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Abstract Background Although several studies have found the relationship between essential elements and diabetes, the studies about the association of essential elements with diabetes diagnosed according to an oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) in a sex- and age-specific manner were limited. To investigate the linear and nonlinear relationship of five essential elements including iron (Fe), copper (Cu), Zinc (Zn), magnesium (Mg), and calcium (Ca) with diabetes, fasting plasma glucose (FPG), 2-h postprandial plasma glucose (PPG), and HbA1c and to evaluate the sex- and age-specific heterogeneities in these relationships. Methods A total of 8392 community-dwelling adults were recruited to complete a questionnaire and undergo checkups of anthropometric parameters and serum levels of five metals (Fe, Cu, Zn, Mg, and Ca). The multivariable logistic and linear regression, the restricted cubic spline (RCS) analysis, and subgroup analysis were applied to find the associations between the essential elements and the prevalence of diabetes as well as FPG, PPG, and HbA1c. Results In the multivariable logistic regression and multivariable linear regression, serum Cu was positively associated with FPG, PPG, and HbA1c while serum Mg was significantly inversely correlated with FPG, PPG, HbA1c, and diabetes (all P

Abstract Background Cartilaginous endplate (CEP) degeneration, which is an important contributor to intervertebral disc degeneration (IVDD), is characterized by chondrocyte death. Accumulating evidence has revealed that dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and dysfunction lead to apoptosis during CEP degeneration and IVDD. Exosomes are promising agents for the treatment of many diseases, including osteoporosis, osteosarcoma, osteoarthritis and IVDD. Despite their major success in drug delivery, the full potential of exosomes remains untapped. Materials and methods In vitro and in vivo models of CEP degeneration were established by using lipopolysaccharide (LPS). We designed genetically engineered exosomes (CAP-Nrf2-Exos) expressing chondrocyte-affinity peptide (CAP) on the surface and carrying the antioxidant transcription factor nuclear factor E2-related factor 2 (Nrf2). The affinity between CAP-Nrf2-Exos and CEP was evaluated by in vitro internalization assays and in vivo imaging assays. qRT‒PCR, Western blotting and immunofluorescence assays were performed to examine the expression level of Nrf2 and the subcellular localization of Nrf2 and Drp1. Mitochondrial function was measured by the JC-1 probe and MitoSOX Red. Mitochondrial morphology was visualized by MitoTracker staining and transmission electron microscopy (TEM). After subendplate injection of the engineered exosomes, the degree of CEP degeneration and IVDD was validated radiologically and histologically. Results We found that the cargo delivery efficiency of exosomes after cargo packaging was increased by surface modification. CAP-Nrf2-Exos facilitated chondrocyte-targeted delivery of Nrf2 and activated the endogenous antioxidant defence system in CEP cells. The engineered exosomes inhibited Drp1 S616 phosphorylation and mitochondrial translocation, thereby preventing mitochondrial fragmentation and dysfunction. LPS-induced CEP cell apoptosis was alleviated by CAP-Nrf2-Exo treatment. In a rat model of CEP degeneration, the engineered exosomes successfully attenuated CEP degeneration and IVDD and exhibited better repair capacity than natural exosomes. Conclusion Collectively, our findings showed that exosome-mediated chondrocyte-targeted delivery of Nrf2 was an effective strategy for treating CEP degeneration. Graphic abstract CAP-Nrf2-Exos delivered Nrf2 into CEP cells and alleviated LPS-induced apoptosis by inhibiting Drp1-mediated mitochondrial fission

Abstract Background Toxoplasmosis is a zoonotic disease caused by the infection of the protozoa Toxoplasma gondii (T. gondii), and safe and effective therapeutic drugs are lacking. Mitochondria, is an important organelle that maintains T. gondii survival, however, drugs targeting mitochondria are lacking. Methods The cytotoxicity of BAM15 was detected by CCK-8 and the in vitro effects of BAM15 was detected by qPCR, plaque assay and flow cytometry. Furthermore, the ultrastructural changes of T. gondii after BAM15 treatment were observed by transmission electron microscopy, and further the mitochondrial membrane potential (ΔΨm), ATP level and reactive oxygen species (ROS) of T. gondii after BAM15 treatment were detected. The pharmacokinetic experiments and in vivo infection assays were performed in mice to determine the in vivo effect of BAM15. Results BAM15 had excellent anti-T. gondii activity in vitro and in vivo with an EC50 value of 1.25 μM, while the IC50 of BAM15 in Vero cells was 27.07 μM. Notably, BAM15 significantly inhibited proliferation activity of T. gondii RH strain and Prugniaud strain (PRU), caused T. gondii death. Furthermore, BAM15 treatment induced T. gondii mitochondrial vacuolation and autolysis by TEM. Moreover, the decrease in ΔΨm and ATP level, as well as the increase in ROS production further confirmed the changes Conclusions Our study identifies a useful T. gondii mitochondrial inhibitor, which may also serve as a leading molecule to develop therapeutic mitochondrial inhibitors in toxoplasmosis.’ Graphical Abstract

