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Skin cancers continue to present unresolved challenges, particularly regarding the association with sex hormones, which remains a topic of controversy. A systematic review is currently warranted to address these issues. To analyze if sex hormones result in a higher incidence of skin cancers (cutaneous melanoma, basal cell carcinoma, squamous cell carcinoma). Data sources and study selection—The database of PubMed, Embase and Web of Science (WOS) was searched until July 3, 2024. The search yielded 1016 articles. 42 eligible studies were identified for meta-analysis. Data extraction and synthesis—Eligible trials reported skin cancer data and outcomes, confirming diagnoses and collecting hormone use information. Other extracted data included study methods, demographics, and reproductive factor. Relative risk (RR) and odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI), were synthesized after adjusting. The primary outcome was the incidence of cutaneous melanoma and non-cutaneous melanoma. 95% CI and OR are estimate effects. Participants using oral contraceptives (OCs) showed a higher incidence of cutaneous melanoma (CM) [OR 1.08, 95%CI 1.03–1.13, p < 0.01]. There is positively related statistic difference in Squamous cell carcinoma (SCC) [OR 1.37, 95%CI 1.15–1.63, p < 0.01]. Hormone replacement therapy (HRT) was associated with a higher incidence of CM [OR 1.18, 95%CI 1.13–1.24, p < 0.01]. And for non-melanoma skin cancer (NMSC), HRT also increased the incidence [OR 1.13, 95%CI 1.03–1.24, p = 0.01]. Menopausal hormone therapy (MHT) also showed an increased incidence of CM [OR 1.09, 95%CI 1.00–1.18, p < 0.05]. For age at first birth, > 30 years demonstrated a positive correlation with increased the incidence of CM [OR 1.21, 95%CI 1.00–1.46, p = 0.05]. OCs and HRT were associated with increased risks of skin cancers. MHT elevated the risk of CM. In women whose menopause age was older than 50 years, endogenous sex hormones decreased gradually, which caused higher risks of skin cancers. First birth aged older than 30 years indicated increasing effects of skin cancers. Trial registration number : CRD42024517445 [ABSTRACT FROM AUTHOR]

Accurately estimating particulate organic nitrate under high NOx and oxidizing conditions is critical. This study compared the NOx+ ratio, unconstrained Positive Matrix Factorization (PMF), and Multilinear Engine-2 (ME2) methods to estimate particulate organic nitrate in Shanghai across different seasons. The factors associated with organic nitrate, as identified through two receptor methods, exhibited consistent daily patterns in spring, summer, and autumn, although source contributions varied. The NOx+ ratio method reported higher organic nitrate levels than the PMF and ME2 methods, likely due to the fixed RON/RAN parameter. Seasonal RON/RAN parameters were optimized based on precursor emissions in Shanghai, achieving values of 3.13 in spring, 2.25 in summer, and 1.88 in autumn. This optimization reduced discrepancies in organic nitrate using the NOx+ ratio to 3.2–7.4%. The optimized parameters in this study support the rapid and accurate estimation of organic nitrate during different seasons in urban areas. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) have been recognized as essential regulators in various human malignancies. Hundreds of lncRNAs were known to be abnormally expressed in renal cell carcinoma (RCC) through a lncRNA expression microarray, among which lncRNA OSTM1 antisense RNA 1(OSTM1-AS1) was revealed as one of the most abundant lncRNAs. However, the function of OSTM1-AS1 in RCC remains unknown. Here, we examined OSTM1-AS1 functional roles and mechanism in RCC development. OSTM1-AS1 expression was significantly highly expressed among RCC tissue specimens and cell lines. Functionally, OSTM1-AS1 knockdown significantly suppressed cell proliferation, migration along with metastasis of RCC cells. Mechanistically, miR-491-5p was targeted via OSTM1-AS1, and down-regulation of miR-491-5p reversed OSTM1-AS1 knockdown impact on RCC migration and invasion. MMP-9 was targeted via miR-491-5p, and MMP-9 overexpression reversed miR-491-5p or OSTM1-AS1 knockdown impact on cell migration and invasion. MMP-9 abundance was decreased by OSTM1-AS1 silence, that was reduced by miR-491-5p deficiency. Importantly, our investigation revealed that OSTM1-AS1 has the ability to interact with miR-491-5p, thereby increasing the MMP-9 expression. The in vivo trial demonstrated that OSTM1-AS1 suppression resulted in tumor growth inhibition among nude mice. In summary, our findings indicate, for the first time, at least to the best of our knowledge, that OSTM1-AS1 serves as an oncogene among RCC by promoting proliferation, invasion, and metastasis through its targeting of the miR-491-5p/MMP9 axis. Therefore, this axis could represent a promising alternative therapeutic target for RCC treatment. [ABSTRACT FROM AUTHOR]

A pathological hallmark of Alzheimer's disease (AD) is the region-specific accumulation of the amyloid-beta protein (Aβ), which triggers aberrant neuronal excitability, synaptic impairment, and progressive cognitive decline. Previous works have demonstrated that Aβ pathology induced aberrant elevation in the levels and excessive enzymatic hydrolysis of voltage-gated sodium channel type 2 beta subunit (Navβ2) in the brain of AD models, accompanied by alteration in excitability of hippocampal neurons, synaptic deficits, and subsequently, cognitive dysfunction. However, the mechanism is unclear. In this research, by employing cell models treated with toxic Aβ1-42 and AD mice, the possible effects and potential mechanisms induced by Navβ2. The results reveal that Aβ1-42 induces remarkable increases in Navβ2 intracellular domain (Navβ2-ICD) and decreases in both BDNF exons and protein levels, as well as phosphorylated tropomyosin-related kinase B (pTrkB) expression in cells and mice, coupled with cognitive impairments, synaptic deficits, and aberrant neuronal excitability. Administration with exogenous Navβ2-ICD further enhances these effects induced by Aβ1-42, while interfering the generation of Navβ2-ICD and/or complementing BDNF neutralize the Navβ2-ICD-conducted effects. Luciferase reporter assay verifies that Navβ2-ICD regulates BDNF transcription and expression by targeting its promoter. Collectively, our findings partially elucidate that abnormal enzymatic hydrolysis of Navβ2 induced by Aβ1-42-associated AD pathology leads to intracellular Navβ2-ICD overload, which may responsible to abnormal neuronal excitability, synaptic deficit, and cognition dysfunction, through its transcriptional suppression on BDNF. Therefore, this work supplies novel evidences that Navβ2 plays crucial roles in the occurrence and progression of cognitive impairment of AD by transcriptional regulatory activity of its cleaved ICD. [ABSTRACT FROM AUTHOR]

Iron alloys, including steels and magnetic functional materials, are widely used in capital construction, manufacturing, electromagnetic technology, etc. However, they face the long-standing challenge of high coefficient of thermal expansion (CTE), limiting the applications in high-precision fields. This work proposes a strategy involving the in-situ formation of a nano-scale lamellar/labyrinthine negative thermal expansion (NTE) phase within the iron matrix to tackle this problem. For example, a model alloy, Fe-Zr10-Nb6, was synthesized and its CTE is reduced to approximately half of the iron matrix. Meanwhile, the alloy possesses a strength-plasticity combination of 1.5 GPa (compressive strength) and 17.5% (ultimate strain), which outperforms other low thermal expansion (LTE) metallic materials. The magnetovolume effect of the NTE phase is deemed to counteract the positive thermal expansion in iron. The high stress-carrying hard NTE phase and the tough matrix synergistically contribute to the high mechanical properties. The interaction between the slip of lamellar microstructure and the slip-hindering of labyrinthine microstructure further enhances the strength-plasticity combination. This work shows the promise of offering a method to produce LTE iron alloys with high mechanical properties. Iron alloys are essential but are limited by high thermal expansion. This work reports a strategy to reduce thermal expansion by in-situ forming negative thermal expansion phases within iron alloys, while maintaining high mechanical properties. [ABSTRACT FROM AUTHOR]

