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BackgroundResidual astigmatism is common after cataract surgery involving implantation of an intraocular lens, yet the tolerance of presbyopia-correcting intraocular lens to astigmatism of different magnitudes and axes is poorly understood. Here we compared visual acuity and quality in the presence of induced astigmatism after implantation of a trifocal or extended-depth-of-focus (EDOF) intraocular lens, the two widely used presbyopia-correcting intraocular lenses.MethodsAt least 3 months after implantation of a TFNT00 or ZXR00 intraocular lens, patients were analyzed by slit-lamp examination, non-contact tonometry, subjective refraction, iTrace aberrometry, and corneal topography. After correction of residual astigmatism, astigmatism of different magnitudes on different axes was induced using cylindrical lenses, and overall visual acuity was measured, while objective visual quality was measured using the Optical Quality Analysis System II. Subjects were also asked about subjective visual quality using the Visual Function-14 questionnaire.ResultsComparison of 18 individuals who received a trifocal lens and 19 who received an EDOF lens showed that objective visual quality was better in the EDOF group regardless of the magnitude or axis of the induced astigmatism. In both groups, astigmatism of at least −1.00 DC influenced distant vision more severely when the axis was 45° than 0° or 90°, meanwhile astigmatism of at least −1.50 DC influenced near and intermediate vision more severely when the axis was 45° than 0° or 90°.ConclusionTrifocal or EDOF intraocular lenses are less tolerant of oblique astigmatism than astigmatism with or against the rule. EDOF lenses may provide better objective visual quality than trifocal lenses in the presence of astigmatism, regardless of its magnitude or axis.

Background: The predictive value of growth differentiation factor-15 (GDF-15) in coronary microvascular dysfunction (CMD) following primary percutaneous coronary intervention (PPCI) in ST-segment elevation myocardial infarction (STEMI) patients is unclear. Methods: This study continuously recruited STEMI patients treated with PPCI at the Chest Pain Center of Qilu Hospital of Shandong University from April 2023 to December 2023. Blood samples were taken before PPCI and the level of circulating GDF-15 was measured by enzyme-linked immunosorbent assay (ELISA), and the patients were divided into CMD and Control group according to angiographic microvascular resistance (AMR) (cut-off value 2.50 mmHg*s/cm). The differences in GDF-15 expression levels between the two groups were compared, and the predictive value of GDF-15 for CMD was systematically evaluated. Results: A total of 134 patients, with an average age of 59.78 ± 12.69 years and 75.37 % being male, were included in this study. Multivariable logistic regression revealed a significant association between GDF-15 and CMD (adjusted OR = 2.505, 95 % CI: 1.661–3.779, P

Research has identified volatility transmission from the oil market to the tanker freight market through external shocks. However, in the presence of intricate nonlinear structures, the academic literature often encounters difficulties in identifying cycles and their correlations across various timescales. This paper provides a multi-market analysis to comprehend the information from shock effects on different tanker routes and multi-peak fitting. Under different shock regimes, crude oil market and tanker freight rate shocks could transit bi-directly. When events occur, the crude oil market prices the expectations. However, when the actual performance of the future market differs from the traders’ predictions of the future market, a price gap exists. Generally, the trade opportunity is tough to catch up on because only partial information can be found. In this study, we investigate the volatility connection of multi-markets and shock effects to clarify previously undisclosed information using multi-peak analysis. The information gathered and double-checked by cargo markets, crude oil supply-demand balance, and tanker freight prices of various tanker types could assist us in identifying prospective trends and investment opportunities. The volatility of each market, as well as the correlation of multi-markets, gives insights to crude oil dealers, tanker market participants, and energy regulators.

Although the store-operated Ca2+ entry (SOCE) plays a critical role in maintaining Ca2+ homeostasis in vascular endothelial cells (VECs), its role in regulating endothelium-dependent hyperpolarization (EDH)-mediated vasorelaxation is largely unknown. Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are the most common gastrointestinal disorders with no effective cures. The present study applied N,N,N′,N′-tetrakis (2-pyridylmethyl)ethylenediamine (TPEN) as a Ca2+ chelator in the endoplasmic reticulum (ER) to study the SOCE/EDH-mediated vasorelaxation of micro-arteries and their involvements in the pathogenesis of IBD and IBS. Human submucosal arterioles and the second-order branch of 6–8 weeks male C57BL/6 mouse mesenteric arterioles were used, and TPEN-induced vasorelaxation was recorded by Danish DMT520A microvascular measuring system. The mice were fed water with 2.5 % dextran sulfate sodium for 7 days to induce mouse model of ulcerative colitis, and water avoidance stress was used to induce mouse model of IBS. The statistical significance of differences in the means of experimental groups was determined using a t-test for two groups or one-way ANOVA for more than two groups. TPEN concentration-dependently induced vasorelaxation of human colonic submucosal arterioles and the second-order branch of murine mesenteric arteries in endothelium-dependent manner. TPEN-induced vasorelaxation was much greater in the arteries pre-constricted by noradrenaline than those by high K+. While TPEN-induced vasorelaxation was unaffected by inhibitors of NO and PGI2, it was significantly inhibited by the selective inhibitors of IKCa and SKCa channels but was potentiated by their activator. Moreover, TPEN-induced vasorelaxation was attenuated by selective inhibitors of NCX, NKA, SOCE, STIM translocation and Orai transportation. Finally, TPEN-induced vasorelaxation via SOCE/EDH was impaired in colitic mice but remained intact in IBS mice. Interestingly, TPEN could rescue vagus neurotransmitter ACh-induced vasorelaxation that was impaired in IBS mice. Therefore, since TPEN-induced SOCE/EDH-mediated vasorelaxation of mesenteric arteries is well-preserved to be able to rescue ACh-induced vasorelaxation impaired in IBS, TPEN has therapeutic potentials for IBS.

Summary: Positive autoregulation (PAR), one type of network motifs, provides a high phenotypic heterogeneity for cells to better adapt to their microenvironments. Typical mechanosensitive proteins can also form PAR, e.g., integrin mediated PAR, but the role of such mechanical PAR in physiological development and pathological process remains elusive. In this study, we found that transforming growth factor β1 (TGF-β1) and integrin levels decrease with tissue softening after the development of paradentium in vivo in rat model of periodontitis (an inflammatory disease with bone defect). Interestingly, TGF-β1 could induce the formation of mechanical PAR involving the integrin-FAK-YAP axis in mesenchymal stem cells (MSCs) by both in vitro experiments and in silico computational model. The computational model predicted a mechanical PAR involving the bimodal distribution of focus adhesions, which enables cells to accurately perceive extracellular mechanical cues. Thus, our analysis of TGF-β1 mediated mechanosensing mechanism on MSCs may help to better understand the molecular process underlying bone regeneration.

Microplastics (MPs), recognized as an emerging global environmental concern, have been extensively detected worldwide, with specific attention directed towards the Yangtze River Estuary (YRE) and East China Sea (ECS) regions. Despite their critical research significance, there remains a knowledge gap concerning the distribution of MPs in the benthic layer within this area, particularly regarding interactions governing their occurrence. Here we illuminate the distribution of MPs within the benthic layer and unravel the intricate interplay between bottom water and sediment in the YRE and ECS. We find that MPs are notably more abundant in bottom water, ranging from 8 to 175 times higher than in surface water. These MPs predominantly consist of polyester fibers, exhibit a size range between 0.5 and 5.0 mm, and display distinct coloration. Co-occurrence network analysis and Principal Coordinate Analysis confirm a robust correlation between MPs in bottom water and sediment, signifying the pivotal role of bottom water in mediating the distribution and transportation of MPs within the benthic layer. Furthermore, a positive correlation between MPs in sediment and bottom water turbidity underscores the impact of surface sediment resuspension and upwelling on MPs distribution. This study clarifies the intricate interactions within the benthic layer and highlights the crucial role of bottom water as a mediator in the vertical distribution of MPs, advancing our understanding of the “source-to-sink” transport processes governing MPs within water-sediment systems.