Objective This study aimed to assessing usability of intelligent guidance chatbots (IGCs) in Chinese hospitals. Methods A cross-sectional study based on expert survey was conducted between August to December 2023. The survey assessed the usability of chatbots in 590 Chinese hospitals. One-way ANOVA was used to analyze the impact of the number of functions, human-like characteristics, number of outpatients, and staff size on the usability of the IGCs. Results The results indicate that there are 273 (46.27%) hospitals scoring above 45 points. In terms of function development, 581(98.47%) hospitals have set the number of functions between 1 and 5. Besides, 350 hospitals have excellent function implementation, accounting for 59.32%. In terms of the IGC's human-like characteristic, 220 hospitals have both an avatar and a nickname. Results of One-way ANOVA show that, the number of functions( F = 202.667, P

The complex multistep electrochemical reactions of lithium polysulfides and the solid–liquid–solid phase transformation involved in the S8 to Li2S reactions lead to slow redox kinetics in lithium–sulfur batteries (Li–S batteries). However, some targeted researches have proposed strategies requiring the introduction of significant additional inactive components, which can seriously affect the energy density. Whereas polymer binders, proven to be effective in suppressing shuttle effects and constraining electrode volume expansion, also have promising potential in enhancing Li–S batteries redox kinetics. Herein, a novel aqueous polymer binder is prepared by convenient amidation reaction of fully biomaterials, utilizing its inherent rich amide groups for chemisorption and redox mediating ability of thiol groups to achieve adsorption redox-mediated synergism for efficient conversion of polysulfides. Li–S batteries based on N-Acetyl-L-Cysteine-Chitosan (NACCTS) binder exhibit high initial discharge specific capacity (1260.1 ​mAh ​g−1 at 0.2 ​C) and excellent cycling performance over 400 cycles (capacity decay rate of 0.018% per cycle). In addition, the batteries exhibit great areal capacity and stable capacity retention of 83.6% over 80 cycles even under high sulfur loading of 8.4 ​mg ​cm−2. This work offers a novel perspective on the redox-mediated functional design and provides an environmentally friendly biomaterials-based aqueous binder for practical Li–S battery.

Abstract Injectable biomaterials have garnered increasing attention for their potential and beneficial applications in minimally invasive surgical procedures and tissue regeneration. Extracellular matrix (ECM) hydrogels and porous synthetic polymer microspheres can be prepared for injectable administration to achieve in situ tissue regeneration. However, the rapid degradation of ECM hydrogels and the poor injectability and biological inertness of most polymeric microspheres limit their pro-regenerative capabilities. Here, we develop a biomaterial system consisting of elastic porous poly(l-lactide-co-ε-caprolactone) (PLCL) microspheres mixed with ECM hydrogels as injectable composites with interleukin-4 (IL-4) and insulin-like growth factor-1 (IGF-1) dual-release functionality. The developed multifunctional composites have favorable injectability and biocompatibility, and regulate the behavior of macrophages and myogenic cells following injection into muscle tissue. The elicited promotive effects on tissue regeneration are evidenced by enhanced neomusle formation, vascularization, and neuralization at 2-months post-implantation in a male rat model of volumetric muscle loss. Our developed system provides a promising strategy for engineering bioactive injectable composites that demonstrates desirable properties for clinical use and holds translational potential for application as a minimally invasive and pro-regenerative implant material in multiple types of surgical procedures.