Key message: A total of 24 genes of vacuolar H+-translocating pyrophosphatases H+-PPases (VPP) genes were identified in Saccharum spontaneum AP85-441 and the ScVPP1-overexpressed Arabidopsis plants conferred salt tolerance. The vital role of vacuolar H+-translocating pyrophosphatases H+-PPases (VPP) genes involved in plants in response to abiotic stresses. However, the understanding of VPP functions in sugarcane remained unclear. In this study, a total of 24 VPP genes (SsaVPP1–SsaVPP24) were identified in the Saccharum spontaneum genome of haploid clone AP85-441. These genes were distributed in two phylogenetic groups. The SsaVPPs displayed diverse physio-chemical and gene structure attributes. The SsaVPP family genes have expanded through segmental duplication (20 gene pairs) rather than tandem duplication. A full-length cDNA of ScVPP1 was cloned from the sugarcane cultivar ROC22 and shared 99.48% sequence identity (amino acid) with homologous gene SsaVPP21 from AP85-441. In ROC22, the ScVPP1 gene was considerably upregulated by NaCl and ABA treatments among leaf, root, and stem tissues, while this gene was exclusively upregulated in the root with PEG treatment. Under NaCl and ABA stresses, yeast cells transfected by the ScVPP1 plasmid showed distinct growth rates compared to control yeast cells transfected by the empty vector. In transgenic Arabidopsis lines overexpressing ScVPP1, the seed gemination and survival rate were enhanced under NaCl treatment but not under ABA stress as compared to wild-type plants. These results suggested that the ScVPP1 gene conferred tolerance to slat and may be used as a salt resistance gene source for sugarcane breeding. [ABSTRACT FROM AUTHOR]

High performance 1–3 piezocomposite is crucial to high-frequency medical ultrasound imaging as its performance enhancement to an ultrasound transducer. A bandwidth enhancement effect had been found when a novel PZT-based short-fiber piezocomposite was fabricated and applied in the transducer. The electromechanical coupling coefficient kt of the short-fiber piezocomposite was as high as 63% at high frequency. An ultra-high bandwidth of the ultrasound transducer obtained to be 131.6% @-6 dB. The high performances of the piezocomposite were owing to the longitudinal vibration enhancement and lateral vibrations depression which were derived from the shape and randomized distribution of the ceramic pillars, respectively. It indicates that the PZT short-fiber piezocomposite is a promising candidate for commercial high-frequency medical ultrasound transducers. [ABSTRACT FROM AUTHOR]

The study of the pore size characteristics of porous materials and the concretization of the loss mechanism is important for the preparation of high-performance wave-absorbing materials. Hence, the carbon materials with 3D ordered macroporous (3DOM) structure were prepared by template method in this paper. 3DOM structured carbon materials with different pore size characteristics were constructed by varying the particle size of template spheres. The amount of heterogeneous interfaces between carbon/air varies greatly among carbon materials with different pore sizes due to the difference in specific surface area, leading to different interfacial polarization, which in turn modulates the dielectric constant and impedance matching of the materials and enhances the wave-absorbing performance. The 3DOM RF-300 material with an aperture of 300 nm obtains the effective absorption bandwidth of 4.8 GHz and the strongest reflection loss of − 42.33 dB. In addition, based on the simulation level, the material loss mechanism to electromagnetic waves is investigated. Meanwhile, the practical application capability of the material is demonstrated by the radar scattering cross-sectional area simulation of 3DOM RF-300 material. The study provides a new path for designing high-performance wave absorbers based on material structure design and simulation techniques. [ABSTRACT FROM AUTHOR]

Domain adaptive object detection (DAOD) is an effective approach to solving the domain shift problem, which aims to improve the generalization ability on the target domain through joint training with labeled source domain and unlabeled target domain data. However, in the real world, the source domain is often inaccessible due to privacy, legal, and regulatory reasons. Source-free object detection (SFOD) adapts a well-trained source domain object detector to the target domain without needing access to source domain data. Most existing SFOD methods are based on a self-training framework (such as the teacher–student framework), where the teacher model guides the student model’s training by setting a confidence threshold to filter out unreliable pseudo-labels. However, this may lead to the loss of semantic information in the target domain, resulting in suboptimal model performance. Therefore, in this paper, we propose a contrastive learning framework guided by proposal-level reliable feature guidance. Specifically, we first build a general self-training framework based on Faster-RCNN. Then, we introduce a novel proposal-level pseudo-label annotation and filtering method (PAF), improving the annotation and filtering of pseudo-labels and obtaining proposal-level reliable features. Next, we design reliable feature banks to categorize and store reliable proposal features. Finally, we propose classification contrastive learning (CCL) and bounding box contrastive learning (BCL) to further extract semantic information from reliable proposal features, learning the lost semantic information in the target domain. Extensive experiments on seven benchmark datasets demonstrate the effectiveness of our method. [ABSTRACT FROM AUTHOR]

Acute liver failure (ALF) is a life-threatening clinical syndrome characterized by high-grade inflammation and multi-organ failure. Our previous study shows that targeting the M2 isoform of pyruvate kinase (PKM2) to inhibit macrophage inflammation may be a promising strategy for ALF treatment. however, the mechanism by which PKM2 regulates the inflammatory response is unclear. Here we demonstrate that PKM2 contributes to ALF by modulating NLRP3-mediated pyroptosis activation in liver macrophages. The specific knockout of PKM2 in myeloid cells reduces mortality and alleviates hepatic injury in D-galactosamine/LPS-induced ALF mice. Single-cell transcriptome analysis suggests that NLRP3 inflammasome activation of macrophages involves in ALF, knockout of PKM2 in macrophages reduces the expression of NLRP3, and activation of pyroptosis. Pharmacological inhibition of the PKM2 nuclear translocation, but not glycolytic activity, protects mice from ALF. Pharmacological and genetic inhibition of PKM2 attenuates NLRP3-mediated pyroptosis activation and consequently reduces the release of IL-1β and IL-18 by macrophages. Mechanistically, PKM2 translocates into the nucleus and combines with STAT3, enhancing its phosphorylation and recruitment to the NLRP3 promoter region, thereby increasing NLRP3 expression. This work defines PKM2 acts as an important nonmetabolic regulator of NLRP3 that modulates pyroptosis activation in macrophages and guides future therapeutic strategies development for ALF. PKM2 acts as a critical nonmetabolic regulator of macrophage pyroptosis by increasing NLRP3 expression promoting NLRP3 inflammasome activation via nuclear translocation and enhancing STAT3 phosphorylation during acute liver failure. [ABSTRACT FROM AUTHOR]

The incompatibility of the large piezoelectric response (d33) and high depolarization temperature (Td) in lead-free piezoelectric ceramics limited their practical applications. The most used modification methods for improving d33 or Td commonly required a delicate control of complex compositions. Here, a strategy for simply changing the sintering temperature is used to defer the Td and increase d33 simultaneously. The Td and d33 of unmodified Bi0.5Na0.5TiO3-0.2Bi0.5K0.5TiO3 (BNKT20) ceramics increase with increasing sintering temperature until both of them reach the maximum (d33 ~ 174pC/N, Td ~ 177 °C) at the sintering temperature of 1100 °C. In-depth analysis unveils the critical role of multiphase coexistence and oxygen vacancies in enhancing Td by optimizing sintering temperature. Meanwhile, increasing sintering temperature promotes large grain size with easy domain orientation, thus, yielding the improved d33. This work provides a simple and effective method to broaden the working range of Bi0.5Na0.5TiO3-based (BNT) piezoelectric ceramics at high temperature under the premise of realizing high piezoelectric properties. [ABSTRACT FROM AUTHOR]