Abstract While many studies have sought to explore the degree to which sarcopenia-related traits are associated with cognitive performance, these studies have yielded contradictory results without any clear indication of the causality of such relationships. In efforts to better understand associations between sarcopenia-related traits and cognitive ability, a series of multivariate linear regression assessments were carried out upon datasets derived through the National Health and Nutrition Examination Survey (NHANES). Of these, cognitive performance was assessed by the Digit Symbol Substitution Test (DDST), the Consortium to Establish a Registry for Alzheimer’s Disease Immediate Recall Test (CERAD-IR), Delayed Recall Test (CERAD-DR) and Animal Fluency Test (AFT). Causal relationships between the two were further inferred via a two-sample Mendelian randomization (MR) analysis approach. Sarcopenia-related traits considered in these assessments included walking speed, appendicular skeletal muscle mass (ASM), and hand grip strength (HGS). Walking speed, ASM, and HGS were all significantly independently related to cognitive scores following adjustment for covariates. MR assessments also identified that each 1-SD higher walking speed and appendicular lean mass were causally and respectively associated with a 0.34 [standard error (SE) = 0.09; p

Abstract The rational design of carbon-supported transition-metal single-atom catalysts requires the precise arrangement of heteroatoms within the single-atom catalysts. However, achieving this design is challenging due to the collapse of the structure during the pyrolysis. Here, we introduce a topological heteroatom-transfer strategy to prevent the collapse and accurately control the P coordination in carbon-supported single-atom catalysts. As an illustration, we have prepared self-assembled helical fibers with encapsulated cavities. Within these cavities, adjustable functional groups can chelate metal ions (Nx···Mn+···Oy), facilitating the preservation of the structure during the pyrolysis based phosphidation. This process allows for the transfer of heteroatoms from the assembly into single-atom catalysts, resulting in the precise coordination tailoring. Notably, the Co–P2N2–C catalyst exhibits electrocatalytic performance as a non-noble metal single-atom catalyst for alkaline hydrogen evolution, attaining a current density of 100 mA cm−2 with an overpotential of only 131 mV.

Abstract Background Modifying diet is crucial for diabetes and complication management. Numerous studies have shown that adjusting eating habits to align with the circadian rhythm may positively affect metabolic health. However, eating midpoint, eating duration, and their associations with diabetic kidney disease (DKD) are poorly understood. Methods The National Health and Nutrition Examination Survey (2013–2020) was examined for information on diabetes and dietary habits. From the beginning and ending times of each meal, we calculated the eating midpoint and eating duration. Urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g and/or estimated glomerular filtration rate (eGFR)

Abstract Background Accumulating clinical evidence suggests that lung microbiome is closely linked to the progression of pulmonary diseases; however, it is still controversial which specimen type is preferred for the evaluation of lung microbiome. Methods and results To address this issue, we established a classical acute lung injury (ALI) mice model by intratracheal instillation of lipopolysaccharides (LPS). We found that the bacterial DNA obtained from the bronchoalveolar lavage fluid (BALF), intact lung tissue [Lung(i)], lung tissue after perfused [Lung(p)], and feces of one mouse were enough for 16S rRNA sequencing, except the BALF of mice treated with phosphate buffer saline (PBS), which might be due to the biomass of lung microbiome in the BALF were upregulated in the mice treated with LPS. Although the alpha diversity among the three specimens from lungs had minimal differences, Lung(p) had higher sample-to-sample variation compared with BALF and Lung(i). Consistently, PCoA analysis at phylum level indicated that BALF was similar to Lung(i), but not Lung(p), in the lungs of mice treated with LPS, suggesting that BALF and Lung(i) were suitable for the evaluation of lung microbiome in ALI. Importantly, Actinobacteria and Firmicutes were identified as the mostly changed phyla in the lungs and might be important factors involved in the gut-lung axis in ALI mice. Moreover, Actinobacteria and Proteobacteria might play indicative roles in the severity of lung injury. Conclusion This study shows both Lung(i) and BALF are suitable for the evaluation of murine lung microbiome in ALI, and several bacterial phyla, such as Actinobacteria, may serve as potential biomarkers for the severity of ALI. Video Abstract

Abstract To address issues of high water content and low calorific value during combustion of municipal sludge, we added water-absorbent, easy-to-burn agricultural waste to improve the overall combustion performance. Cotton straw or corn stover were added to the sludge and mixed at high-speed to compare their capacities for improving combustion performance. Scanning Electron Microscopy (SEM) revealed that cotton straw or corn stover attached to the surface of the municipal sludge particles after blending, while analysis of thermogravimetric curves and activation energies of the blends showed that combustion and exhaustion rates increased significantly when 40% cotton straw or corn stover were blended into the sludge. Using the quadrilateral cut-ring boiler as a prototype, the mix of sludge with cotton straw or corn stover was simulated, and FLUENT software was used to obtain the temperature and pollutant emissions of the boiler. Sludge blended with cotton straw or corn stover increased furnace temperature and reduced SO2 and NO emissions, while that with cotton straw burned at higher temperatures with lower SO2 and NO emissions. Overall, the CO content of sludge combustion was lower when blended with proportions of cotton straw or corn stover under 50%. The findings of this study lay a theoretical foundation for treatment of municipal sludge according to local conditions.

Abstract With the rapid growth of Internet of Vehicles (IoV) technology, the performance and privacy of IoV terminals (IoVT) have become increasingly important. This paper proposes a federated learning model for IoVT classification using connection records (FLM-ICR) to address privacy concerns and poor computational performance in analyzing users' private data in IoV. FLM-ICR, in the horizontally federated learning client-server architecture, utilizes an improved multi-layer perceptron and logistic regression network as the model backbone, employs the federated momentum gradient algorithm as the local model training optimizer, and uses the federated Gaussian differential privacy algorithm to protect the security of the computation process. The experiment evaluates the model's classification performance using the confusion matrix, explores the impact of client collaboration on model performance, demonstrates the model's suitability for imbalanced data distribution, and confirms the effectiveness of federated learning for model training. FLM-ICR achieves the accuracy, precision, recall, specificity, and F1 score of 0.795, 0.735, 0.835, 0.75, and 0.782, respectively, outperforming existing research methods and balancing classification performance and privacy security, making it suitable for IoV computation and analysis of private data.

As an important spice species in Rutaceae, the Sichuan pepper (Zanthoxylum armatum) can provide pungent and numbing taste, as well as aroma in its mature fruit. Here we assembled a chromosome-level genome of green prickly ash which was widely cultivated in a major production area including Chongqing and Sichuan province, China. We generated 712 Gb (∼112 × ) PacBio long reads and 511 Gb (∼82 × ) Hi-C data, and yielded an assembly of 99 pseudochromosomes with total size of 5.32 Gb and contig N50 of 796 kb. The genomic analyses and cytogenetic experiments both indicated that the cultivar ‘Zhuye Huajiao’ was a triploid. We identified a Zanthoxylum-specific whole genome duplication event emerging about 24.8 million years ago (Mya). We also detected a transposition burst event (0.3–0.4 Mya) responsible for the large genome size of Z. armatum. Metabolomic analysis of the Zanthoxylum fruits during development stages revealed profiles of 39 volatile aroma compounds and 528 secondary metabolites, from which six types of sanshools were identified. Based on metabolomic and transcriptomic network analysis, we screened candidate genes encoding long chain acyl-CoA synthetase, fatty acid desaturase, branched-chain amino acid aminotransferase involved in sanshool biosynthesis and three genes encoding terpene synthase during fruit development. The multi-omics data provide insights into the evolution of Zanthoxylum and molecular basis of numbing and aroma flavor of Sichuan pepper.