Background: This study aimed to examine the associations of thyroid hormone sensitivity indices, including free triiodothyronine-to-free thyroxine (FT3/FT4) ratio, thyroid feedback quantile-based index by FT4 (TFQIFT4), thyroid-stimulating hormone index (TSHI), and thyrotrophic thyroxine resistance index (TT4RI) with all-cause mortality in euthyroid adults. Methods: The study included 6243 euthyroid adults from the National Health and Nutrition Examination Survey (NHANES) 2007–2012. FT3/FT4 ratio, TFQIFT4, TSHI, and TT4RI were calculated. The multivariable Cox proportional hazard regression, restricted cubic spline (RCS), and subgroup analysis were conducted. Results: Individuals in fourth quartile (Q4) had lower all-cause mortality than those in first quartile (Q1) of FT3/FT4 ratio (hazard ratio (HR): 0.70, 95% CI: 0.51, 0.94). Regarding TFQIFT4, individuals in Q4 of TFQIFT4 had a 43% higher all-cause mortality than those in Q1 (HR: 1.43, 95% CI: 1.05, 1.96) (P < 0.05, all). Compared with participants in Q1, no associations of TSHI and TT4RI with mortality were found. TFQIFT4 was linearly and positively associated with mortality. However, the FT3/FT4 ratio showed a U-shaped association with mortality. Conclusions: Increased risk for all-cause mortality was positively associated with TFQIFT4, suggesting that increased risk for all-cause mortality was associated with decreased central sensitivity to thyroid hormones. Furthermore, the FT3/ FT4 ratio showed a U-shaped association with mortality, with an inflection point at 0.5. However, more cohort studies are needed to validate the conclusions.

The development of the Energy Internet has improved the efficiency of energy utilization and promoted sustainable development of power and energy systems. The multi-energy system modeling considering the dynamic process of transmission line is one of the key research points of Energy Internet operation control. Through the energy circuit theory, the lumped parameter model of natural gas pipelines is built and the dynamic characteristic parameters under the control instruction are extracted. Combined with dynamic characteristic parameters, the long short-term memory (LSTM) neural network is designed to fit the natural gas pipeline dynamic process into discrete linear time-varying (LTV) equations. Combined with the equations, an energy hub method is used to build a control model of industrial parks with multi-energy distribution system. Using the rolling optimal control strategy given in this paper, the model is solved by the Matlab-Yalmip solver and rolling control instructions of each energy conversion unit are obtained. Finally, the case study demonstrates that the LSTM neural network-based modeling method presented in this paper can accurately fit the dynamic process of a natural gas pipeline system. The rolling control model of the multi-energy system can improve the efficiency of energy utilization, exhibit the transmission line status constraints during the optimization control process and improve reliability of the multi-energy system operation.

An adjustable gate driver is proposed based on the optimization of switching transient performances. The turn-on process is optimized through an adjustable charging current, while the turn-off process is optimized through an adjustable segmented drive current. The proposed gate drive circuit has the advantage of reducing switching loss, delay, and total switching time, while maintaining the switching stress and EMI noise level during both turn-on and turn-off transients. The proposed driver can be integrated into gate driver ICs, and the switching performance can be externally adjusted to match the power device for different applications. By combining the above techniques, an adjustable gate driver IC has been developed using the $0.25~\mu $ m BCD process. The simulated and experimental results validate the proposed technique. Compared to the conventional gate driver, the overshoot voltage has been reduced from 15.4% to 8.3%, and the overshoot current has decreased from 20.5% to 10.2% under a 10A load condition.

Abstract Ferroptosis is an iron-dependent form of regulated cell death driven by the lethal lipid peroxides. Previous studies have demonstrated that inducing ferroptosis holds great potential in cancer therapy, especially for patients with traditional therapy failure. However, cancer cells can acquire ferroptosis evasion during progression. To date, the therapeutic potential of inducing ferroptosis in bladder cancer (BCa) remains unclear, and whether a ferroptosis escape mechanism exists in BCa needs further investigation. This study verified that low pathological stage BCa cells were highly sensitive to RSL3-induced ferroptosis, whereas high pathological stage BCa cells exhibited obviously ferroptosis resistance. RNA-seq, RNAi-mediated loss-of-function, and CRISPR/Cas9 experiments demonstrated that ALOX5 deficiency was the crucial factor of BCa resistance to ferroptosis in vitro and in vivo. Mechanistically, we found that ALOX5 deficiency was regulated by EGR1 at the transcriptional level. Clinically, ALOX5 expression was decreased in BCa tissues, and its low expression was associated with poor survival. Collectively, this study uncovers a novel mechanism for BCa ferroptosis escape and proposes that ALOX5 may be a valuable therapeutic target and prognostic biomarker in BCa treatment.