Background: The total burden of migraine includes not only the episodes with headache pain but extends throughout the interictal periods. Interictal symptoms and associated psychological responses may profoundly impact well-being and drive treatment-seeking behavior. Methods: A cross-sectional online survey was conducted with participants aged ≥ 18 years, 250 with episodic migraine (EM) and 250 with chronic migraine (CM), having ≥ 4 monthly migraine headache days. All were naïve to galcanezumab or began ≤ 6 months before survey completion. The study evaluated factors associated with the Migraine Interictal Burden Scale (MIBS-4), including social determinants of health and well-being. Multiple linear regression, logistic regression, and random forests (RF) were used to explore predictors of MIBS-4. Results: The majority of participants (90%) were female with a mean (standard deviation) age of 40.6 (± 12.0) years and 18.1 (± 12.7) years since the first migraine episode. Sociodemographically, the EM and CM groups were similar. Common comorbidities were anxiety disorder (45%) and depression (44%). Migraine family history was reported in 59% of participants. MIBS-4 was correlated with a number of diverse variables, including well-being, anxiety sensitivity, income, aura symptoms, and the worst migraine pain in the year before starting galcanezumab. Linear and logistic regression identified years since the first symptom, worst migraine attack pain, premonitory symptoms, and income as significant predictors. RF explained more of the variance than multiple linear regression and introduced additional concepts to the prediction of MIBS, identifying well-being (WHO-5 total score), the WHO-5 item "cheerful and in good spirits," worry about exercise, and fear of missing social obligations as significant predictors. Socioeconomic status and income were also critical explanatory variables for interictal burden (IIB) based on regression modeling and RF. Still, income was the only variable significantly associated with IIB across regression and RF methods. Conclusions: Interictal burden should be considered in the medical care of people with migraine. This additional burden is holistic, with psychosocial and socioeconomic elements in addition to residual symptoms. It is essential to consider this when assessing the impact of IIB. [ABSTRACT FROM AUTHOR]

Co-pyrolysis, an upgrading thermochemical conversion technology, has the proven potential to be a convenient and efficient route for the conversion of biomass wastes into bio-energy products. The study aimed to investigate the effects of the amount of polystyrene (PS) (10 and 50%) and the pyrolysis temperature (400, 500, and 600 °C) on the properties of biochars obtained through the co-pyrolysis of Stevia rebaudiana straw (SRS) and PS in a fixed-bed reactor. Thermogravimetric analysis indicated that co-pyrolysis could delay the thermal degradation of PS, but accelerate the degradation of SRS. The addition of PS has a positive effect on the biochar yield due to the synergistic effects of the PS and SRS co-pyrolysis. Furthermore, the volatile matter and oxygen contents of co-pyrolytic biochars were found to be reduced, while the carbon content, fixed carbon, higher heating value, and energy density were increased. With increasing in the PS content at 500 and 600 °C, the fuel ratio increased significantly from 1.78 and 2.21 to 2.55 and 2.89, respectively, while the trend was the opposite at 400 °C. The fuel quality of co-pyrolytic biochars prepared at 500 and 600 °C is close to those of bituminous and anthracite, respectively. For use as a solid fuel, biochars produced from co-pyrolysis with a low level of PS addition (10%) at 500/600 °C are more suitable. The results from this study provided some insights into the biomass and plastics wastes recycling to generate value-added biochar products. [ABSTRACT FROM AUTHOR]

The development of porous carbon materials with high CO2 adsorption capacity is crucial for addressing the current issues of industrial air pollution and global warming. In this study, B/N codoped porous carbon materials were prepared via a combined strategy involving the use of a self-sacrificing template in conjunction with potassium hydroxide activation; moreover, g-C3N4 was used as the N source and boric acid was used as the B source. The pore structure and surface chemistry were investigated in detail using different techniques such as X-ray diffraction, scanning electron microscopy, N2 adsorption and desorption, transmission electron microscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy. Results showed that the prepared material exhibited the highest specific surface area (2278 m2/g) and pore volume (1.00 cm3/g) when the ratio of B/N sources was 1:0.5; moreover, its CO2 adsorption value (3.26 mmol/g) was higher than those of most codoped adsorbents. [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP) is a protein made by the liver, which is released into the bloodstream in response to inflammation. Furthermore, CRP is a potential risk factor for heart disease. Hence, it is of great importance to develop a rapid, sensitive, accurate, and cost-effective method for CRP detection. Herein, we report an enzyme-free fluorescent assay for the rapid and ultra-sensitive detection of CRP with a limit of detection (LOD) reaching as low as 3.08 pg/mL (i.e., ~ 27 fM). The high sensitivity of our method was simply achieved via dual-functionalized gold nanoparticles (AuNPs). By regulating the molar ratio of DNA to CRP antibody immobilized on the AuNP surface, hundreds to thousands-fold amplification in the analyte signal could be instantly accomplished. Furthermore, our sensor was selective: non-target proteins such as interleukin-6, interleukin-1β, procalcitonin, bovine serum albumin, and human serum albumin did not interfere with the target CRP detection. Moreover, simulated serum samples were successfully analyzed. Given the excellent sensitivity, selectivity, and high resistance to complicated matrices, the enzyme-free CRP detection strategy developed in this work can be used as a generic platform to construct sensors for a wide variety of protein biomarkers and hence offers potential as a tool for rapid, accurate, and low-cost medical diagnosis. [ABSTRACT FROM AUTHOR]

Quiescent cells require a continuous supply of proteins to maintain protein homeostasis. In fission yeast, entry into quiescence is triggered by nitrogen stress, leading to the inactivation of TORC1 and the activation of TORC2. In this study, we demonstrate that the Greatwall-Endosulfine-PPA/B55 pathway connects the downregulation of TORC1 with the upregulation of TORC2, resulting in the activation of Elongator-dependent tRNA modifications crucial for sustaining the translation programme during entry into quiescence. This mechanism promotes U34 and A37 tRNA modifications at the anticodon stem loop, enhancing translation efficiency and fidelity of mRNAs enriched for AAA versus AAG lysine codons. Notably, several of these mRNAs encode TORC1 inhibitors, TORC2 activators, tRNA modifiers, and proteins necessary for telomeric and subtelomeric functions. Therefore, we propose a mechanism by which cells respond to nitrogen stress at the level of translation, involving a coordinated interplay between tRNA epitranscriptome and biased codon usage. This study describes a pathway in fission yeast that senses nutrient levels and maintains protein homeostasis during starvation by modifying tRNAs in the anticodon loop. These modifications enhance the translation of critical AAA-rich mRNAs, promoting gene silencing and the long-term survival of quiescent cells. [ABSTRACT FROM AUTHOR]

Context: Based on the density functional theory (DFT), we analyzed the changes of the FOX-7 molecule under external electric field (EEF) from multiple perspectives, including molecular structure, electronic structure, decomposition mechanism, frontier molecular orbitals (FMOs), and density of states (DOS). The results revealed that as the intensity of the positive EEF increased, the detonation performance of the FOX-7 molecule was significantly enhanced, while its thermal stability was also improved. This discovery challenges the traditional concept that explosives are inherently dangerous under external electric fields and provides new insights for research in related fields. To further explore the impact of EEF on the thermal stability of FOX-7, we conducted a thorough analysis of the mechanism by which EEF affects the decomposition process. Our findings indicate that applying a positive EEF significantly increases the energy required to overcome intramolecular hydrogen transfer and C-NO2 bond rupture, while having a relatively minor effect on the nitro isomerization process. This observation further demonstrates that the appropriate application of a positive EEF can enhance the detonation performance of FOX-7 without compromising its thermal stability. Further research revealed that as the intensity of the positive EEF increased, the electronegativity of the nitro group gradually enhanced, leading to an increase in the electronegativity of the oxygen atoms within it. This made the oxygen atoms more prone to participating in chemical reactions. This phenomenon also explains why the energy barrier required for nitro isomerization in FOX-7 gradually decreases as the intensity of the positive EEF increases. Methods: Based on the density functional theory (DFT), the structural optimizations were performed both under applied EEF and without EEF at the B3LYP/6-311G (d, p) level. All optimized results were converged and exhibited no imaginary frequencies. Based on the optimized structures, single-point energy calculations were further conducted at the B3LYP/def2-TZVPP level. Subsequently, analyses of molecular structure, electronic structure, decomposition mechanism, frontier molecular orbitals, and density of states were carried out. [ABSTRACT FROM AUTHOR]

