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Obesity increases the risk for a number of diseases including cardiovascular diseases and type 2 diabetes. Excess saturated fatty acids (SFAs) in obesity play a significant role in cardiovascular diseases by activating innate immunity responses. However, the mechanisms by which SFAs activate the innate immune system are not fully known. Here we report that palmitic acid (PA), the most abundant circulating SFA, induces myocardial inflammatory injury through the Toll-like receptor 4 (TLR4) accessory protein MD2 in mouse and cell culture experimental models. Md2 knockout mice are protected against PA- and high-fat diet-induced myocardial injury. Studies of cell surface binding, cell-free protein–protein interactions and molecular docking simulations indicate that PA directly binds to MD2, supporting a mechanism by which PA activates TLR4 and downstream inflammatory responses. We conclude that PA is a crucial contributor to obesity-associated myocardial injury, which is likely regulated via its direct binding to MD2. The free fatty acid-mediated inflammatory activities are regulated through TLR4. Here the authors show that palmitic acid binds to MD2, initiating complex formation with TLR4, recruitment of MyD88, and subsequent activation of pro-inflammatory molecules, and that MD2 blockade protects against diet-induced cardiac dysfunction.

Alcoholic liver disease (ALD) remains a major global health burden, and effective therapeutic options are limited. Quercetin, a dietary flavonoid with antioxidant and anti-inflammatory properties, has shown hepatoprotective potential, but its mechanisms in acute alcohol-induced liver injury require clarification. Fifty male BALB/c mice were randomly divided into five groups (n = 10/group): control (CG), model (MG), low-dose quercetin (LQ, 50 mg/kg), high-dose quercetin (HQ, 100 mg/kg), and oyster soybean carnitine mice in the oyster soybean carnitine group (OG) were administered oyster soybean carnitine at a volume of 20 mL/kg.(OG, 20 mL/kg). All treatments were administered orally once daily for 14 days. Acute alcohol injury was induced on Day 14 using 52% (v/v) ethanol. Behavioral intoxication indices, serum biochemistry, liver oxidative stress markers, inflammatory cytokines, histopathology, lipid accumulation, and the expression of lipid-metabolismrelated genes and proteins (FAS, SCD1, ACC1, CPT1, PGC-1α, PPARα) were assessed. HQ significantly prolonged alcohol tolerance time (P < 0.01) and shortened sober-up time (P < 0.01). HQ markedly reduced serum AST, ALT, TG, FFA, and glycerol levels (P < 0.01). Quercetin also lowered hepatic TG, TNF-α, and IL-6 and increased SOD, GSH, and CAT activities. Histological and Oil Red O staining confirmed reduced steatosis. Mechanistically, quercetin downregulated hepatic FAS, SCD1, and ACC1 while upregulating CPT1, PGC-1α, and PPARα at both mRNA and protein levels. Quercetin exerts hepatoprotective effects against acute alcohol-induced liver injury through coordinated regulation of lipid metabolism, oxidative stress, and inflammatory responses.The study did not include a quercetin-only group or measure blood ethanol levels, which should be addressed in future work.These findings support the potential of quercetin as a natural candidate for preventing alcohol-related hepatic injury.

Clinical data Chlamydia psittaci pneumonia is a community-acquired pneumonia caused by Chlamydia psittaci. While severe cases may lead to critical conditions such as respiratory failure, splenic infarction is relatively uncommon. A severe patient with Chlamydia psittaci pneumonia admitted to our hospital experienced a splenic infarction during treatment. Fortunately, the patient’s situation was improved after careful treatment. Now, the patient has been discharged. Further exploration of the mechanism of concurrent splenic infarction is required. Backgroud Psittacosis pneumonia, a zoonotic infectious disease transmitted from birds to humans, is caused by Chlamydia psittaci and represents a type of chlamydial pneumonia [ 1 ]. Insome instances, the disease may progress to severe pneumonia and respiratory failure, necessitating intensive support measures, including mechanical ventilation. The advent of technologies such as Metagenomic Next-Generation Sequencing (mNGS) for the etiological diagnosis of infectious diseases [ 2 ] has improved the diagnostic and treatment success rates for Psittacosis. Instances of severe chlamydial pneumonia with complications such as splenic infarction are uncommon. A patient with severe Psittacosis pneumonia complicated by splenic infarction was admitted to the Emergency Intensive Care Unit (EICU) of Haining People’s Hospital and subsequently improved following effective anti-infective and anticoagulant therapy. This report is provided herein.