Peripheral nerve injuries may result in severe long-gap interruptions that are challenging to repair. Autografting is the gold standard surgical approach for repairing long-gap nerve injuries but can result in prominent donor-site complications. Instead, imitating the native neural microarchitecture using synthetic conduits is expected to offer an alternative strategy for improving nerve regeneration. Here, we designed nerve conduits composed of high-resolution anisotropic microfiber grid-cordes with randomly organized nanofiber sheaths to interrogate the positive effects of these biomimetic structures on peripheral nerve regeneration. Anisotropic microfiber-grids demonstrated the capacity to directionally guide Schwann cells and neurites. Nanofiber sheaths conveyed adequate elasticity and permeability, whilst exhibiting a barrier function against the infiltration of fibroblasts. We then used the composite nerve conduits bridge 30-mm long sciatic nerve defects in canine models. At 12 months post-implant, the morphometric and histological recovery, gait recovery, electrophysiological function, and degree of muscle atrophy were assessed. The newly regenerated nerve tissue that formed within the composite nerve conduits showed restored neurological functions that were superior compared to sheaths-only scaffolds and Neurolac nerve conduit controls. Our findings demonstrate the feasibility of using synthetic biophysical cues to effectively bridge long-gap peripheral nerve injuries and indicates the promising clinical application prospects of biomimetic composite nerve conduits.

BackgroundPrevious studies have revealed the sex-specific features of pituitary–thyroid hormone (TH) actions and the prevalence of thyroid nodules (TNs) in children and adolescents. However, it was unclear in adults. We aimed to investigate the features of pituitary–TH actions in women and men at different ages, and the associations of thyrotropin (TSH), THs, and central sensitivity to THs indices including the thyroid feedback quantile-based index by FT4 (TFQIFT4) and the thyroid feedback quantile-based index by FT3(TFQIFT3) with of TNs in Chinese euthyroid adults.Methods8771 euthyroid adults from the communities in China were involved. Demographic, behavioral, and anthropometric data were gathered through the questionnaires. Ultrasound was performed to evaluate the TNs. TSH and THs levels were measured. The multivariable logistic regression and multivariable ordinal logistic regression were conducted.ResultsTFQIFT3 among both genders, except women aged 43 to 59 years, where it increased slightly. Additionally, there was an age-related decline in TFQIFT4 levels in both women and men at ages < 50 and < 53, respectively, but a marked increase after that. Lower TSH levels were significantly associated with a higher prevalence and lower odds of having fewer TNs using multiple nodules as the base category in both men and women (both P for trend < 0.05). Additionally, lower TFQIFT3 and TFQIFT4 levels were significantly associated with a higher prevalence of TNs in women (both P for trend < 0.05), and lower TFQIFT3 levels were significantly associated with a higher prevalence of TNs in men. Both higher TFQIFT3 and TFQIFT4 levels were significantly associated with higher odds of having fewer TNs using multiple nodules as the base category in women. However, the relationships between TFQIFT4 and the prevalence or number of TNs in men were not found.ConclusionsThe trends of THs, TSH, TFQIFT4, and TFQIFT3 at different ages were sex-dependent. Both TFQIFT4 and TFQIFT3 levels were negatively associated with the prevalence and number of TNs in women. The present results may lead to a better understanding of the sex-specific relationships between the development of the pituitary-TH axis and the formation of TNs.

BackgroundMetabolic syndrome (MetS) and sarcopenia (SP) have emerged as significant public health concerns in contemporary societies, characterized by shared pathophysiological mechanisms and interrelatedness, leading to profound health implications. In this prospective cohort study conducted within a US population, we aimed to examine the influence of MetS and SP on all-cause and cardiovascular mortality.MethodsThis study analyzed data from the National Health and Nutrition Examination Survey (NHANES) III for the years 1999-2006 and 2011-2018, and death outcomes were ascertained by linkage to National Death Index (NDI) records through December 31, 2019. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause and cardiovascular mortality. In addition, subgroup and sensitivity analyses were conducted to test the robustness of the results.ResultsOver a median follow-up period of 13.3 years (95% CI: 12.8-13.8), 1714 deaths were observed. The groups characterized by MetS−/SP+, MetS+/SP−, and MetS+/SP+ exhibited higher all-cause mortality rates in comparison to the MetS-/SP- group, with the MetS+/SP+ group (HR 1.76, 95% CI: 1.37-2.25) displaying the highest all-cause mortality. Increased cardiovascular mortality was observed in the MetS+/SP− (HR 1.84, 95% CI: 1.24-2.72), and MetS+/SP+ groups (HR 2.39, 95% CI: 1.32-4.35) compared to the MetS−/SP− group, whereas it was not statistically significant in the MetS-/SP+ group. However, among males and individuals aged < 60, the presence of both MetS and SP (MetS+/SP+ group) was found to be significantly associated with a higher risk of all-cause and cardiovascular mortality.ConclusionThe coexistence of MetS and SP increased the risk of all-cause and cardiovascular mortality, particularly in males and in nonelderly populations. Individuals with either MetS or SP may require more careful management to prevent the development of other diseases and thereby reduce mortality.