Metabolic modeling and machine learning (ML) are crucial components of the evolving next-generation tools in systems and synthetic biology, aiming to unravel the intricate relationship between genotype, phenotype, and the environment. Nonetheless, the comprehensive exploration of integrating these two frameworks, and fully harnessing the potential of fluxomic data, remains an unexplored territory. In this study, we present, rigorously evaluate, and compare ML-based techniques for data integration. The hybrid model revealed that the overexpression of six target genes and the knockout of seven target genes contribute to enhanced ethanol production. Specifically, we investigated the influence of succinate dehydrogenase (SDH) on ethanol biosynthesis in Saccharomyces cerevisiae through shake flask experiments. The findings indicate a noticeable increase in ethanol yield, ranging from 6 % to 10 %, in SDH subunit gene knockout strains compared to the wild-type strain. Moreover, in pursuit of a high-yielding strain for ethanol production, dual-gene deletion experiments were conducted targeting glycerol-3-phosphate dehydrogenase (GPD) and SDH. The results unequivocally demonstrate significant enhancements in ethanol production for the engineered strains Δsdh4Δgpd1, Δsdh5Δgpd1, Δsdh6Δgpd1, Δsdh4Δgpd2, Δsdh5Δgpd2, and Δsdh6Δgpd2, with improvements of 21.6 %, 27.9 %, and 22.7 %, respectively. Overall, the results highlighted that integrating mechanistic flux features substantially improves the prediction of gene knockout strains not accounted for in metabolic reconstructions. In addition, the finding in this study delivers valuable tools for comprehending and manipulating intricate phenotypes, thereby enhancing prediction accuracy and facilitating deeper insights into mechanistic aspects within the field of synthetic biology.

Abstract Background Whether distributions and prognostic values of high-sensitivity cardiac troponin (hs-cTn) T and I are different across normoglycemic, prediabetic, and diabetic populations is unknown. Methods 10127 adult participants from the National Health and Nutrition Examination Survey 1999–2004 with determined glycemic status and measurement of at least one of hs-cTn assays were included, from whom healthy participants and presumably healthy diabetic and prediabetic participants were selected to investigate pure impacts of glycemic status on distributions of hs-cTn. The nonparametric method and bootstrapping were used to derive the 99th upper reference limits of hs-cTn and 95% CI. Participants with available follow-up and hs-cTn concentrations of all 4 assays were included in prognostic analyses. Associations of hs-cTn with all-cause and cardiac-specific mortality were modeled by Cox proportional hazard regression under the complex survey design. The incremental value of hs-cTn to an established risk score in predicting cardiac-specific mortality was assessed by the 10-year area under time-dependent receiver operating characteristic curve (AUC) using the Fine-Grey competing risk model. Results Among 9714 participants included in prognostic analyses, 5946 (61.2%) were normoglycemic, 2172 (22.4%) prediabetic, and 1596 (16.4%) diabetic. Hyperglycemic populations were older than the normoglycemic population but sex and race/ethnicity were similar. During the median follow-up of 16.8 years, hs-cTnT and hs-cTnI were independently associated with all-cause and cardiac-specific mortality across glycemic status. In the diabetic population, adjusted hazard ratios per 1-standard deviation increase of log-transformed hs-cTnT and hs-cTnI (Abbott) concentrations were 1.77 (95% CI 1.48–2.12; P

Abstract Background Hematological metastasis has been recognized as a crucial factor contributing to the high rates of metastasis and mortality observed in colorectal cancer (CRC). Notably, exosomes derived from cancer cells participate in the formation of CRC pre-metastatic niches; however, the mechanisms underlying their effects are largely unknown. While our preliminary research revealed the role of exosome-derived disintegrin and metalloproteinase 17 (ADAM17) in the early stages of CRC metastasis, the role of exosomal ADAM17 in CRC hematogenous metastasis remains unclear. Methods In the present study, we isolated and purified exosomes using ultracentrifugation and identified exosomal proteins through quantitative mass spectrometry. In vitro, co-culture assays were conducted to evaluate the impact of exosomal ADAM17 on the permeability of the blood vessel endothelium. Vascular endothelial cell resistance, the cell index, membrane protein separation, flow cytometry, and immunofluorescence were employed to investigate the mechanisms underlying exosomal ADAM17-induced vascular permeability. Additionally, a mouse model was established to elucidate the role of exosomal ADAM17 in the modulation of blood vessel permeability and pre-metastatic niche formation in vivo. Results Our clinical data indicated that ADAM17 derived from the circulating exosomes of patients with CRC could serve as a blood-based biomarker for predicting metastasis. The CRC-derived exosomal ADAM17 targeted vascular endothelial cells, thus enhancing vascular permeability by influencing vascular endothelial cadherin cell membrane localization. Moreover, exosomal ADAM17 mediated the formation of a pre-metastatic niche in nude mice by inducing vascular leakage, thereby promoting CRC metastasis. Nonetheless, ADAM17 selective inhibitors effectively reduced CRC metastasis in vivo. Conclusions Our results suggest that exosomal ADAM17 plays a pivotal role in the hematogenous metastasis of CRC. Thus, this protein may serve as a valuable blood-based biomarker and potential drug target for CRC metastasis intervention.

Abstract. Background:. Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer associated with poor prognosis and limited treatment options. The androgen receptor (AR) has emerged as a potential therapeutic target for luminal androgen receptor (LAR) TNBC. However, multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits. This study aimed to investigate the role of AR in TNBC and its detailed mechanism. Methods:. Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4 (NECTIN4) expression in TNBC tissues. Then, in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta (ERβ) in TNBC. Chromatin immunoprecipitation sequencing (ChIP-seq), co-immunoprecipitation (co-IP), molecular docking method, and luciferase reporter assay were performed to identify key molecules that affect the function of AR. Results:. Based on the TNBC tissue array analysis, we revealed that ERβ and AR were positive in 21.92% (32/146) and 24.66% (36/146) of 146 TNBC samples, respectively, and about 13.70% (20/146) of TNBC patients were ERβ positive and AR positive. We further demonstrated the pro-tumoral effects of AR on TNBC cells, however, the oncogenic biology was significantly suppressed when ERβ transfection in LAR TNBC cell lines but not in AR-negative TNBC. Mechanistically, we identified that NECTIN4 promoter –42 bp to –28 bp was an AR response element, and that ERβ interacted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial–mesenchymal transition in tumor progression. Conclusions:. This study suggests that ERβ functions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation. Therefore, our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.

In China's Tianwen-2 mission, a dual-frequency radar will be carried out to detect the asteroid 2016 HO3. The dual-frequency radar can acquire the information of the asteroid's surface and internal structure. There are few studies about the radar detection of the asteroid 2016 HO3 and it is unclear what information can be acquired from the radar images. In this article, the radar images of the asteroid under nadir and oblique observations are simulated with the two-scale model of the Kirchhoff approximation/small-perturbation method. The radar images at 900 and 150 MHz are simulated to study the backscattering from the asteroid's surface and the detectability of the internal structure in the asteroid. The influences of the asteroid characteristics, such as the shape, surface roughness, internally embedded object, and the loss tangent of the media, on the radar images and the detectability of internal structure are discussed under nadir and oblique observations. The simulations provide a reference for future data analysis in the Tianwen-2 mission.

Hematopoietic stem cell transplantation (HSCT) is a crucial treatment option for hematological disorders. This study aims to design and develop a blockchain-based system tailored explicitly for HSCT typing and evaluate its performance and capabilities. The system, built on Hyperledger Fabric 2.4.6 and integrated with LevelDB and MySQL databases, implements features such as data on-chaining, access control, information retrieval, and matching through chaincode. It ensures accurate and efficient human leukocyte antigen (HLA) typing while protecting patient and hospital data security. Tests demonstrate the system’s ability to safeguard data security and reliability effectively. Performance metrics, including block size, CPU utilization, network throughput, and response latency, were evaluated on Ubuntu 20.04.2 operating systems using VMware Workstation 16 Pro and Docker containerization. By leveraging blockchain’s traceability and immutability, the system achieves data security, reliability, and verifiability, enabling faster and more accurate typing and improved healthcare efficiency. This innovative approach optimizes user experience, maintains data integrity, and ensures privacy. Future integration with existing databases could enable secure data sharing among healthcare institutions, allowing rapid verification of data ownership and unified authentication. This study contributes a significant advancement in hematologic disease treatment and research, offering practical implications for improving HSCT processes.