The purpose of the study was to introduce a novel surgical approach of combining laparoscopic pyelotomy with ultrasonic lithotripsy via a nephroscope for the treatment of complex renal stones. Between May 2021 and April 2023, 32 patients underwent laparoscopic pyelotomy combined with ultrasonic lithotripsy via a nephroscope and their perioperative variables were retrospectively collected and outcomes were assessed. Dissection and incision of the anterior renal pelvis wall was performed via a laparoscope. A 19.5 F nephroscope was introduced into the renal pelvis through a laparoscopic trocar from the incision. Stones were fragmented and sucked out using a 3.3 mm ultrasonic probe placed through the nephroscope. All operations were completed successfully and the stone-free rate at 3 days after operation was 87.5% (28/32). Four (12.5%, 4/32) patients with staghorn stones had a small residual stone in the lower calyx after operation and did not require reintervention. No patient required perioperative transfusion and four (12.5%, 4/32) patients with struvite stones developed postoperative fever, which was successfully treated with intravenous antibiotics. The mean follow-up time was 14.0 ± 7.2 months, with no patient developing long-term complications. This approach offers a safe and effective treatment option for complex renal stones, as the method exhibits a high clearance rate with few complications. [ABSTRACT FROM AUTHOR]

Small and medium enterprises (SMEs) in supply chains often struggle to obtain external financial resources from banks, due to their poor supply chain visibility. Prior studies suggest that adopting blockchain technology can enhance supply chain visibility, thus facilitating access to supply chain finance (SCF). In this study, we compare the traditional SCF mode with the blockchain-enabled SCF mode within the framework of a dual-channel closed-loop supply chain (CLSC). Our analysis incorporates both prepayment financing and accounts receivable financing or purchase order financing into the analytical model. Our main findings are as follows. Firstly, adopting blockchain technology leads to a reduction in the interest rate, enabling the manufacturer and the retailer to raise their buy-back prices. This increase in buy-back prices subsequently encourages greater recycling of used products. Secondly, in a context marked by high cross-price elasticity, we observe abrupt pricing fluctuations in both online and offline sales channels. However, adopting blockchain technology can effectively mitigates these fluctuations, thus ensuring the sustained stability of demand in both sales channels. Thirdly, in the blockchain-enabled mode, equilibrium wholesale price, offline sales price, manufacturer's buy-back price, and retailer's buy-back price are higher compared to those in the traditional mode. Conversely, the equilibrium direct sales price is lower in the blockchain-enabled mode than in the traditional mode. Fourthly, changes in interest rates and cross-price elasticity have analogous impacts on pricing dynamics in both the traditional and blockchain-enabled modes. Fifthly, adopting blockchain technology leads to an all-win outcome for participants in SCF arrangements only when the benefits of blockchain-enabled traceability and reduced interest rates outweigh the costs associated with hosting and access. [ABSTRACT FROM AUTHOR]

Phytophthora pathogens secrete numerous apoplastic effectors to manipulate host immunity. Herein, we identified a polysaccharide lyase 1 protein, PsPL1, which acts as an essential virulence factor of P. sojae infection in soybean. However, the overexpression of PsPL1 in P. sojae reduced infection and triggered enhanced immune responses in soybean. PsPL1 exhibited pectin lyase activity and degraded plant pectin to generate pectin oligosaccharides (POSs) with a polymerization degree of 3–14, exhibiting different levels of acetylation and methylation modifications. PsPL1 and the degraded pectin products triggered immune responses in soybean and different Solanaceous plants. The PsPL1-triggered immune responses required RSPL1, a membrane-localized leucine-rich repeat receptor-like protein, which is essential for Phytophthora resistance. Conversely, the PsPL1-degraded product-triggered immune responses depended on the membrane-localized lysin motif receptor-like kinase CERK1. This study reveals that the pectin lyase exhibits a dual immunogenic role during P. sojae infection, which activates plant resistance through different immune receptors and provides novel insights into the function of pectin lyase in host-pathogen interactions. [ABSTRACT FROM AUTHOR]

High-capacity silicon anode is one of the ideal anode materials for the next generation, but the volume expansion effect and low conductivity hinder its development. In this study, a simple and low-cost method was employed to prepare micron-sized silicon raw materials. Subsequently, a hard carbon-coated structure was combined with the metal modification method to successfully prepare hard carbon–coated silver-modified silicon particle material. Due to the hard carbon coating structure, Si/Ag@HC materials can effectively alleviate the volume expansion of silicon, and the modification of metallic silver can not only improve the conductivity of silicon, but also further enhance the ability to limit the volume expansion effect. The Si/Ag@HC maintains a specific capacity of 997.05 mAh g−1 after 200 cycles at a current density of 0.5C, and it also shows an excellent rate performance of over 600 mAh g−1 at a current density of 2C. [ABSTRACT FROM AUTHOR]

In our previous work (Powder Technol, 2024, 433, 119276), an approach of inclined bottom blowing has been proposed. It was found that this novel mode of bottom blowing helps to improve the flow characteristics and mixing effect of bath in bottom blowing converters. In this work, the possibility of applying this bottom blowing technique in top and bottom combined blowing converters is investigated. An Euler-Euler model is adopted to describe top and bottom blown process in a simplified model of a 260 t converter. The accuracy of the model is validated by comparing the numerical simulation results with the previously published experimental results. Then, according to the similarity theory, the size of an actual converter is downsized and based on the downsized model a series of numerical simulations are carried out. The influence of bottom blowing angle on the flow characteristics, mixing efficiency and converter wall erosion are discussed in detail. Numerical simulation results show that the mixing time first decreases and then increases with the increase of the bottom blowing angle. When the bottom blowing angle is 5~6 deg, the mixing time of molten pool is the shortest because the flow dynamics in the lower part of the bath are effectively improved by using the 6 deg angle for bottom blowing. The wall shear stress is used to characterize the erosion of the converter wall. The study results show that the most severe area of erosion on the converter wall occurs near the liquid surface in the direction of the top jet. The severity of erosion on the converter wall decreases gradually as the bath depth increases. The wall shear stress changes slightly with the angle, which indicates that the novel bottom blowing approach will not aggravate the wall erosion. Combining with the results in this paper and the factory production demand, the actual industrial converter using the 7 deg bottom blowing angle effectively improve the efficiency of smelting. [ABSTRACT FROM AUTHOR]

Heritable endosymbionts widely occur in arthropod and nematode hosts. Among these endosymbionts, Wolbachia has been extensively detected in many arthropods, such as insects and crustaceans. Maternal inheritance is the most basic and dominant mode of transmission of Wolbachia, and it might regulate the reproductive system of the host in four ways: feminization, parthenogenesis, male killing, and cytoplasmic incompatibility. There is a relatively high percentage (10%) of thelytokous species in Oribatida, a suborder under the subclass Acari of arthropods, but the study of the endosymbionts in oribatid mites is almost negligible. In this paper, we detected endosymbiotic bacteria in two parthenogenetic oribatid species, Nothrus anauniensis Canestrini and Fanzago, 1877, which has never been tested for endosymbionts, and Oppiella nova, in which Wolbachia and Cardinium have been reported before. The results showed that Wolbachia was first found in N. anauniensis with an infection rate of 100% across three populations. Phylogenetic analysis showed that Wolbachia in N. anauniensis belonged to the supergroup K, marking the second supergroup of Wolbachia found in oribatid mites. Unlike previous studies, our study did not detect Wolbachia in O. nova, leading to the exclusion of Wolbachia's role in mediating thelytoky in this species. [ABSTRACT FROM AUTHOR]