Abstract Antineutrophil cytoplasmic autoantibody (ANCA)‐associated vasculitis (AAV) is a rare and severe systemic autoimmune disease characterized by pauci‐immune necrotizing inflammation of small blood vessels. AAV involves multiple organ systems throughout the body. Our knowledge of the pathogenesis of AAV has increased considerably in recent years, involving cellular, molecular and genetic factors. Because of the controlled environment with no other confounding factors, animal models are beneficial for studying the mechanistic details of disease development and for providing novel therapeutic targets with fewer toxic side effects. However, the complexity and heterogeneity of AAV make it very difficult to establish a single animal model that can fully represent the entire clinical spectrum found in patients. The aim of this review is to overview the current status of animal models for AAV, outline the pros and cons of methods, and propose potential directions for future research.

Abstract Integrating corpus linguistic analysis with news values, this article investigates how the Covid-19 pandemic in different countries is represented as newsworthy by China Daily (CD) and The New York Times (NYT), two news outlets with different cultural and political backgrounds. A distinction is made between reports on the pandemic in the newspaper’s home country and reports on the pandemic in other countries. Three corpus linguistic techniques, i.e., keywords list, collocation, and concordance, are used to analyze the headlines and leads of 2572 news reports published in 2020 and 2021. Analysis results show that when presenting the pandemic in domestic news, CD tends to highlight Proximity, Positivity, and Personalization, whereas NYT gives more prominence to Eliteness and Personalization. When the pandemic in other countries is presented, CD foregrounds Negativity, Impact, Superlativeness, and Eliteness, whereas NYT focuses on Negativity, Impact, and Proximity. Compared with NYT, CD shows a stronger tendency to adopt positive self-representation and negative other-representation in its coverage of the Covid-19 pandemic. Apart from the analysis results, the significance of the study also lies in its demonstration of the applicability of a corpus linguistic approach to news values analysis.

Abstract Ischemic stroke is a leading cause of global mortality and long-term disability. However, there is a paucity of whole-genome sequencing studies on ischemic stroke, resulting in limited knowledge of the interplay between genomic and phenotypic variations among affected patients. Here, we outline the STROMICS design and present the first whole-genome analysis on ischemic stroke by deeply sequencing and analyzing 10,241 stroke patients from China. We identified 135.59 million variants, > 42% of which were novel. Notable disparities in allele frequency were observed between Chinese and other populations for 89 variants associated with stroke risk and 10 variants linked to response to stroke medications. We investigated the population structure of the participants, generating a map of genetic selection consisting of 31 adaptive signals. The adaption of the MTHFR rs1801133-G allele, which links to genetically evaluated VB9 (folate acid) in southern Chinese patients, suggests a gene-specific folate supplement strategy. Through genome-wide association analysis of 18 stroke-related traits, we discovered 10 novel genetic-phenotypic associations and extensive cross-trait pleiotropy at 6 lipid-trait loci of therapeutic relevance. Additionally, we found that the set of loss-of-function and cysteine-altering variants present in the causal gene NOTCH3 for the autosomal dominant stroke disorder CADASIL displayed a broad neuro-imaging spectrum. These findings deepen our understanding of the relationship between the population and individual genetic layout and clinical phenotype among stroke patients, and provide a foundation for future efforts to utilize human genetic knowledge to investigate mechanisms underlying ischemic stroke outcomes, discover novel therapeutic targets, and advance precision medicine.

The aim of this study was to investigate the effect of neutral protease treatment on the biochemical properties of various parts of Pacific oysters (Crassostrea gigas) under different storage conditions. The mechanism of quality degradation in the mantle, adductor muscle, gill, and trunk of treated oysters stored at −1.5 °C (superchilling) or 4 °C (refrigeration) for several days using different storage methods was studied. The results showed that the oyster treated with the enzyme exhibited higher glycogen content, flavor nucleotide content, and sensory scores compared to the control group. Superchilling at −1.5 °C was observed to slow the increase in total volatile basic nitrogen (TVB-N), total viable count (TVC), and pH, while maintaining sensory scores better than refrigeration at 4 °C. Both wet superchilling (WS) and dry exposed superchilling (DeS) methods effectively preserved freshness and quality at −1.5 °C. The freshness of the oysters’ body trunk changed most significantly. K value, K′ value, and AEC value, as the evaluation indexes of oyster freshness, were affected by the storage medium. Therefore, neutral protease enhances the flavor of oysters in a short time, and oysters stored in wet superchilling or dry exposed superchilling conditions have an extended shelf life.