Abstract This study aims to investigate the feasibility and efficacy of anterior atlantoaxial motion preservation fixation (AMPF) in treating axis complex fractures involving the odontoid process fracture and Hangman’s fractures with C2/3 instability. A retrospective study was conducted on eight patients who underwent AMPF for axis complex fractures at the General Hospital of Central Theater Command from February 2004 to October 2021. The types of axis injuries, reasons for injuries, surgery time, intraoperative blood loss, spinal cord injury classification (American Spinal Injury Association, ASIA), as well as complications and technical notes, were documented. This study included eight cases of type II Hangman’s fracture, five cases of type II and three cases of type III odontoid process fracture. Five patients experienced traffic accidents, while three patients experienced falling injuries. All patients underwent AMPF surgery with an average intraoperative blood loss of 288.75 mL and a duration of 174.5 min. Two patients experienced dysphagia 1 month after surgery. The patients were followed up for an average of 15.63 months. One case improved from C to E in terms of neurological condition, three cases improved from D to E, and four cases remained at E. Bony fusion and Atlantoaxial Motion Preservation were successfully achieved for all eight patients. AMPF is a feasible and effective way for simultaneous odontoid process fracture and Hangman’s fractures with C2/3 instability, while preserving atlantoaxial movement.

Abstract Diabetic nephropathy (DN), a common microvascular complicating disease of diabetes. Lupenone, a pentacyclic triterpenoid, has anti-inflammatory effects and can prevent type 2 diabetes mellitus and treat renal damage, however, the effects and mechanisms of lupenone in DN remain unclear. Thereby,the MTT method was used to investigate the antiproliferative effect of lupenoneon the cell line rat glomerular mesangial cells (HBZY-1). Molecular docking was used to investigate the combination of lupenone and MCP-1, IL-1β, TNF-α, IKKβ, IκBα, and NF-κB p65 proteins. The expression of mRNA of the pro-inflammatory cytokines (MCP-1, IL-1β and TNF-α) and the NF-κB signalling pathway in HBZY-1 cells were assessed by RT-PCR. The protein expressions of pro-inflammatory cytokines and NF-κB pathway were got by Western blot. Result showed that lupenone inhibited the proliferative activity of HBZY-1 cells at non-cytotoxic concentrations. Molecular docking results showed that lupenone combined well with the target proteins. Moreover, lupenone could significantly reduced the mRNA and protein expressions for pro-inflammatory cytokines and IKKβ, p-p65 and p-IκBα. Lupenone may play an anti-inflammatory role in DN treatment by inhibiting the NF-κB signalling pathway. These results provided a new understanding of the pharmacological mechanisms of lupenone in treatment of DN.

Two broadband dual-polarized band-notched crossed dipole antennas based on the grounded coplanar waveguide (GCPW) filter for 2G/3G/4G/5G base station are proposed in this paper. Two antennas with two and three radiation nulls are displayed to demonstrate the design innovation. Firstly, a wideband crossed dipole antenna with GCPW feed structure is designed, and its coverage frequency is 1.7-3.6 GHz. Then, a compact GCPW second-order hybrid bandstop filter is designed using defected ground structure (DGS) and defected microstrip structure (DMS). The DGS-DMS filter are embedded inside the antenna radiator to achieve the stopband covering 2.9-3.1 GHz with only one dielectric substrate. At last, a miniaturized GCPW third-order DGS-DMS highly selective bandstop filter is integrated in wideband antenna to realize the stopband of 2.87-3.17 GHz. The proposed band-notched antenna uses only one substrate. Compared with the antenna using second-order filter, the antenna using third-order filter has one more radiation null, wider stopband of 2.87-3.17 GHz and higher selectivity.

Abstract The future state of drought in China under climate change remains uncertain. This study investigates drought events, focusing on the region of China, using simulations from five global climate models (GCMs) under three Shared Socioeconomic Pathways (SSP1-2.6, SSP3-7.0, and SSP5-8.5) participating in the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP3b). The daily Standardized Precipitation Evapotranspiration Index (SPEI) is employed to analyze drought severity, duration, and frequency over three future periods. Evaluation of the GCMs’ simulations against observational data indicates their effectiveness in capturing historical climatic change across China. The rapid increase in CO2 concentration under high-emission scenarios in the mid- and late-future century (2040–2070 and 2071–2100) substantially influences vegetation behavior via regulation on leaf stomata and canopy structure. This regulation decelerates the increase in potential evapotranspiration, thereby mitigating the sharp rise in future drought occurrences in China. These findings offer valuable insights for policymakers and stakeholders to develop strategies and measures for mitigating and adapting to future drought conditions in China.

Abstract We propose a low-loss compound structure consisting of a multiplexed rectangular dielectric grating and a waveguide layer, which can function as multi-band optical filters and sensors in TE and TM polarization by utilizing the resonant mode of the waveguide (WG) and the hybrid SP, respectively. By manipulating the parameters and subsequently constraining the local density of multi-resonant modes to several distinct resonant wavelengths, we propose a novel category of highly sensitive refractive index sensing platforms. Spectral shifts ranging from 110 to 131 nm/RIU with FOM of (22, 26.2)/RIU under TE polarization and 80 to 114 nm/RIU with FOM of (5.7, 8.1)/RIU under TM polarization can be accurately discerned for multiple individual analytes across a broad spectral range. The proposed structures offer enhanced flexibility in the design of structures across a wide spectral range, catering to various potential applications in multi-band optical filters, sensors, and photodetectors.

Magnetic metals have attracted extensive attention in microwave absorption for comprehensive merits of high magnetic loss and suitability for mass productions. Nevertheless, the applications have been limited by shortcomings of high conductivity and inadequate impedance matching. In this study, we have successfully synthesized a biphasic magnetic Sm2O3@Co composite through a facile one-step precipitation method. The resultant features a well-designed structure with spherical cores and flaky shells, exhibiting highly-tunable absorption performance over 2–18 GHz. Particularly, under 20 wt% filling ratio with paraffin, the Sm2O3@Co composite achieved minimum reflection loss (RLmin) of −30.1 dB and effective absorbing bandwidth (EAB) of 6.22 GHz at only 1.7 mm. The dielectric and magnetic losses could be easily modulated by simply changing the induced Co ratios. Through a systematic study, the microwave absorption mechanisms of the Sm2O3@Co magnetic composite have been comprehensively elucidated. This research offers a fresh perspective on developing highly efficient electromagnetic wave absorbents based on traditional magnetic metals.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disease characterized by irreversible scarring of the lung parenchyma. Despite various interventions aimed at mitigating several different molecular aspects of the disease, only two drugs with limited clinical efficacy have so far been approved for IPF therapy. Objective We investigated the therapeutic efficacy of amifostine, a detoxifying drug clinically used for radiation-caused cytotoxicity, in bleomycin-induced murine pulmonary fibrosis. Methods C57BL6/J mice were intratracheally instilled with 3 U/kg of bleomycin. Three doses of amifostine (WR-2721, 200 mg/kg) were administered intraperitoneally on days 1, 3, and 5 after the bleomycin challenge. Bronchoalveolar lavage fluid (BALF) was collected on day 7 and day 21 for the assessment of lung inflammation, metabolites, and fibrotic injury. Human fibroblasts were treated in vitro with transforming growth factor beta 1 (TGF-β1), followed by amifostine (WR-1065, 1–4 µg/mL) treatment. The effects of TGF-β1 and amifostine on the mitochondrial production of reactive oxygen species (ROS) were assessed by live cell imaging of MitoSOX. Cellular metabolism was assessed by the extracellular acidification rate (ECAR), the oxygen consumption rate (OCR), and the concentrations of various energy-related metabolites as measured by mass spectrum (MS). Western blot analysis was performed to investigate the effect of amifostine on sirtuin 1 (SIRT1) and adenosine monophosphate activated kinase (AMPK). Results Three doses of amifostine significantly attenuated lung inflammation and pulmonary fibrosis. Pretreatment and post-treatment of human fibroblast cells with amifostine blocked TGF-β1-induced mitochondrial ROS production and mitochondrial dysfunction in human fibroblast cells. Further, treatment of fibroblasts with TGF-β1 shifted energy metabolism away from mitochondrial oxidative phosphorylation (OXPHOS) and towards glycolysis, as observed by an altered metabolite profile including a decreased ratio of NAD + /NADH and increased lactate concentration. Treatment with amifostine significantly restored energy metabolism and activated SIRT1, which in turn activated AMPK. The activation of AMPK was required to mediate the effects of amifostine on mitochondrial homeostasis and pulmonary fibrosis. This study provides evidence that repurposing of the clinically used drug amifostine may have therapeutic applications for IPF treatment. Conclusion Amifostine inhibits bleomycin-induced pulmonary fibrosis by restoring mitochondrial function and cellular metabolism.