A 90-day feeding trial was conducted to evaluate the effects of replacing dietary fishmeal (FM) with defatted black soldier fly larvae meal (BSFL) on the growth performance and fillet quality of largemouth bass (Micropterus salmoides). The largemouth bass was divided into six groups (BSFL0, BSFL15, BSFL30, BSFL45, BSFL75, and BSFL100) and fed six isonitrogenous(CP 50%, 508 g/kg) and isolipid (CL 9%, 124 g/kg) diets, in which 0, 15%, 30%, 45%, 75%, and 100% of the fishmeal was replaced with BSFL, respectively. The results showed that the final body weight (FBW) and specific growth rate (SGR) of the largemouth bass decreased with increasing BSFL content, and they were significantly lower in BSFL75 than in BSFL0. The weight gain rate (WGR) decreased with increasing BSFL content and the feed conversion ratio (FCR) of largemouth bass increased with increasing BSFL content. The saturated fatty acids (SFAs) and n-3 polyunsaturated fatty acids (PUFA) contents of the largemouth bass fillet significantly decreased, and the n-6 PUFA content of the largemouth bass fillets significantly increased with increasing dietary BSFL. The fillet b* significantly decreased with increasing BSFL content. The biological parameters, fillet proximate nutrient composition, fillet amino acid composition, skin color, and fillet texture of the largemouth bass were not affected by the replacement of BSFL. Transcriptomic analysis revealed that BSFL replacement of FM affects the immune system and metabolic processes of largemouth bass through signaling pathways such as complement and coagulation cascades, the PPAR signaling pathway, cholesterol metabolism, and fat digestion and absorption. In conclusion, a replacement level lower than 45% BSFL was suggested for the overall growth and fillet quality of largemouth bass. [ABSTRACT FROM AUTHOR]

This is a single Institute, prospective cohort study. We enrolled twenty-two postmenopausal women with pelvic organ prolapse planning to undergo vaginal hysterectomy with transvaginal pelvic reconstructive surgery, with or without a concomitant anti-incontinence procedure. Vaginal swabs and urine samples were longitudinally collected at five time points: preoperative consult visit (T1), day of surgery prior to surgical scrub (T2), immediately postoperative (T3), day of hospital discharge (T4), and at the postoperative exam visit (T5). Women experiencing urinary tract infection symptoms provided a sample set prior to antibiotic administration (T6). Microbiome analysis was performed on vaginal and urinary specimens at each time point. Region V3-V5 of the 16S ribosomal RNA gene was amplified and sequenced. DNA samples were analyzed for visit T1, T2, T5 and T6. Six (27.3%) participants developed postoperative urinary tract infection whose vaginal sample at first clinical visit (T1) revealed beta-diversity analysis with significant differences in microbiome structure and composition. Women diagnosed with a postoperative urinary tract infection had a vaginal microbiome characterized by low abundance of Lactobacillus and high prevalence of Prevotella and Gardnerella species. In our cohort, preoperative vaginal swabs can predict who will develop a urinary tract infection following transvaginal surgery for pelvic organ prolapse. ClinicalTrials.gov Identifier: NCT02751073. [ABSTRACT FROM AUTHOR]

Intermittent fasting has been shown to alleviate stress, anxiety, and depressive symptoms. Although noradrenaline, also known as norepinephrine (NE), is implicated in stress regulation, the dynamics of NE release and the associated neural pathways during stress coping behaviors in fasting mice remain poorly understood. In this study, we employed the forced swimming test (FST) to evaluate the effects of intermittent fasting on stress coping behavior in mice. Our results demonstrate that mice subjected to long-term intermittent fasting exhibited significantly more active coping behaviors in the FST compared to control mice. In contrast, acute fasting did not produce similar effects. Using the fluorescent GRAB-NE sensor to measure NE release with sub-second temporal resolution during the FST, we found that intermittent fasting modulates the locus coeruleus-medial prefrontal cortex (LC-mPFC) pathway, which underlies these behavioral adaptations. Moreover, chemogenetic activation of LC-mPFC projections strongly promoted active coping in the FST. These findings suggest that enhanced LC-mPFC activity mediates the increased active coping behavior observed in fasting mice. This study provides new insights into the neural mechanisms through which intermittent fasting may ameliorate depressive-like behaviors, offering potential therapeutic targets for stress-related disorders. [ABSTRACT FROM AUTHOR]

In this study, hollow nanoflower spherical Cu9S8 and Cu9S8/Fe3O4@BC with adsorption and antibacterial properties was prepared by coprecipitation and solvothermal method, respectively. The adsorption results showed that the Cu9S8 exhibited excellent adsorption performance on sulfonamide antibiotics (SAs), especially for sulfamethoxazole (SMZ). The optimal addition amount of Cu9S8 is 0.2 g, which results in a maximum adsorption capacity of 33.4 mg/g for SMZ within 120 min. The fitting results of adsorption and desorption kinetics and thermodynamics, as well as the conditions such as pH value and ionic strength were compared. It was found that different interactions led to the differential adsorption of SAs by Cu9S8. The desorption experiment further elucidated its adsorption mechanism. The large desorption capacity indicates that SAs on Cu9S8 can be further recovered and treated. The auto-deposition characteristics of Cu9S8 and the hysteresis loop of Cu9S8/Fe3O4@BC were studied to effectively recover Cu9S8 from aquatic environments. Additionally, more than 99% of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were exterminated by Cu9S8 and Cu9S8/Fe3O4@BC within 20 min. The above results suggested that the hollow nanoflower spherical Cu9S8 and Cu9S8/Fe3O4@BC composite materials can provide a new strategy for solving pollution problems and waste treatment. [ABSTRACT FROM AUTHOR]

The intermittency and randomness of photovoltaic power present different characteristics due to seasonal variations, which greatly affects the reliability of power supply. To boost the prediction accuracy of photovoltaic power, a short-term prediction combination model named GSK–BiGRU–XGboost is proposed. First, the Pearson correlation coefficient is adopted to determine highly-correlated meteorological factors to photovoltaic power to construct the input features. Second, the prediction errors of different single models are compared, and the two, i.e., Bidirectional Gated Recurrent Unit (BiGRU) and Extreme Gradient Boosting (XGboost) that have the smallest errors and lowest correlation are selected to construct the combination model. Third, to achieve an appropriate weight coefficient of the model, an improved gaining sharing knowledge-based algorithm (GSK) based on parameter adaption is designed to optimize it effectively. Fourth, seasonal models and year-round model based on GSK–BiGRU–XGboost are compared to reveal the effect of seasonal characteristics. Finally, the influence of historical meteorological data window with different steps is investigated. To verify the performance of GSK–BiGRU–XGboost, it is compared with different single and combination models under different weather conditions. GSK–BiGRU–XGboost achieves a high prediction accuracy of 97.85%, which is 9.46% and 12.43% higher than its member models, respectively. Besides, GSK can lead to a 1.71% improvement in the accuracy. [ABSTRACT FROM AUTHOR]