Toxoplasmosis is a widespread disease in humans and animals. Currently, toxoplasmosis chemotherapy options are limited due to severe side effects. There is an urgent need to develop new drugs with better efficacy and few side effects. HQNO, a cytochrome bc1 and type II NADH inhibitor in eukaryotes and bacteria, possesses extensive bioactivity. In this study, the cytotoxicity of HQNO was evaluated in Vero cells. The in vitro effects of HQNO were determined by plaque assay and qPCR assay. To determine the in vivo effect of HQNO, pharmacokinetic experiments and in vivo infection assays were performed in mice. The changes in tachyzoites after HQNO exposure were examined by transmission electron microscopy (TEM), MitoTracker Red CMXRos staining, ROS detection and ATP detection. HQNO inhibited T. gondii invasion and proliferation with an EC50 of 0.995 μM. Pharmacokinetic experiments showed that the Cmax of HQNO (20 mg/kg·bw) was 3560 ± 1601 ng/mL (13.73 μM) in healthy BALB/c mouse plasma with no toxicity in vivo. Moreover, HQNO induced a significant decrease in the parasite burden load of T. gondii in mouse peritoneum. TEM revealed alterations in the mitochondria of T. gondii. Further assays verified that HQNO also decreased the mitochondrial membrane potential (ΔΨm) and ATP levels and enhanced the level of reactive oxygen species (ROS) in T. gondii. Hence, HQNO exerted anti-T. gondii activity, which may be related to the damage to the mitochondrial electron transport chain (ETC).

Abstract Stage III non‐small cell lung cancer (NSCLC) encompasses a group of diseases with high heterogeneity. Such patients should actively receive comprehensive treatments. It is imperative for all stage III NSCLC patients to receive consultation with a multiple disciplinary team, which allows the development of a proposal for clinical diagnosis and treatment. In this consensus, stage III NSCLC is divided into two types (operable and inoperable) according to different clinical conditions. Resectable NSCLC is further subdivided into two conditions (with or without driver genes). For each clinical scenario, this consensus emphasizes that the foundation of any medical decisions regarding the optimal diagnostic or therapy procedure is scientific evidence from clinical research. Finally, based on the level of evidence and strength of recommendations, this consensus provides recommendations for the management of stage III NSCLC from six perspectives. The objective of this consensus is to help clinicians choose the best treatment and promote the standardization of stage III NSCLC diagnosis and treatment in China.

Abstract Due to the rise of 5G, IoT, AI, and high-performance computing applications, datacenter traffic has grown at a compound annual growth rate of nearly 30%. Furthermore, nearly three-fourths of the datacenter traffic resides within datacenters. The conventional pluggable optics increases at a much slower rate than that of datacenter traffic. The gap between application requirements and the capability of conventional pluggable optics keeps increasing, a trend that is unsustainable. Co-packaged optics (CPO) is a disruptive approach to increasing the interconnecting bandwidth density and energy efficiency by dramatically shortening the electrical link length through advanced packaging and co-optimization of electronics and photonics. CPO is widely regarded as a promising solution for future datacenter interconnections, and silicon platform is the most promising platform for large-scale integration. Leading international companies (e.g., Intel, Broadcom and IBM) have heavily investigated in CPO technology, an inter-disciplinary research field that involves photonic devices, integrated circuits design, packaging, photonic device modeling, electronic-photonic co-simulation, applications, and standardization. This review aims to provide the readers a comprehensive overview of the state-of-the-art progress of CPO in silicon platform, identify the key challenges, and point out the potential solutions, hoping to encourage collaboration between different research fields to accelerate the development of CPO technology. Graphical Abstract

The inertness of synthetic polymer materials and the insufficient mechanical strength of reprocessed decellularized extracellular matrix (dECM) limited their promotive efforts on tissue regeneration. Here, we prepared a hybrid scaffold composed of PCL microfibers and human placental extracellular matrix (pECM) nanofibers by co-electrospinning, which was grafted with heparin and further absorbed with IL-4. The hybrid scaffold with improved hemocompatibility firstly switched macrophages to anti-inflammatory phenotype (increased by 18.1%) and then promoted migration, NO production, tube formation of endothelial cells (ECs), and migration and maturation of vascular smooth muscle cells (VSMCs), and ECM deposition in vitro and in vivo. ECs coverage rate increased by 8.6% and the thickness of the smooth muscle layer was 1.8 times more than PCL grafts at 12 wks. Our study realized the complementary advantages of synthetic polymer materials and dECM materials, and opened intriguing perspectives for the design and construction of small-diameter vascular grafts (SDVGs) and immune-regulated materials for other tissue regeneration.

