing these substances. Since phthalates are not allowed to be used indefinitely in medical devices, additional research is necessary, especially in vivo, to develop safe materials with superior functional properties to newer-generation alternatives. In vitro results often do not agree fully with those of in vivo outcomes. Full article

The implementation of NGS methods into clinical practice allowed researchers effectively to establish the molecular cause of a disorder in cases of a genetically heterogeneous pathology. In cases of several potentially causative variants, we need additional analysis that can help in choosing a proper causative variant. In the current study, we described a family case of hereditary motor and sensory neuropathy (HMSN) type 1 (Charcot–Marie–Tooth disease). DNA analysis revealed two variants in the SH3TC2 gene (c.279G>A and c.1177+5G>A), as well as a previously described variant c.449−9C>T in the MPZ gene, in a heterozygous state. This family segregation study was incomplete because of the proband’s father's unavailability. To evaluate the variants’ pathogenicity, minigene splicing assay was carried out. This study showed no effect of the MPZ variant on splicing, but the c.1177+5G>A variant in the SH3TC2 gene leads to the retention of 122 nucleotides from intron 10 in the RNA sequence, causing a frameshift and an occurrence of a premature stop codon (NP_078853.2:p.Ala393GlyfsTer2). Full article

This study focused on Middle Permian Lucaogou Formation saline lake source rocks, utilizing a combination of biomarkers and hydrocarbon generation thermal simulation to analyze their biological compositions, depositional environments, and hydrocarbon generation potential. The Pr/Ph ratio, Ph/nC₁₈ ratio, and Pr/nC₁₇ ratio indicate that the Lucaogou Formation was in a reducing environment during the deposition period, and the lower part of the Lucaogou Formation (P₂l₁) is more anoxic than the upper part of the Lucaogou Formation (P₂l₂). The maturity index 20S (%) and ββ (%) reflect that the maturity of organic matter in the P₂l₁ is slightly higher than that in the P₂l₂. The G/H index and the ETR index indicate that the stratification of the water column is better during the sedimentary period of Lucaogou Formation and the salinity of the P₂l₁ is higher than that of the P₂l₂. The biomarker parameters of nC₂₁₋/nC₂₂₊, CPI, S/H, and C₂₂T/C₂₁T reflect that the organic matter of the source rocks have a higher abundance of bacteria and algae than higher plants, and the contents of bacteria are more than that of algae. The (7- + 8-MMAs)/C_max and (C₂₈ + C₂₉ − St)/St parameters indicate that cyanobacteria accounted for a certain proportion of bacteria, and the algae are mainly green algae. The co-evolution of the sedimentary environment and the biological composition reflects the control of the sedimentary paleoenvironment on biological composition. According to the relative content of cyanobacteria, green algae, and Rhodophyta, the source rocks of the upper and lower Lucaogou Formation correspond to the low-salinity type (LS-type) and the high-salinity type (HS-type), respectively. Compared with LS-type source rocks, HS-type source rocks have greater generation potential of oil and weaker gas generation potential. This study is valuable for the accurate assessment of source rocks and holds significant practical implications for the exploration of oil and gas resources. Full article

In this study, the author examined the tropical cyclone (TC) activity over the southern hemisphere (SH) and its relationship with tropical climate modes, such as the El Niño–Southern Oscillation (ENSO), during the austral summer (December–January–February; DJF) and fall (March–April–May; MAM). The correlation analysis between the TC activity and the global sea surface temperature (SST) suggested that an increased TC activity over the southwestern and southeastern Indian Ocean (SWIO and SEIO) was associated with a La Niña-like SST pattern, while an increased TC activity over the southwestern Pacific (SWP) was associated with an El Niño-like SST pattern. The atmospheric conditions accompanying the TC increase over the SWIO/SEIO indicated that a La Niña induces tropospheric cooling over the tropics with cyclonic circulation anomalies over the TC genesis region. Both the SST anomalies and the cyclonic circulation anomalies were significantly correlated with TC genesis parameters, suggesting that they contributed to TC genesis. To investigate the SST precursors, a lead-lag correlation analysis was performed. For the TC variations over the SEIO, an SST pattern that resembled the Pacific Meridional Mode (PMM) was statistically significant at a two-season lead. However, such a TC-ENSO relationship is seasonally dependent, with different patterns during DJF and MAM. These results suggest that the Matsuno-Gill response to ENSO is an important factor in TC activity but that this influence is seasonally modulated over the SH. Full article