A comprehensive evaluation was conducted using several investigative techniques to understand the corrosion characteristics and underlying mechanisms of 2A97 Al–Li alloy exposed to a marine atmosphere. These techniques included salt-spray (3.5 wt.% NaCl and 0.1 wt.% Na2SO4) assaying, gravimetric assessment of corrosion loss, macro- and microscopic morphological evaluations, x-ray photoelectron spectroscopic analysis, and electrochemical assessments. The study findings showed a declining trend for the corrosion propensity of the 2A97 Al–Li alloy. The accumulated corrosion by-products predominantly comprised compounds such as Al2O3 and Al(OH)3, complemented by trace constituents such as Li2O, LiOH, Li2CO3, Al-based chlorides and sulphates, and elemental Cu. Notably, the Al2O3 present in the corrosion by-product stratum exhibited considerable compactness, thereby curtailing the permeation of corrosive ions. Concurrently, the stable Li2CO3 film exhibited excellent corrosion-inhibition properties. The cyclic dissolution and reprecipitation of elemental Cu bolstered the adhesive strength between the corrosion product layer and alloy substrate, further mitigating the corrosion kinetics of the foundational material. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the association between the triglyceride-glucose (TyG) index and high-sensitivity C-reactive protein-to-albumin ratio (hsCAR) and the prognosis of patients with STEMI and hypertension. A total of 699 patients diagnosed with STEMI and hypertension were included in this study database. Compared to the low TyG index group (< 7.8), the high TyG index group (≥ 7.8) was associated with an increased risk of MACE (HR 2.09, 95% CI = 1.58–2.77; P < 0.001). Similarly, a higher hsCAR (≥ 0.15) was linked to an increased risk of MACE (HR 1.46, 95% CI = 1.12–1.90; P = 0.005). Subsequently, we categorized the population into four groups based on the defined cutoff points. Compared to the low TyG–low hsCAR subgroup, the other three subgroups demonstrated an elevated risk of MACE. Among patients treated with PCSK9 and SGLT2 inhibitors, the combined effect of the TyG index and hsCAR on MACE was attenuated. Finally, The combined TyG index and hsCAR model exhibited optimal performance (AUC = 0.71, 95% CI = 0.67–0.75; P < 0.001). This study demonstrates that the TyG index and hsCAR provide strong combined predictive power. The synergistic utilization offers a comprehensive approach to cardiovascular risk assessment. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is one of the most important health problems among elderly men in China, with the increasing aging of the population. A cross-sectional survey was conducted in eastern China from 2022 to 2023. Recruitment included a total of 70,342 participants aged 60 or older. Social demographic information, such as individual factors like age, education levels and behavior habits, physical examination and laboratory tests results were collected. Age-standardized prevalence rates were estimated by a direct method with a standard population. T test and chi-square test were used to compare the statistical differences. Multivariate regression models were used to identify the risk factors of PCa. Overall, the crude and age-standardized PCa prevalence is 0.93% and 0.91%, respectively in eastern China. When we adjusted all the co-variables, it showed that high age, smoking, having a higher BMI and higher CA19-9 were associated with a higher risk for a prostate cancer diagnosis. Faced with the demographic transition, innovative strategies are needed to control and prevent PCa. Conducting early screening among male population in community health service centers in eastern of China, especially among a population with associated risk factors such as high age, obesity, and conducting community-based intervention programs might be helpful to address this increasingly significant health problem. [ABSTRACT FROM AUTHOR]

Objective: To compare efficacy of proximal and distal laparoscopic ureteroureterostomy (UU) for complete duplex kidneys in children. Methods: Patients who underwent laparoscopic UU for complete duplex kidneys between December 2016 and July 2022 were reviewed retrospectively. 71 patients who had normal lower pole moiety without vesicoureteral reflux (VUR) were recruited. All of them underwent ultrasound, voiding cystourethrography (VCUG), renal scintigraphy, and magnetic resonance urography preoperatively. Proximal laparoscopic UU was performed in 35 patients and distal laparoscopic UU in 36 patients. Double J stents were placed in normal lower pole moieties. Clinical data, including general information, diagnosis, surgical management, imaging characteristics, clinical symptoms and postoperative complications (classified according to the modified Clavien–Dindo classification), and length of stay were recorded. Measurement date comparisons between groups were performed by t test, counting date were analyzed by chi-square test. Results: The study consisted of 71 patients (56 females and 15 males) with complete duplex kidneys (41 in left kidney and 30 in right kidney). The patients' mean age was 34 m (range 3–161 m) and follow-up ranged from 25 to 81 m. No significant difference was found in age and follow-up time between the two groups. Laparoscopic UU was performed in all patients successfully. The operation time of the two groups was 108.42 ± 26.95 min for distal UU vs 121.46 ± 35.15 min for proximal UU(p = 0.14). No significant difference in postoperative complications was seen between the two groups (22.2% vs 31.4%, p = 0.345). However, in terms of the grading of postoperative complications, the proximal UU group had a higher grade (3 of them had a grade of IV) and more serious complications. Conclusions: There was no significant difference in the overall incidence of complications between distal and proximal UU. Compared with proximal laparoscopic UU, distal laparoscopic UU is easier to perform with less injury to the peripheral tissues. Postoperative complications of proximal UU are more serious and more difficult to manage. We recommend complete duplex kidney ureteral reconstruction with distal UU. [ABSTRACT FROM AUTHOR]

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Introduction: We aim to evaluate the efficacy and safety of pioglitazone/metformin fixed-dose combination (FDC) versus uptitrated metformin in patients with type 2 diabetes mellitus (T2DM) without adequate glycemic control. Methods: A total of 304 patients were recruited from 15 hospitals in China and randomly assigned (1:1) to the test group (pioglitazone/metformin FDC, 15/500 mg) or the control group (uptitrated metformin, 2000–2500 mg/day). The primary endpoint was the proportion of patients with glycated hemoglobin A1c (HbA1c) ≤ 6.5% and ≤ 7.0% at week 16. The secondary outcomes included the change from baseline in glucose, serum lipids, and liver function. Full analysis set (FAS) and per-protocol set (PPS) were used for analyses. Results: In the test group, 103 (69.59%) patients reached HbA1c ≤ 7.0% (FAS, P = 0.009), with 68 (45.95%) patients achieved HbA1c ≤ 6.5 (FAS, P = 0.043). More reduction in HbA1c, homeostatic model assessment for insulin resistance, and diastolic pressure was found. Bodyweight, body mass index, and high-density lipoprotein cholesterol increased markedly. The changes of triglycerides, alanine transaminase, aspartate aminotransferase, and high-sensitivity C-reactive protein decreased noticeably. There were no significant differences in rates of adverse events between the two groups. Conclusions: Pioglitazone/metformin FDC was superior to uptitrated metformin among patients with T2DM without adequate glycemic control. Trial Registration Number: This trial is registered with the Chinese Clinical Trial Registry (ChiCTR1900028606). [ABSTRACT FROM AUTHOR]

Understanding the maintenance and shift in reproductive strategies is a fundamental question in evolutionary research. Although many efforts have been made to compare different reproductive strategies, the association between reproductive strategies and lineage divergence is largely unknown. To explore the impact of different reproductive strategies on lineage divergence, we investigated the evolution of clonality in Saxifraga sect. Irregulares+Heterisia. By integrating several lines of evidence, we found that the loss of clonality in Irregulares+Heterisia was associated with a progressive increase in diversification rate and intraspecific morphological diversity but with a reduction in species distribution range. Our findings provide insights into the ecological and evolutionary effects of different reproductive strategies, suggesting the necessity of integrating clonality into ecological and evolutional research. [ABSTRACT FROM AUTHOR]