Summary: Exploring key genes for antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN) is of great significance. Through bioinformatics analysis, 79 immune protein-differentially expressed genes (IP-DEGs) were obtained. Six hub genes (PTPRC, CD86, TLR2, IL1B, CSF-1R, and CCL2) were identified and verified to be increased in ANCA-GN patients. Random forest algorithm and ROC analysis showed that CSF-1R was a potential biomarker. Plasma CSF-1R levels increased significantly in ANCA-GN-active patients compared with remission stage and control. Correlation analysis revealed that CSF-1R levels had positive relationship with serum creatinine and Birmingham scoring, while inversely correlated with eGFR. Multivariate analysis revealed that plasma CSF-1R were an independent poor prognostic variable for end-stage renal disease or death, after adjusting for age and gender (HR = 3.05, 95% CI = 1.45–6.43, p = 0.003). Overall, we revealed that the CSF-1R is related to disease activity and might be a vital gene associated with the pathogenesis of ANCA-GN.

Abstract Lithium–sulfur (Li–S) batteries are the promising next‐generation secondary energy storage systems, because of their advantages of high energy density and environmental friendliness. Among numerous cathode materials, organosulfur polymer materials have received extensive attentions because of their controllable structure and uniform sulfur distribution. However, the sulfur content of most organosulfur polymer cathodes is limited (S content

Easy inter-connection is a crucial advantage of the single-chip power ICs, which makes power devices with multiple ports easy to improve carrier controllability without increasing process difficulty. Electrical characteristics of the power devices get further improved thanks to the advanced carrier controllability. In this paper, a silicon-on-isolator lateral IGBT (SOI-LIGBT) featured four hybrid gates is proposed to obtain outstanding carrier controllability in turn-on, turn-off and short-circuit conditions for the first time. Four hybrid gates include three planar gates (G1, G2 and G3) and a trench gate (G4), of which G3 and G4 are grounded gate to lower saturation current and suppress latch up. Low turn-off time $(t_{OFF})$ , di/dt and improved short-circuit withstanding capability are obtained through providing different input signals to these gates. In the turn-on, G2 is pre-charged to a stable voltage equal to gate voltage $(V_{G1})$ to suppress the high di/dt before $V_{G1}$ starts to rise. In the turn-off, a P-type inversion is induced by the negative voltage of ${\mathrm{ G}}_{2}~(V_{G2})$ , which provides a low-resistance hole current path to extract the stored holes. In the short-circuit condition, G3 and G4 are both shorted to the ground to lower the saturation current and suppress the activation of parasitic NPN transistor, resulting in an improved short-circuit withstanding time $(t_{SC})$ . Compared with the conventional SOI-LIGBT, $t_{OFF}$ and di/dt are reduced by 43.6% and 53.08%, and $t_{SC}$ is prolonged from $3.04\mu \text{s}$ to $8.89\mu \text{s}$ at DC bus voltage of 400V.

Abstract Background Spinal cord injury (SCI) brings a heavy burden to individuals and society, and there is no effective treatment at present. Exosomes (EX) are cell secreted vesicles containing molecules such as nucleic acids and proteins, which hold promise for the treatment of SCI. Netrin-1 is an axon guidance factor that regulates neuronal growth. We investigated the effects of engineered EX enriched in netrin-1 chemically synthetic modified message RNA (modRNA) in treating SCI in an attempt to find a novel therapeutic approach for SCI. Methods Netrin-1 modRNA was transfected into bone marrow mesenchymal stem cells to obtain EX enriched with netrin-1 (EX-netrin1). We built an inflammatory model in vitro with lipopolysaccharide (LPS) in vitro to study the therapeutic effect of EX-netrin1 on SCI. For experiments in vitro, ELISA, CCK-8 assay, immunofluorescence staining, lactate dehydrogenase release experiments test, real-time quantitative polymerase chain reaction, and western blot were conducted. At the same time, we constructed a rat model of SCI. MRI, hematoxylin-eosin and Nissl staining were used to assess the extent of SCI in rats. Results In vitro experiments showed that EX had no effect on the viability of oligodendrocytes and PC12 cells. EX-netrin1 could attenuate LPS-induced inflammation and pyroptosis and accelerate axonal/dentritic growth in PC12 cells/oligodendrocytes. In addition, netrin-1 could activate the PI3K/AKT/mTOR signalling pathway upon binding to its receptor unc5b. When Unc5b and PI3K were inhibited, the effect of EX-netrin1 was weakened, which could be reversed by PI3K or mTOR activator. Our in vivo experiments indicated that EX-netrin1 could promote recovery in rats with SCI. Conclusion We found that EX-netrin1 regulated inflammation, pyroptosis and axon growth in SCI via the Unc5b/PI3K/AKT/mTOR pathway, which provides a new strategy for the treatment of SCI.