Backgrounds/aims Nerve guide conduits (NGCs) offer promise for peripheral nerve regeneration, yet their performance remains inferior to autologous nerve grafts. To address this limitation, we developed novel aligned silk fibroin nerve conduits (ASNC) and evaluated their performance in enhancing nerve regeneration. Materials and methods ASNCs were fabricated and their biocompatibility and regenerative potential were assessed in vitro and in vivo. Random silk fibroin nerve conduits (RSNCs) served as control materials. In vitro experiments evaluated ASNC effects on cell adhesion, proliferation, and morphological elongation. For in vivo studies, a 10-mm-long sciatic nerve defect rat model was established, followed by ASNCs treatment. Post-implantation evaluations included axonal regeneration (sciatic function index, myelinated fiber density, muscle weight preservation) and functional recovery (walking track analysis, electrophysiology, histological evaluations). Results Compared to RSNCs, ASNCs significantly promoted cell adhesion and directional growth along the aligned fibers, whereas RSNCs exhibited slower growth and random orientation. In vivo results showed ASNCs achieved axonal regeneration and functional recovery comparable to autografts. This was demonstrated by improvements in the number and area of myelinated nerve fibers and enhanced muscle wet weight ratios. Conclusions The newly developed ASNCs demonstrated comparable effectiveness to autografts in guiding axonal growth and promoting nerve regeneration. These findings position ASNCs as a promising alternative to autologous nerve grafts, offering a viable therapeutic approach for peripheral nerve repair. Impact statement This study demonstrates that aligned silk fibroin nerve conduits (ASNCs) significantly enhance peripheral nerve regeneration, achieving functional recovery comparable to autologous nerve grafts. By leveraging the directional guidance of aligned fibers, ASNCs promote axonal growth and mitigate the limitations of current treatments, such as donor site morbidity and insufficient donor tissue availability. These findings advance the field of neural tissue engineering by providing a scalable, biomaterial-based alternative for peripheral nerve repair. The potential clinical translation of ASNCs offers a promising therapeutic strategy for addressing long-gap nerve defects, with implications for improving patient outcomes and expanding treatment options.

Introduction:The aim of the study was to examine the association between frailty and osteoarthritis.Material and methods:We conducted a cross-sectional study in the National Health and Nutrition Examination Survey, while logistic regression was used to explore the association of the two. Mendelian randomization (MR) study was used to explore the causal relationship between the two.Results:In the cross-sectional study, logistic regression analysis showed that odds ratio (OR) (95% CI) value was 1.07 (1.05, 1.08). In the MR study, the inverse-variance weighting (IVW) results showed OR (95% CI) value of 1.69 (1.01–2.83).Conclusions:There is both a correlation and a causal relationship between frailty and osteoarthritis, and frailty may be a potentially better response than age to osteoarthritis.

Conserved across all kingdoms of life, ABC transporters comprise one of the largest protein families. They are associated with multidrug resistance, affecting aspects such as resistance to antimicrobials or anti-cancer drugs. ATP-binding cassette (ABC) transporters represent one of the largest protein superfamilies. Functionally diverse, ABC transporters have been implicated in many aspects of microbial physiology. The genome of the human fungal pathogen Cryptococcus neoformans encodes 54 putative ABC transporters and most of them remain uncharacterized. In a previous genetic screen for fungal regulators of phagocytosis, we identified an uncharacterized gene, CNAG_06909, that modulates host interactions. This gene encoded a half-size ABC transporter of the PDR-type, and phenotypic studies of a strain with this gene deleted revealed an altered antifungal susceptibility profile, including hypersensitivity to fluconazole (FLC). This gene, which we named PDR6 , localized to the endoplasmic reticulum (ER) and plasma membrane (PM), and when absent, less ergosterol was observed in the PM. Additionally, we observed that the pdr6 Δ strain displayed a reduction in secreted polysaccharide capsular material. These changes to the cellular surface may explain the observed increased uptake by macrophages and the reduced intracellular survival. Finally, studies in mice demonstrated that Pdr6 function was required for the normal progression of cryptococcal infection. Taken together, this study demonstrates a novel dual role for PDR transporters in C. neoformans , which could represent a potential target for antifungal therapeutics. Furthermore, the atypical half-size transporter encoded by PDR6 is conserved in many fungal pathogens, but absent in model nonpathogenic fungi. Hence, this study provided a function for this unique group of fungal half-size PDR transporters that, although conserved, remain largely understudied. IMPORTANCE Conserved across all kingdoms of life, ABC transporters comprise one of the largest protein families. They are associated with multidrug resistance, affecting aspects such as resistance to antimicrobials or anti-cancer drugs. Despite their importance, they are understudied in fungal pathogens. In the environmental fungus Cryptococcus neoformans , a leading cause of fungal infections, only a few ABC transporters have been studied. Here, we characterized an atypical, half-size, ABC transporter of the PDR-type, that affected both antifungal resistance and host-pathogen interactions. PDR-type transporters are only present in fungi and plants, and this subgroup of half-size transporters was conserved in fungal pathogens, yet their function was completely unknown. Because the current treatments for cryptococcal infection are suboptimal, understanding the mechanisms of antifungal resistance and the host interactions that drive the infection is critical to improving the management of this disease. Here, we provide insights into these important aspects of cryptococcal pathogenesis.