Abstract Background Accompanying islet α- and β-cell dysregulation in type 2 diabetes (T2D) at the microscopic scale, alterations in body composition at the macroscopic scale may affect the pathogenesis of T2D. However, the connections between body composition and islet α-cell and β-cell functions in T2D have not been thoroughly explored. Methods For this cross-sectional study, we recruited a total of 729 Chinese Han patients with T2D in a consecutive manner. Dual-energy X-ray absorptiometry (DXA) was used to measure body composition, which included total bone-free mass, total fat and lean mass, trunk fat and lean mass and limb fat and lean mass. Every patient underwent an oral glucose tolerance test to simultaneously detect glucose, C-peptide and glucagon. The indices of islet α-cell function included fasting glucagon levels and the area under the curve of glucagon after a challenge (AUCglucagon), while the indices of β-cell function included the insulin sensitivity index derived from C-peptide (ISIC-peptide) and the area under the curve of C-peptide after a challenge (AUCC-peptide). Results Among all patients, fat mass, especially trunk fat mass, was significantly correlated with ISIC-peptide and AUCC-peptide levels (r = − 0.330 and 0.317, respectively, p

Accurate paddy rice mapping is crucial for ensuring food security and guiding agricultural production. Vegetation indices are extensively employed to map paddy rice. However, most traditional normalized indices tend to be oversaturated during periods of lush vegetation due to normalization errors, resulting in uncertainties in paddy rice mapping. To address this issue, we introduce a novel red-edge rice index (RERI) in this study; this index comprises information from red, near-infrared, and red-edge bands without normalization. To extract single- and double-cropping rice features from potential rice areas, we employ GF-6 and Sentinel-2 images based on the proposed RERI and the random forest algorithm. The proposed method is validated in the Dingcheng District of Changde city, China, and the results are compared with those based on three normalized vegetation indices. The results show that the RERI yielded the highest levels of the accuracy for all the metrics, achieving an overall accuracy (OA) of 92.50% and a kappa coefficient of 0.8875. The RERI exhibited F1 scores of 92.26% for single-cropping rice, 93.00% for double-cropping rice, and 92.28% for non-rice areas. Our results highlight the potential of using the RERI for rice identification, and the effectiveness of our method for rice extraction is demonstrated.

Patients with advanced hepatocellular carcinoma (HCC) are not sensitive to sorafenib (SOR), therefore, combination therapy is required. In this study, an improved thin-film dispersion and post-insertion anchoring technique was utilized to construct a dual-targeted co-delivery SOR and docetaxel (DTX) liposome drug delivery system, folate/chondroitin sulfate with SOR/DTX-modified liposomes (FA/CS@SDLP), to jointly enhance the anti-recurrence and metastasis of HCC. FA/CS@SDLP can establish the gradual release of the two drugs because of successful lysosomal escape in the condensed hyaluronidase environment. The results indicated that modification with folate (FA) and chondroitin sulfate (CS) significantly enhanced the cellular uptake of FA/CS@SDLP and the internalization of SOR/DTX in HepG2 cells through FA and CD44 receptor-mediated endocytosis. Compared to free drugs or the mono-targeted liposomal system (FA@SDLP), FA/CS@SDLP presented higher potency against HepG2 cells regarding pro-apoptosis, anti-proliferation, and anti-metastasis (migration and invasion). Moreover, a more satisfactory antitumor efficacy was observed for FA/CS@SDLP in the pulmonary metastasis of HCC in a mouse model. In summary, dual-targeted co-delivery of liposomes can synergistically treat HCC recurrence and metastasis, providing a new approach for the clinically accurate treatment of HCC.

Background Patients with idiopathic membranous nephropathy (IMN) are more likely to be complicated by venous thromboembolism (VTE). The aim of the study was to investigate the potential association between anti-phospholipase A2 receptor (PLA2R) antibodies and hypercoagulability in patients with IMN.Methods A total of 168 patients with biopsy-proven IMN and 36 patients with biopsy-proven minimal change disease (MCD) were enrolled in this study. The clinical data, serum anti-PLA2R antibodies and coagulation-related indices of the patients were retrospectively analyzed.Results Patients with IMN were categorized into glomerular PLA2R staining-positive (GAg+) IMN group and glomerular PLA2R staining-negative (GAg-) IMN group in the study. Patients with IMN who were GAg + had lower PT, APTT and R time than patients with IMN who were GAg-, while the CI value was higher in patients with IMN who were GAg+. Patients with IMN who were GAg + were divided into the SAb+/GAg + group and the SAb-/GAg + group. Patients with IMN who were SAb+/GAg + had higher Fib and MA values than patients with IMN who were SAb-/GAg+. Correlation analysis showed that serum anti-PLA2R antibodies were positively correlated with fibrinogen, D-dimer, K time, CI value, α-angle, and MA value. Multiple linear regression analysis indicated that anti-PLA2R antibodies were independently correlated with fibrinogen and MA value.Conclusion Our study provides a new perspective on the underlying mechanisms of hypercoagulability in patients with IMN. Anti-PLA2R antibodies are associated with hypercoagulability in patients with IMN and may affect coagulation in patients with IMN by affecting platelet aggregation function and fibrinogen counts.

Objectives To investigate the long-term efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for multiple uterine fibroids and the factors associated with recurrence.Materials and methods Five hundred and forty-nine patients with multiple uterine fibroids treated with USgHIFU from June 2017 to June 2019 were retrospectively analyzed. The Pictorial Blood Loss Assessment Chart (PBAC) was used to assess menstrual blood loss. The patients were asked to undergo pre- and post-USgHIFU magnetic resonance imaging (MRI) and complete routine follow-up after USgHIFU. Cox regression analysis was used to investigate the risk factors associated with recurrence.Results The median number of fibroids per patient was 3 (interquartile range: 3–4), and a total of 1371 fibroids were treated. Among them, 446 patients completed 3 years follow-up. Recurrence, defined as PBAC score above or equal to 100 and/or the residual fibroid volume increased by 10%, was detected in 90 patients within 3 years after USgHIFU, with a cumulative recurrence rate of 20.2% (90/446). The multi-factor Cox analysis showed that age was a protective factor for recurrence. Younger patients have a greater chance of recurrence than older patients. Mixed hyperintensity of fibroids on T2WI and treatment intensity were risk factors for recurrence. Patients with hyperintense uterine fibroids and treated with lower treatment intensity were more likely to experience recurrence than other patients after USgHIFU. No major adverse effects occurred.Conclusions USgHIFU can be used to treat multiple uterine fibroids safely and effectively. The age, T2WI signal intensity and treatment intensity are factors related to recurrence.