In this paper, we conducted the axial compression test on one improved welded concrete filled L-shaped steel tube (IWCFLST) stub column and two stirrup-enhanced IWCFLST stub columns. The experimental results indicate that the stirrup-enhanced IWCFLST stub columns exhibit better compressive mechanical properties. The stirrups can increase the axial compressive load-bearing capacity by up to 35% and the ductility coefficients by 77%. The impact of the equivalent stirrup ratio on the axial compression mechanical behavior was investigated. Three-dimensional (3D) solid finite element (FE) model of the specimens was constructed by ABAQUS. Parametric analysis was performed and the restriction action of IWCFLST stub column under axial compression was studied. The numerical study revealed the working mechanism of stirrups, steel tubes on concrete, while direct confinement of concrete elevates its axial stress level. Considering the shape and the stirrups, the axial compression ultimate load-bearing capacity design method of the IWCFLST stub column was proposed, providing data support for the promotion and application of special-shaped CFST columns. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to describe the clinical features, diagnostic and therapeutic course of a patient with MODY13 caused by KCNJ11 (c.101G > A, p.R34H) and how it contributes to the pathogenesis of MODY13, and to explore new therapeutic targets. Methods: Whole-exome sequencing was used to screen prediagnosed individuals and family members with clinically suspected KCNJ11 mutations. Real-time fluorescence quantitative PCR, western blotting, thallium flux of potassium channels, glucose-stimulated insulin secretion (GSIS), and immunofluorescence assays were used to analyze the regulation of insulin secretion by the KCNJ11 mutant in MIN6 cells. Daily blood glucose levels were continuously monitored for 14 days in the proband using the ambulatory blood glucose meter (SIBIONICS). Results: Mutation screening of the entire exon of the gene identified a heterozygous KCNJ11 (c.101G > A, p.R34H) mutation in the proband and his mother. Cell-based GSIS assays after transfection of MIN6 using wild-type and mutant plasmids revealed that this mutation impaired insulin secretory function. Furthermore, we found that this impaired secretory function is associated with reduced functional activity of the mutant KCNJ11 protein and reduced expression of the insulin secretion-associated exocytosis proteins STXBP1 and SNAP25. Conclusion: For the first time, we revealed the pathogenic mechanism of KCNJ11 (c.101G > A, p.R34H) associated with MODY13. This mutant can cause alterations in KATP channel activity, reduce sensitivity to glucose stimulation, and impair pancreatic β-cell secretory function by downregulating insulin secretion-associated exocytosis proteins. Therefore, oral sulfonylurea drugs can lower blood glucose levels through pro-insulinotropic effects and are more favorable for patients with this mutation. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the efficacy and underlying mechanism of the mitochondrial fusion promoter M1 in mitigating cigarette smoking (CS)-induced airway inflammation and oxidative stress both in vitro and in vivo models. Methods: Cigarette smoke extract (CSE)-treated airway epithelial cells (BEAS-2B) and CS-exposed mice were pretreated with M1, followed by the measurement of proinflammatory cytokines, oxidative stress, mitochondrial fusion proteins (MFN2 and OPA1) and fission proteins (DRP1 and MFF). Molecular pathways were elucidated through transcriptomic analysis and Western blotting. Results: M1 pretreatment in CSE-treated cells significantly reduced the release of inflammatory cytokines (interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)–α); reduced malondialdehyde (MDA) and reactive oxygen species (ROS) levels; increased superoxide dismutase (SOD) activity; protected mitochondrial function by increasing the expression of mitochondrial fusion proteins (MFN2 and OPA1) and decreasing the expression of mitochondrial fission proteins (DRP1 and MFF). M1 attenuated CS-induced lung histologic damage and mucus hypersecretion in mice, relieved high oxidative stress and reduced the release of IL-6 and IL-8 in BALF. Similarly, it also protected mitochondrial function by regulating the CS-induced imbalance of mitochondrial dynamic proteins. Transcriptome sequencing and Western blotting showed that M1 inhibited CSE- or CS-induced activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) signaling pathway. Conclusion: M1 plays a protective role in inflammation, oxidative stress and mitochondrial dynamics dysfunction caused by CS by inhibiting the PI3K-AKT signaling pathway; thus, it has therapeutic potential for the treatment of CS-induced airway disorders. [ABSTRACT FROM AUTHOR]

Lipoproteins and apolipoproteins are crucial in lipid metabolism, functioning as essential mediators in the transport of cholesterol and triglycerides and being closely related to the pathogenesis of multiple systems, including cardiovascular. Lipoproteins a (Lp(a)), as a unique subclass of lipoproteins, is a low-density lipoprotein(LDL)-like particle with pro-atherosclerotic and pro-inflammatory properties, displaying high heritability. More and more strong evidence points to a possible link between high amounts of Lp(a) and cardiac conditions like atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis (AS), making it a risk factor for heart diseases. In recent years, Lp(a)'s role in other diseases, including neurological disorders and cancer, has been increasingly recognized. Although therapies aimed at low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) have achieved significant success, elevated Lp(a) levels remain a significant clinical management problem. Despite the limited efficacy of current lipid-lowering therapies, major clinical advances in new Lp(a)-lowering therapies have significantly advanced the field. This review, grounded in the pathophysiology of lipoproteins, seeks to summarize the wide-ranging connections between lipoproteins (such as LDL-C and HDL-C) and various diseases, alongside the latest clinical developments, special emphasis is placed on the pivotal role of Lp(a) in cardiovascular disease, while also examining its future potential and mechanisms in other conditions. Furthermore, this review discusses Lp(a)-lowering therapies and highlights significant recent advances in emerging treatments, advocates for further exploration into Lp(a)'s pathogenic mechanisms and its potential as a therapeutic target, proposing new secondary prevention strategies for high-risk individuals. [ABSTRACT FROM AUTHOR]

The outbreaks of severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2 highlight the need for countermeasures to prevent future coronavirus pandemics. Given the unpredictable nature of spillover events, preparing antibodies with broad coronavirus-neutralizing activity is an ideal proactive strategy. Here, we investigated whether SARS-CoV-2 infection and vaccination could provide cross-neutralizing antibodies (nAbs) against zoonotic sarbecoviruses. We evaluated the cross-neutralizing profiles of plasma and monoclonal antibodies constructed from B cells from coronavirus disease 2019 (COVID-19) convalescents and vaccine recipients; against sarbecoviruses originating from bats, civets, and pangolins; and against SARS-CoV-1 and SARS-CoV-2. We found that the majority of individuals with natural infection and vaccination elicited broad nAb responses to most tested sarbecoviruses, particularly to clade 1b viruses, but exhibited very low cross-neutralization to SARS-CoV-1 in both natural infection and vaccination, and vaccination boosters significantly augmented the magnitude and breadth of nAbs to sarbecoviruses. Of the nAbs, several exhibited neutralization activity against multiple sarbecoviruses by targeting the spike receptor-binding domain (RBD) and competing with angiotensin-converting enzyme 2 (ACE2) binding. SCM12-61 demonstrated exceptional potency, with half-maximal inhibitory concentration (IC50) values of 0.001–0.091 μg/mL against tested sarbecoviruses; while VSM9-12 exhibited remarkable cross-neutralizing breadth against sarbecoviruses and SARS-CoV-2 Omicron subvariants, highlighting the potential of these two nAbs in combating sarbecoviruses and SARS-CoV-2 Omicron subvariants. Collectively, our findings suggest that vaccination with an ancestral SARS-CoV-2 vaccine, in combination with broad nAbs against sarbecoviruses, may provide a countermeasure for preventing further sarbecovirus outbreaks in humans. [ABSTRACT FROM AUTHOR]

In recent observational studies, a potential link between prostatitis and prostate cancer (PCa) has been hinted at, yet the causality remains ambiguous. In our endeavor to scrutinize the conceivable causal nexus between prostatitis and PCa, we embarked upon a Mendelian randomization (MR) study. MR circumvents arbitrary groupings by employing genetic variations that have a strong association with the exposure as instrumental variables to infer causal relationships between exposures and outcomes. The etiology of PCa remains elusive. Given that prostatitis and prostate cancer occupy the same anatomical region, MR can more effectively delineate their relationship by mitigating confounding variables. This method can indirectly elucidate disease correlations, thereby contributing to cancer prevention strategies. FinnGen Consortium data were used for the prostatitis genome-wide association study (GWAS), including 74,658 participants. UK biobank baseline data (ncase = 3436, ncontrol = 459574), European Bioinformatics Institute Database (ncase = 79148, ncontrol = 61106), and IEU openGWAS database (ncase = 79148, ncontrol = 61106) were used for PCa outcomes, mostly for European population samples. Data from the GWSAs for prostatitis were compared with data from the three GWASs for PCa, respectively, in an analysis of an MR. Utilizing the inverse variance weighting (IVW) methodology as our primary analytical framework, we delved into a meticulous exploration of the conceivable causal association between prostatitis and PCa. Furthermore, we deployed supplementary methodologies, including Maximum Likelihood, MR-Egger, weighted median, and MR-PRESSO, to thoroughly assess and scrutinize the causality aspect comprehensively. Cochran's Q statistic is employed as a metric to quantify the heterogeneity inherent in instrumental variables. The inverse variance weighted analysis revealed no discernible effect of prostatitis on PCa in the three PCa GWAS databases (odds ratio [OR]: 1.001, 95% Confidence Interval [CI]: 0.999–1.002, p = 0.28), (OR: 1.015, 95% CI: 0.981–1.050, p = 0.40), (OR: 1.015, 95% CI: 0.981–1.050, p = 0.40). Similarly, employing MR-Egger did not yield substantial evidence (OR: 0.999, 95% CI: 0.999–1.002, p = 0.89), (OR: 1.103, 95% CI: 1.006–1.209, p = 0.07), (OR: 1.103, 95% CI: 1.006–1.209, p = 0.07). The weighted median analysis also failed to provide convincing support for the impact of prostatitis on the incidence of PCa (OR: 1.001, 95% CI: 1.000-1.002, p = 0.064), (OR: 0.989, 95% CI: 0.946–1.034, p = 0.64), (OR: 0.989, 95% CI: 0.945–1.036, p = 0.65). The results of the MR showed no causality from prostatitis to PCa. [ABSTRACT FROM AUTHOR]