The temperature-dependent polarization performance of super-twisted nematic liquid crystals (STN-LCs) when used as polarizers has garnered considerable scholarly attention. In this study, the transmittance of an STN-LC cell was measured under incident light wavelengths of 650 nm, 532 nm, and 405 nm over the temperature range of 30 °C to 100 °C. The STN-LC cell was employed both as the sample under test and as an analyzer in a rotational measurement setup to investigate how its polarization properties vary with temperature. The results indicate that the LC cell exhibits the characteristics of a linear polarizer under red light (650 nm) and violet laser (405 nm) across the full temperature range. However, under green laser (532 nm), when the temperature exceeds 60 °C, its extinction ratio is poor, suggesting its unsuitability for polarization applications under such conditions. A birefringence inversion formula was derived using the transmittance difference method, which effectively eliminates the influence of the glass substrates on the measured transmittance of the LC layer. Utilizing this method, a simple optical setup consisting of a polarizer and photodetector was constructed to accurately extract the birefringence of the LC. The birefringence of super-twisted nematic liquid crystal can be obtained by the transmittance difference method, which is low-cost, has a simple optical path, and is convenient for temperature-controlled experimental measurements of the liquid crystal cell. The findings of this study provide methodological support for the precise determination of birefringence in LCs exhibiting linear polarization characteristics.

The acceleration of digital technology development is an important strategic choice to realize the transformation of green innovation. Prior research focuses on the mechanism by which artificial intelligence technology promotes economic growth but ignores the impact of digital technology on green innovation performance. Using panel data on 30 regions in China from 2003 to 2019, this paper examines the impact of digital technology on green innovation performance. The results are as follows: (1) Digital technology can significantly promote green innovation performance. After a series of robustness tests, the conclusion is still valid. (2) Digital technology improves green innovation performance through the green technology upgrading effect, cost reduction effect, and green resource allocation optimization effect. (3) Heterogeneity test results show that in regions with high human capital, high R&D intensity, and strong environmental regulation, the improvement effect of digital technology on green innovation performance is more obvious. These findings not only enrich the literature on digital technology and green innovation performance but also serve as a reference for governmental departments as they optimize their strategy for developing digital technology and achieving green economic development.

Cryptococcal pneumonia is a severe fungal infection of the respiratory system, predominantly caused by Cryptococcus neoformans . Its incidence is increasing, driven by evolving pathogen dynamics and heightened susceptibility among patient populations. This investigation aimed to assess the combined therapeutic efficacy of Fluconazole and Amphotericin B for cryptococcal pneumonia and to explore the roles of miR-15b and TGF-β1 in modulating treatment response. Twenty-eight patients diagnosed with cryptococcal pneumonia were randomly allocated to receive either Amphotericin B monotherapy (control group) or a combination of Amphotericin B and Fluconazole (observation group) over a 14-day period. Key respiratory function indices—forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratios—were measured pre- and post-treatment, alongside levels of procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), miR-15b, and TGF-β1. Results demonstrated marked improvements in pulmonary function within the observation group, with significantly higher FEV1, FVC, and FEV1/FVC values than those in the control group ( P  < 0.05). Additionally, the observation group exhibited greater reductions in PCT and sTREM-1, coupled with notable elevations in miR-15b and TGF-β1 levels. The combination therapy achieved a total response rate of 92.86%, significantly surpassing the control’s 57.14% efficacy ( P  < 0.05). These findings indicate that Fluconazole combined with Amphotericin B not only enhances clinical efficacy by mitigating inflammation but also supports lung function recovery with a favourable safety profile, highlighting its utility in managing cryptococcal pneumonia effectively.

Global measurements of total ozone are necessary to evaluate ozone hole recovery above Antarctica. The Environmental Trace Gases Monitoring Instrument (EMI) onboard GaoFen 5, launched in May 2018, was developed to measure and monitor the global total ozone column (TOC) and distributions of other trace gases. In this study, some of the first global TOC results of the EMI using the differential optical absorption spectroscopy (DOAS) method and validation with ground-based TOC measurements and data derived from Ozone Monitoring Instrument (OMI) and TROPOspheric Monitoring Instrument (TROPOMI) observations are presented. Results show that monthly average EMI TOC data had a similar spatial distribution and a high correlation coefficient (R ≥ 0.99) with both OMI and TROPOMI TOC. Comparisons with ground-based measurements from the World Ozone and Ultraviolet Radiation Data Centre also revealed strong correlations (R > 0.9). Continuous zenith sky measurements from zenith scattered light differential optical absorption spectroscopy instruments in Antarctica were also used for validation (R = 0.9). The EMI-derived observations were able to account for the rapid change in TOC associated with the sudden stratospheric warming event in October 2019; monthly average TOC in October 2019 was 45% higher compared to October 2018. These results indicate that EMI TOC derived using the DOAS method is reliable and has the potential to be used for global TOC monitoring.