Septic shock is a life-threatening disease worldwide often associated with thrombocytopenia. Platelets play a crucial role in bridging the gap between immunity, coagulation, and endothelial cell activation, potentially influencing the course of the disease. However, there are few studies specifically evaluating the impact of thrombocytopenia on the prognosis of pediatric patients. Therefore, the study investigates effects of early thrombocytopenia in the prognosis of children with septic shock. Pediatric patients with septic shock from 2015 to 2022 were included monocentrically. Thrombocytopenia was defined as a platelet count of

Background The analytical renal pathology system (ARPS) based on convolutional neural networks has been used successfully in native IgA nephropathy (IgAN) patients. Considering the similarity of pathologic features, we aim to evaluate the performance of the ARPS in allograft IgAN patients and broaden its implementation.Methods Biopsy-proven allograft IgAN patients from two different centers were enrolled for internal and external validation. We implemented the ARPS to identify glomerular lesions and intrinsic glomerular cells, and then evaluated its performance. Consistency between the ARPS and pathologists was assessed using intraclass correlation coefficients. The association of digital pathological features with clinical and pathological data was measured. Kaplan-Meier survival curve and cox proportional hazards model were applied to investigate prognosis prediction.Results A total of 56 biopsy-proven allograft IgAN patients from the internal center and 17 biopsy-proven allograft IgAN patients from the external center were enrolled in this study. The ARPS was successfully applied to identify the glomerular lesions (F1-score, 0.696–0.959) and quantify intrinsic glomerular cells (F1-score, 0.888–0.968) in allograft IgAN patients rapidly and precisely. Furthermore, the mesangial hypercellularity score was positively correlated with all mesangial metrics provided by ARPS [Spearman’s correlation coefficient (r), 0.439–0.472, and all p values < 0.001]. Besides, a higher allograft survival was noticed among patients in the high-level groups of the maximum and ratio of endothelial cells, as well as the maximum and density of podocytes.Conclusion We propose that the ARPS could be implemented in future clinical practice with outstanding capability.

Cynoglossus semilaevis (half-smooth tongue sole) is an important aquaculture species that has a ZW/ZZ sex-determination system (females, ZW; males, ZZ). Some genotypic females may develop phenotypic males, and are known as pseudomales (ZW). These pseudomales can develop mature testes and produce sperm. However, previous studies have shown that pseudomales cannot produce sperms bearing W chromosome (W sperm). In this study, transcriptomic, proteomic, and ubiquitinated proteomic analyses were employed simultaneously to investigate the differences in gonads between pseudomales and normal males. Functional enrichment analysis of the differentially expressed genes/proteins showed that non-coding RNA metabolic processes and RNA degradation were more active in the gonads of pseudomales, and they showed higher levels of ubiquitination compared to males. In addition, most genes/proteins related to sperm morphogenesis expressed downwards in pseudomales. These genes included genes located exclusively on the Z chromosome, such as sperm flagellar protein 2 (spef2), doublesex and mab-3 related transcription factor 1 (dmrt1), doublesex and mab-3 related transcription factor 3 (dmrt3), and cilia- and flagella-associated protein 157 (cfap157). These findings characterized the transcriptional and proteomic profiles of the gonads of pseudomales and males, and suggested that W sperm were absent in pseudomales, possibly due to the disruption of sperm morphogenesis, resulting from W chromosome lacking spermatogenesis-related genes.

Abstract 4‐Coumarate‐CoA ligase (4CL) gene plays vital roles in plant growth and development, especially the regulation of lignin metabolism and flavonoid synthesis. To investigate the potential function of 4CL in the lignin biosynthesis of Ginkgo biloba, this study identified two 4CL genes, Gb4CL1 and Gb4CL2, from G. biloba genome. Based on the phylogenetic tree analysis, Gb4CL1 and Gb4CL2 protein were classified into Class I, which has been confirmed to be involved in lignin biosynthesis. Therefore, it can be inferred that these two genes may also participate in lignin metabolism. The tissue‐specific expression patterns of these two genes revealed that Gb4CL1 was highly expressed in microstrobilus, whereas Gb4CL2 was abundant in immature leaves. The onion transient expression assay indicated that Gb4CL1 was predominantly localized in the nucleus, indicating its potential involvement in nuclear functions, while Gb4CL2 was observed in the cell wall, suggesting its role in cell wall‐related processes. Phytohormone response analysis revealed that the expression of both genes was upregulated in response to indole acetic acid, while methyl jasmonate suppressed it, gibberellin exhibited opposite effects on these genes. Furthermore, Gb4CL1 and Gb4CL2 expressed in all tissues containing lignin that showed a positive correlation with lignin content. Thus, these findings suggest that Gb4CL1 and Gb4CL2 are likely involved in lignin biosynthesis. Gb4CL1 and Gb4CL2 target proteins were successfully induced in Escherichia coli BL21 with molecular weights of 85.5 and 89.2 kDa, proving the integrity of target proteins. Our findings provided a basis for revealing that Gb4CL participated in lignin synthesis in G. biloba.

Abstract Background Systemic immune‐inflammation index (SII) provides convincing evaluation of systemic immune and inflammatory condition in human body. Its correlation with prostate cancer (PCa) risk remains uncharted. The principal objective of this investigation was to elucidate the association between SII and the risk for PCa in middle‐aged and elderly males. Materials and Methods Analysis entailed multivariate linear and logistic regression, generalized additive model, and smoothing curve fitting using resource from 2007 to 2010 National Health and Nutrition Examination Survey (NHANES). To ascertain robustness and consistency of this association across different demographic strata, we conducted rigorous subgroup analyses and interaction tests. Results Among 3359 participants, those with elevated SII displayed higher total prostate‐specific antigen (tPSA) levels, higher risk for PCa, and lower free/total PSA (f/t PSA) ratio. Specifically, each unit increase of log2 (SII) was associated with a 0.22 ng/mL increase in tPSA (β: 0.22, 95% confidence intervals [CI] 0.05–0.38), a 2.22% decline in f/t PSA ratio (β: −2.22, 95% CI −3.20 to −1.23), and a 52% increased odds of being at high risk for PCa (odds ratio [OR]: 1.52, 95% CI 1.13–2.04). People in the top quartile of log2 (SII) exhibited 0.55 ng/mL increased tPSA (β: 0.55, 95% CI 0.19–0.90), 4.39% reduced f/t PSA ratio (β: −4.39, 95% CI −6.50 to −2.27), and 168% increased odds of being at high risk for PCa (OR: 2.68, 95% CI 1.32–5.46) compared to those in the bottom quartile. Conclusion Systemic immune and inflammatory condition, as represented by SII, is independently and positively associated with tPSA levels and the risk for PCa, as well as independently and negatively associated with f/t PSA ratio among middle‐aged and older US males. These findings may enhance the effectiveness of PCa screening in predicting positive biopsy results.

Objective Systemic lupus erythematosus (SLE) is a type of autoimmune disease that involves multiple organs involved as well as cytokine dysregulation. The treatment of SLE is still challenging due to the side effects of the different drugs used. Receptor-interacting protein kinase 1 (RIPK1) is a kinase involved in T cell homeostasis and autoinflammation. Although clinical trials have shown that RIPK1 inhibition exhibits significant efficacy in different autoimmune diseases, its role in SLE remains unclear.Methods MRL/lpr lupus-prone mice received RIPK1 inhibitor ZJU37 or vehicle intraperitoneally for 10 weeks. A BM12-induced chronic graft-versus-host-disease (cGVHD) lupus-like model was introduced in RIPK1 D138N mice or C57BL/6 mice. Nephritis, serum autoantibody levels, dysregulation of adaptive immune response and cytokines were compared in treated and untreated mice.Results ZJU37 alleviated the clinical features of the MRL/lpr mice including nephritis and anti-dsDNA antibody production. In addition, ZJU37 treatment reduced the proportion of double-negative T cells in the spleen and the cytokines of TNFα, IFN-γ, IL-6, IL-17 and IL-1β in the serum. Moreover, RIPK1 D138N mice were able to prevent the cGVHD lupus-like model from SLE attack, manifesting as anti-dsDNA antibody production, the proliferation of germinal centre B cells, plasma cells, and T follicular helper cells as well as IgG and C3 deposits in kidneys.Conclusion RIPK1 inhibition has a protective effect in the mouse model of SLE and can potentially become a new therapeutic target for SLE in humans.