Parotid glands are one of the most common sites for salivary gland tumors. Conventional imaging techniques have limited usefulness in the quantitative assessment of the parotid glands, making it difficult to differentiate between healthy tissue and tumors, as well as between benign and malignant tumors. Magnetic resonance elastography (MRE) is a non-invasive technique that may potentially overcome these limitations. Nevertheless, due to the size of the parotid gland, increased elastographic resolution is required. This may be achieved by applying shear waves at higher frequencies. However, it also results in stronger attenuation, making the illumination of the parotid challenging. Here, we describe a novel passive driver tailored to the anatomy of the human face, which minimizes the distance shear waves need to travel from the source to the area of interest and thus decreases shear wave attenuation, making high-frequency shear wave MRE feasible. [ABSTRACT FROM AUTHOR]

Older age (≥ 65 years) is associated with impaired responses to influenza vaccination, leading to the preferential recommendation of MF59-adjuvanted (MF59Flu) or high-dose (HDFlu) influenza vaccines for this age group in the United States. Herein, we characterized transcriptomic profiles of CD4+ T cells isolated from 234 recipients (≥ 65 years) of either MF59Flu or HDFlu vaccine, prior to vaccination and 28 days thereafter. We identified 412 and 645 differentially expressed genes (DEGs) in CD4+ T cells of older adults after receiving MF59Flu and HDFlu, respectively. DEGs in CD4+ T cells of MF59Flu recipients were enriched in 14 KEGG pathways, all of which were downregulated. DEGs in CD4+ T cells of HDFlu recipients were enriched in 11 upregulated pathways and 20 downregulated pathways. CD4+ T cells in both vaccine groups shared 50 upregulated genes and 75 downregulated genes, all of which were enriched in 7 KEGG pathways. The remaining 287 and 520 DEGs were specifically associated with MF59Flu and HDFlu, respectively. Unexpectedly, none of these DEGs was significantly correlated with influenza A/H3N2-specific HAI titers, suggesting these DEGs at the individual level may have a limited role in protection against influenza. Our findings emphasize the need for further investigation into other factors influencing immunity against influenza in older adults. [ABSTRACT FROM AUTHOR]

Abnormal subchondral bone remodeling plays a pivotal role in the progression of osteoarthritis (OA). Here, we analyzed subchondral bone samples from OA patients and observed a significant upregulation of ubiquitin carboxy-terminal hydrolase L1 (UCHL1) specifically in subchondral bone osteoclasts. Notably, we found a strong correlation between UCHL1 expression and osteoclast activity in the subchondral bone during OA progression in both human and murine models. Conditional UCHL1 deletion in osteoclast precursors exacerbated OA progression, while its overexpression, mediated by adeno-associated virus 9, alleviated this process in male mice. Mechanistically, RANKL stimulates UCHL1 expression in osteoclast precursors, subsequently stabilizing CD13, augmenting soluble CD13 (sCD13) release, and triggering an autocrine inhibitory effect on the MAPK pathway, thereby suppressing osteoclast formation. These findings unveil a previously unidentified negative feedback loop, RANKL-UCHL1-sCD13, that modulates osteoclast formation and presents a potential therapeutic target for OA. Abnormal subchondral bone remodeling plays a pivotal role in the progression of osteoarthritis. Here, the authors reveal a negative feedback loop, RANKL-UCHL1-sCD13, which limits osteoclastogenesis in the subchondral bone to prevent osteoarthritis progression. [ABSTRACT FROM AUTHOR]

Yoga is effective in binge eating disorder (BED) treatment, but it does not seem effective enough to improve low physical fitness. In contrast, high-intensity interval training (HIIT) is effective in improving physical fitness but has never been studied in the context of BED. In the study, 47 young inactive females with mild to moderate BED were recruited and randomly assigned to a HIIT group (HIIT), a Yoga group (YG), or a control group (CG; age, 19.47 ± 0.74, 19.69 ± 0.874, and 19.44 ± 0.63 years; BMI, 21.07 ± 1.66, 21.95 ± 2.67, and 20.68 ± 2.61 kg/m2, respectively). The intervention groups participated in 8-week specific exercises, while the CG maintained their usual daily activity. Before and after the training, participants were evaluated for BED using the binge eating scale (BES) and for physical fitness. The obtained data were compared within groups and between groups, and a correlation analysis between BES and physical fitness parameters was performed. After the training, the YG presented significant improvements in BES (− 20.25%, p = 0.006, ηp2 = 0.408), fat mass (FM, − 3.13%, p = 0.033, ηp2 = 0.269), and maximal oxygen consumption (VO2max, 11.51%, p = 0.000, ηp2 = 0.601), whereas the HIIT showed significant improvements in body weight (BW, − 1.78%, p = 0.006, ηp2 = 0.433), FM (− 3.94%, p = 0.033, ηp2 = 0.285), and BMI (− 1.80%, p = 0.006, ηp2 = 0.428), but not in BES. Comparisons between groups revealed that both HIIT and YG had significantly higher VO2max levels than CG (HIIT 12.82%, p = 0.006, ηp2 = 0.088; YG: 11.90%, p = 0.009, ηp2 = 0.088) with no difference between HIIT and YG. Additionally, YG presented significantly lower BES than both HIIT (15.45%, p = 0.02, ηp2 = 0.03) and CG (11.91%, p = 0.022, ηp2 = 0.03). In conclusion, Yoga is an effective treatment for BED, but HIIT is not, despite its high efficacy in improving physical fitness. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 21 (FGF21) is essential for modulating hepatic homeostasis, but the impact of FGF21 on liver graft injury remains uncertain. Here, we show that high FGF21 levels in liver graft and serum are associated with improved graft function and survival in liver transplantation (LT) recipients. FGF21 deficiency aggravates early graft injury and activates arachidonic acid metabolism and regional inflammation in male mouse models of hepatic ischemia/reperfusion (I/R) injury and orthotopic LT. Mechanistically, FGF21 deficiency results in abnormal activation of the arachidonate 15-lipoxygenase (ALOX15)/15-hydroxy eicosatetraenoic acid (15-HETE) pathway, which triggers a cascade of innate immunity-dominated pro-inflammatory responses in grafts. Notably, the modulating role of FGF21/ALOX15/15-HETE pathway is more significant in steatotic livers. In contrast, pharmacological administration of recombinant FGF21 effectively protects against hepatic I/R injury. Overall, our study reveals the regulatory mechanism of FGF21 and offers insights into its potential clinical application in early liver graft injury after LT. Marginal liver grafts are associated with a higher risk of graft failure due to their increased susceptibility to ischemia-reperfusion injury. Here, the authors show the regulatory mechanism of fibroblast growth factor 21 and offer insights into its clinical application in early liver graft injury. [ABSTRACT FROM AUTHOR]