The technology for storing thermal energy as sensible heat, latent heat, or thermochemical energy has greatly evolved in recent years, and it is expected to grow up to about 10.1 billion US dollars by 2027. A thermal energy storage (TES) system can significantly improve industrial energy efficiency and eliminate the need for additional energy supply in commercial and residential applications. This study is a first-of-its-kind specific review of the current projected performance and costs of thermal energy storage. This paper presents an overview of the main typologies of sensible heat (SH-TES), latent heat (LH-TES), and thermochemical energy (TCS) as well as their application in European countries. With regard to future challenges, the installation of TES systems in buildings is being implemented at a rate of 5%; cogeneration application with TES is attested to 10.2%; TES installation in the industry sector accounts for 5% of the final energy consumption. From the market perspective, the share of TES is expected to be dominated by SH-TES technologies due to their residential and industrial applications. With regard to the cost, the SH-TES system is typically more affordable than the LH-TES system or the TCS system because it consists of a simple tank containing the medium and the charging/discharging equipment. Full article

Interdecadal change in the relationship between the winter Siberian high (SH) and tropical cyclone genesis frequency (TCGF) is investigated using observational and reanalysis data. Focus is on the Western North Pacific (WNP) where environmental background associated with TCGF is closely related to the winter SH. It is demonstrated that the relationship presents clear interdecadal change during 1980–2020. A significant negative correlation dominates in the last two decades of the 20th century (P1), but it clearly weakens from the early 2000s onward (P2). Observational evidence shows that such interdecadal change is related dominantly to variations in the air–sea responses associated with the winter SH over the North Pacific. During P1, when the SH is anomalously strengthened, an Aleutian Low (AL) response occurs over the downstream North Pacific, which gradually develops into a meridional dipole distribution pattern consistent with the negative North Pacific Oscillation (NPO) mode during the following spring. The northeasterly wind anomaly over the subtropical North Pacific maintains and further delivers into the tropical Pacific. It favors easterly wind anomaly enhancement over the tropical Pacific around summer and grows into an anticyclonic circulation response in the WNP, which restrains the genesis of TCs. During P2, the eastward shift of the SH anomaly favors a weak AL over the Northeast Pacific followed by a northeastward-shifted anticyclone over the subtropical central-eastern Pacific, which confines the relatively weak northeasterly wind anomalies far away from the tropical Pacific. This was concurrent with a weakening relationship between the SH and WNP TCGF, indicating weaker downstream impacts of the winter SH. Full article

Dyslipidemia has been linked to breast cancer incidence. The aim of the present meta-analysis was to further investigate the relationship between the serum lipid profile and breast cancer risk. Databases such as PubMed, EMBASE, and Web of Sciences were searched up to the end of January 2021 using certain MeSH and non-MeSH keywords and combinations to extract related published articles. Twenty-six prospective studies involving 1,628,871 women, of whom 36,590 were diagnosed with breast cancer during the follow-up period met the inclusion criteria. A negative and significant association was found between the HDL-C level and the risk of breast cancer (relative risk (RR): 0.85, 95% CI: 0.72–0.99, I²: 67.6%, p = 0.04). In contrast, TG (RR: 1.02, 95% CI: 0.91–1.13, I²: 54.2%, p = 0.79), total cholesterol (TC) (RR: 0.98, 95% CI: 0.90–1.06, I²: 67.2%, p = 0.57), apolipoprotein A (ApoA) (RR: 0.96, 95% CI: 0.70–1.30, I²: 83.5%, p = 0.78) and LDL-C (RR: 0.93, 95% CI: 0.79–1.09, I²: 0%, p = 0.386) were not associated with breast cancer development. In studies adjusting for hormone use and physical activity, breast cancer risk was positively correlated with TC (RR: 1.05, 95% CI: 1.01–1.10). Similarly, TG was significantly related to breast cancer development after adjustment for baseline lipids (RR: 0.92, 95% CI: 0.85–0.99) and race (any races mentioned in each study) (RR: 1.80, 95% CI: 1.22–2.65). In the present meta-analysis, HDL-C was inversely related to breast cancer risk. Overall, data on the links between lipids and breast cancer are conflicting. However, there is increasing evidence that low HDL-C is related to an increased risk for this type of malignancy. Full article