IntroductionThe online study investigated the sleep, psychological conditions, and risk factors during the wave of transmission of COVID-19 since December 7, 2022.MethodsWe distributed questionnaires through networking mediums to residents to gather information about COVID-19 infection, sleep, and mental status.ResultsDuring the extraordinary period in China, 91.9% of 1094 participants claimed to be infected with COVID-19, 36.8% reported poor sleep quality, 75.9% reported anxiety, and 65.5% reported depression. In retrospect, people have experienced lower sleep quality, longer sleep latency, enhanced rising time, and decreased sleep efficiency after the infection wave. After adjusting confounding factors, the elderly, women, urban residents, people with comorbidity, anxiety, depression, stress state, and COVID-19 infection have high risks for sleep disorders during the period.DiscussionThe survey indicates that sleep disturbance caused by COVID-19 involves multiple dimensions, such as physiology, psychology, and society. The COVID-19 infection-related sleep problem should be taken seriously. Apart from conventional treatment, psychological issues of insomnia can not be ignored.

Abstract Despite accumulating evidence linking defective lysosome function with autoimmune diseases, how the catabolic machinery is regulated to maintain immune homeostasis remains unknown. Late endosomal/lysosomal adaptor, MAPK and mTOR activator 5 (Lamtor5) is a subunit of the Ragulator mediating mechanistic target of rapamycin complex 1 (mTORC1) activation in response to amino acids, but its action mode and physiological role are still unclear. Here it is demonstrated that Lamtor5 level is markedly decreased in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE). In parallel, the mice with myeloid Lamtor5 ablation developed SLE‐like manifestation. Impaired lysosomal function and aberrant activation of mTORC1 are evidenced in Lamtor5 deficient macrophages and PBMCs of SLE patients, accompanied by blunted autolysosomal pathway and undesirable inflammatory responses. Mechanistically, it is shown that Lamtor5 is physically associated with ATP6V1A, an essential subunit of vacuolar H+‐ATPase (v‐ATPase), and promoted the V0/V1 holoenzyme assembly to facilitate lysosome acidification. The binding of Lamtor5 to v‐ATPase affected the lysosomal tethering of Rag GTPase and weakened its interaction with mTORC1 for activation. Overall, Lamtor5 is identified as a critical factor for immune homeostasis by intergrading v‐ATPase activity, lysosome function, and mTOR pathway. The findings provide a potential therapeutic target for SLE and/or other autoimmune diseases.

Abstract Metabolic abnormalities contribute to the pathogenesis of obesity and its complications. Yet, the understanding of the interactions between critical metabolic pathways that underlie obesity remains to be improved, in part owing to the lack of comprehensive metabolomics studies that reconcile data from both hydrophilic and lipophilic metabolome analyses that can lead to the identification and characterization of key signaling networks. Here, the study conducts a comprehensive metabolomics analysis, surveying lipids and hydrophilic metabolites of the plasma and omental adipose tissue of obese individuals and the plasma and epididymal adipose tissue of mice. Through these approaches, it is found that a significant accumulation of ceramide due to inhibited sphingolipid catabolism, while a significant reduction in the levels of uridine monophosphate (UMP), is critical to pyrimidine biosynthesis. Further, it is found that UMP administration restores sphingolipid homeostasis and can reduce obesity in mice by reversing obesity‐induced inhibition of adipocyte hypoxia inducible factor 2a (Hif2α) and its target gene alkaline ceramidase 2 (Acer2), so as to promote ceramide catabolism and alleviate its accumulation within cells. Using adipose tissue Hif2α‐specific knockout mice, the study further demonstrates that the presence of UMP can alleviate obesity through a HIF2α‐ACER2‐ceramide pathway, which can be a new signaling axis for obesity improvement.

Our previous study highlighted the therapeutic potential of glutathione (GSH), an intracellular thiol tripeptide ubiquitous in mammalian tissues, in mitigating hepatic and cerebral damage. Building on this premise, we posited the hypothesis that GSH could be a promising candidate for treating acute hepatic encephalopathy (AHE). To verify this conjecture, we systematically investigated the feasibility of GSH as a therapeutic agent for AHE through comprehensive pharmacokinetic, pharmacodynamic, and mechanistic studies using a thioacetamide-induced AHE rat model. Our pharmacodynamic data demonstrated that oral GSH could significantly improve behavioral scores and reduce hepatic damage of AHE rats by regulating intrahepatic ALT, AST, inflammatory factors, and homeostasis of amino acids. Additionally, oral GSH demonstrated neuroprotective effects by alleviating the accumulation of intracerebral glutamine, down-regulating glutamine synthetase, and reducing taurine exposure. Pharmacokinetic studies suggested that AHE modeling led to significant decrease in hepatic and cerebral exposure of GSH and cysteine. However, oral GSH greatly enhanced the intrahepatic and intracortical GSH and CYS in AHE rats. Given the pivotal roles of CYS and GSH in maintaining redox homeostasis, we investigated the interplay between oxidative stress and pathogenesis/treatment of AHE. Our data revealed that GSH administration significantly relieved oxidative stress levels caused by AHE modeling via down-regulating the expression of NADPH oxidase 4 (NOX4) and NF-κB P65. Importantly, our findings further suggested that GSH administration significantly regulated the excessive endoplasmic reticulum (ER) stress caused by AHE modeling through the iNOS/ATF4/Ddit3 pathway. In summary, our study uncovered that exogenous GSH could stabilize intracerebral GSH and CYS levels to act on brain oxidative and ER stress, which have great significance for revealing the therapeutic effect of GSH on AHE and promoting its further development and clinical application.

Out-of-hospital cardiac arrest is a major public health problem worldwide due to its high burden and poor outcomes. Despite progress in treatment, patient outcomes remain unsatisfactory, particularly in low-resource settings. The establishment of a registry is the first step towards gaining a comprehensive understanding of prevailing local conditions and identifying potential opportunities for improving patient survival. Here, we provide a narrative review of the BASeline Investigation of Out-of-hospital Cardiac Arrest (BASIC-OHCA), the first national OHCA registry in China, to introduce its development history, current state, challenges and future directions. We aim to enhance cross-cultural understanding by providing insights from China, while also serving as a reference for the implementation of large-scale registries in low-resource settings.

Nitrogen fertilizer levels significantly affect crop growth and development, necessitating precision management. Most studies focus on nitrogen nutrient estimation using vegetation indices and textural features, overlooking the diagnostic potential of color features. Hence, we investigated cotton nitrogen nutrition status using unmanned aerial vehicle (UAV) image features and the nitrogen nutrient index (NNI). Random frog algorithm - and random forest-screened image feature sets significantly correlated with the NNI, which were substituted into four machine learning algorithms for NNI estimation modeling. The composite scores (F) of optimal image feature sets were calculated using the coefficient of variation method for comprehensive cotton nitrogen nutrient diagnosis. Validation of the model for determining the critical nitrogen concentration in cotton yielded a coefficient of determination R2 = 0.89, root mean square error RMSE = 0.50 g (100 g)-1, and mean absolute error MAE = 0.44, demonstrating improved performance. Additionally, our novel NNI estimation model constructed based on the optimal image feature sets exhibited R2c = 0.97, RMSEc = 0.02, MAEc = 0.02, R2v = 0.85, RMSEv = 0.05, and MAEv = 0.04. Polynomial fitting of the composite index with NNI indicated that the model was reliable and yielded the following diagnostic criterion: 0.48 < F2 < 0.67 indicated nitrogen overapplication, whereas F2 < 0.48 or F2 > 0.67 indicated nitrogen deficiency. This study demonstrates the superior effectiveness of using UAV RGB image feature sets for NNI estimation and the quick, accurate diagnosis of cotton nitrogen levels, which will help guide nitrogen fertilizer application.

Abstract Non‐antibiotic strategies are desperately needed to treat post‐traumatic osteomyelitis (PTO) due to the emergence of superbugs, complex inflammatory microenvironments, and greatly enriched biofilms. Previously, growing evidence indicated that quorum sensing (QS), a chemical communication signal among bacterial cells, can accelerate resistance under evolutionary pressure. This study aims to develop a medical dressing to treat PTO by inhibiting QS and regulating the inflammatory microenvironment, which includes severe oxidative stress and acid abscesses, through a reactive oxygen species (ROS)‐responsive bond between N1‐ (4‐borobenzoyl)‐N3‐(4‐borobenzoyl)‐the N1, the N1, N3, N3‐tetramethylpropane‐1,3‐diamine (TSPBA) and polyvinyl alcohol (PVA), and the amino side chain of hyperbranched polylysine (HBPL). Physically enclosed QS inhibitors subsequently exerted the antibacterial effects. This hydrogel can scavenge hydrogen peroxide (H2O2), superoxide anion free radical (·O2−), hydroxyl radicals (·OH) and 2,2‐di(4‐tert‐octylphenyl)‐1‐picryl‐hydrazyl (DPPH) to reduce oxidative stress and inhibit “bacteria‐to‐bacteria communication”, thus clearing planktonic bacteria and biofilms, accelerating bacterial plasmolysis, reducing bacterial virulence and interfering with membrane transport. After in vivo treatment with hydrogel, nearly all bacteria are eliminated, inflammation is effectively inhibited, and osteogenesis and bone repair are promoted to facilitate recovery from PTO. The work demonstrates the clinical translational potential of the hydrogel in the treatment of drug‐resistant bacteria induced PTO.

IntroductionAlternol is a natural compound isolated from the fermentation of a mutated fungus. We have demonstrated its potent anti-cancer effect via the accumulation of radical oxygen species (ROS) in prostate cancer cells in vitro and in vivo. In this study, we tested its anti-cancer spectrum in multiple platforms.MethodsWe first tested its anti-cancer spectrum using the National Cancer Institute-60 (NCI-60) screening, a protein quantitation-based assay. CellTiter-Glo screening was utilized for ovarian cancer cell lines. Cell cycle distribution was analyzed using flow cytometry. Xenograft models in nude mice were used to assess anti-cancer effect. Healthy mice were tested for the acuate systemic toxicity.ResultsOur results showed that Alternol exerted a potent anti-cancer effect on 50 (83%) cancer cell lines with a GI50 less than 5 µM and induced a lethal response in 12 (24%) of those 50 responding cell lines at 10 µM concentration. Consistently, Alternol displayed a similar anti-cancer effect on 14 ovarian cancer cell lines in an ATP quantitation-based assay. Most interestingly, Alternol showed an excellent safety profile with a maximum tolerance dose (MTD) at 665 mg/kg bodyweight in mice. Its therapeutic index was calculated as 13.3 based on the effective tumor-suppressing doses from HeLa and PC-3 cell-derived xenograft models.ConclusionTaken together, Alternol has a broad anti-cancer spectrum with a safe therapeutic index in vivo.

Drug-resistant tuberculosis (TB), especially multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), is one of the urgent clinical problems and public health challenges. Culture-based phenotypic drug susceptibility testing (pDST) is time-consuming, and PCR-based assays are limited to hotspot mutations. In this study, we developed and validated a convenient and efficient approach based on high-throughput nanopore sequencing technology combined with multiplex PCR, namely nanopore targeted sequencing (NTS), to simultaneously sequence 18 genes associated with antibiotic resistance in Mycobacterium tuberculosis (MTB). The analytical performance of NTS was evaluated, and 99 clinical samples were collected to assess its clinical performance. The NTS results showed that MTB and its drug resistance were successfully identified in approximately 7.5 h. Furthermore, compared to the pDST and Xpert MTB/RIF assays, NTS provided much more drug resistance information, covering 14 anti-TB drugs, and it identified 20 clinical cases of drug-resistant MTB. The mutations underlying these drug-resistant cases were all verified using Sanger sequencing. Our approach for this TB drug resistance assay offers several advantages, including being culture-free, efficient, high-throughput, and highly accurate, which would be very helpful for clinical patient management and TB infection control.

Abstract Daily monitoring of psychological parameters, encompassing chemical and physical signals, has become increasingly valuable for the management of chronic diseases. Among various vital signs, carbon dioxide exchange and pulse rate (PR) serve as critical indicators for the comprehensive assessment of the cardiopulmonary system. However, simultaneous monitoring of these chemical and physical signals in a nonintrusive manner is challenging. This study presents a wearable bracelet that enables simultaneous monitoring of transcutaneous carbon dioxide (TcCO2) and PR using a nanomaterials‐modified lensless CMOS imager. The proposed bracelet exhibits exceptional sensitivity, selectivity, and anti‐humidity interference in TcCO2 detection, and achieves reliable tracking of TcCO2 and PR fluctuations induced by daily activities, demonstrating great potential in the comprehensive assessment of cardiopulmonary system. In addition, the proposed compact imaging approach is multiplexed and extensible, providing a promising sensing platform for the future development of multifunctional wearable devices.

ObjectiveThis study aimed to elucidate the therapeutic effects of Huaier granules on hepatocellular carcinoma (HCC) within the Milan criteria in patients who underwent microwave ablation (MWA).Materials and methodsA total of 228 patients were included, with 97 in the Huaier group and 131 in the control group. We evaluated progression-free survival (PFS), overall survival (OS), and extrahepatic metastasis survival (EMS) using Kaplan–Meier (KM) curves with a log-rank test. Propensity Score Matching (PSM) and Stabilized Inverse Probability of Treatment Weighting (IPTW) were performed to minimize selection and confounding biases.ResultsFollowing PSM, the 1-, 3-, and 5-year PFS rates in the Huaier and control groups were 83.5% vs 70.7%, 57.7% vs 42.6%, and 43.6% vs 31.9% (p = 0.030), respectively. The 1-, 3-, and 5-year OS rates were 98.9% vs 95.6%, 83.9% vs 72.3%, and 72.2% vs 53.7% (p = 0.023), respectively. The corresponding 1-, 3-, and 5-year EMS rates were 98.9% vs 93.4%, 91.7% vs 83.7%, and 91.7% vs 78.5% (p = 0.039), respectively. Stabilized IPTW analysis of KM curves yielded results similar to those of the PSM analysis. Additionally, administering Huaier granules for at least 6 months significantly improved PFS and OS.ConclusionHuaier granules can reduce the risk of recurrence and improve the OS of patients with HCC within the Milan criteria following MWA. Administering Huaier granules for over 6 months proved beneficial.

ObjectiveThis retrospective study aims to identify risk factors for urogenic sepsis in patients with upper urinary tract stones following ureteral flexible lithotripsy (FURL). Additionally, we analyze the clinical characteristics of bacterial infections post-surgery.MethodsA total of 759 patients who underwent FURL at the Urology Department of Zunyi Medical University were included. Univariate and multivariate Logistic regression analyses were conducted to identify independent risk factors for urogenic sepsis post-FURL. The distribution of bacteria based on preoperative urine cultures was also analyzed. Statistical analysis was performed using R4.2.2 software.ResultsOf the 759 patients, positive preoperative urine culture, urine nitrite positivity, urine white blood cell count (WBC) ≥ 200 cells/μL, residual stones, and neutrophil-to-lymphocyte ratio (NLR) were found to be independent risk factors for urogenic sepsis after FURL. Among the 164 patients with positive preoperative urine cultures, 32 developed urogenic sepsis post-surgery, with 68.75% having positive preoperative cultures. The leading pathogens causing postoperative urogenic sepsis were Escherichia coli (E. coli), Enterococcus faecium, Proteus mirabilis, and Klebsiella pneumoniae. The probabilities of progression to urogenic sepsis were as follows: E. coli 19% (n = 12), Enterococcus faecium 43% (n = 3), Proteus mirabilis 33.3% (n = 1), and Klebsiella pneumoniae 33.3% (n = 1). The ages of affected patients were 47.17 ± 13.2, 53.7, 41, and 79 years, respectively. Rates of comorbid diabetes were 36.4, 66.7, 50, 100%, with nitrite positivity rates at 72.7, 33.3, 50, 0%. Ten female patients were infected with E. coli, while patients infected with Klebsiella pneumoniae had an NLR of 7.62.ConclusionPositive preoperative urine culture, urine nitrite positivity, urine WBC ≥ 200 cells/μL, residual stones, and NLR are independent risk factors for urogenic sepsis after FURL. Escherichia coli is the predominant pathogen post-FURL, with notable female prevalence and nitrite-positive urine in infections. Enterococcus faecium infections are associated with diabetes.