Silicon carbide particle-reinforced aluminum matrix composites (SiCp/Al) find diverse applications in engineering. Nevertheless, SiCp/Al exhibit limited machinability due to their special structure. A pulsed laser ultrasonic vibration assisted cutting (PLUVAC) method was proposed to enhance the machining characteristics of SiCp/Al and decrease surface defects. The finite element model was constructed, considering both the thermal effect of the pulsed laser and the location distribution of SiC particles. The model has been developed to analyze the damage forms of SiC particles and the formation mechanisms for the surface morphology. The influence of pulsed laser power on average cutting forces has also been analyzed. Research results indicate that PLUVAC accelerates the transition from the brittleness to the plastic of SiC particles, which helps to reduce surface scratching caused by fragmented SiC particles. Furthermore, the enhancement of surface quality is attributed to the decrease in surface cracks and the beneficial coating effect of the Al matrix. The accuracy of the simulation is verified by experiments, and the feasibility of PLUVAC method to enhance the surface quality of SiCp/Al is confirmed.

IntroductionAlthough several studies have explored the associations between single essential metals and serum uric acid (SUA), the study about the essential metal mixture and the interactions of metals for hyperuricemia remains unclear.MethodsWe performed a cross-sectional study to explore the association of the SUA levels with the blood essential metal mixture, including magnesium (Mg), calcium (Ca), iron (Fe), copper (Cu), zinc (Zn), manganese (Mn) in Chinese community-dwelling adults (n=1039). The multivariable linear regression, the weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were conducted to estimate the associations of blood essential metals with SUA levels and the BKMR model was also conducted to estimate the interactions of the essential metals on SUA.ResultsIn the multivariable linear regression, the association of blood Mg, Mn, and Cu with SUA was statistically significant, both in considering multiple metals and a single metal. In WQS regression [β=13.59 (95%CI: 5.57, 21.60)] and BKMR models, a positive association was found between the mixture of essential metals in blood and SUA. Specifically, blood Mg and Cu showed a positive association with SUA, while blood Mn showed a negative association. Additionally, no interactions between individual metals on SUA were observed.DiscussionIn conclusion, further attention should be paid to the relationship between the mixture of essential metals in blood and SUA. However, more studies are needed to confirm these findings.

Objective The association of appendicular skeletal muscle mass (ASM), grip strength and fat-to-muscle ratio (FMR) and the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) are not well known.Materials and methods This study included participants older than 40 years who underwent bioelectrical impedance assessment in Prevalence of Metabolic Diseases and Risk Factors in Shunde (SPEED-Shunde). We measured grip strength with an electronic grip strength metre. ASM and grip strength were adjusted by dividing body mass index (BMI). FMR was calculated as total fat mass to total muscle mass. Liver steatosis and liver fibrosis were evaluated by vibration-controlled transient elastography. Multifactorial logistic regression was used to analyse the relationship between ASM, grip strength, FMR, and MASLD or MASLD-associated liver fibrosis. We performed subgroup analyses according to sex, age and BMI. Interaction tests and linear trend tests were also conducted.Results This study included a total of 3277 participants. FMR was positively associated with MASLD (OR: 1.89, 95% CI: 1.66–2.15) and MASLD-associated liver fibrosis (OR: 1.70, 95% CI: 1.22–2.37). While ASM/BMI (OR: 0.59, 95% CI: 0.52–0.67) or grip strength/BMI (OR: 0.72, 95% CI: 0.66–0.78) were negatively associated with MASLD. Interactions were observed between ASM/BMI and age, grip strength and sex in MASLD, as well as FMR and MASLD-associated liver fibrosis.Conclusion In a middle-to-elderly aged population, FMR was positively associated with the risk of MASLD and MASLD-associated liver fibrosis, and muscle mass and grip strength were negatively associated with MASLD, rather than MASLD-associated liver fibrosis.

Kounis syndrome is an acute coronary syndrome triggered by allergic mediators that induce coronary vasoconstriction and thrombosis, leading to further myocardial damage and anaphylactic shock. Kounis syndrome is also a rare but severe adverse reaction to the COVID-19 vaccine, a phenomenon that underscores the importance of collecting and analyzing similar cases to improve treatment and prognosis. Through comprehensive searches of the Web of Science, Embase, and PubMed databases, this study aimed to gather detailed patient data on patients who developed Kounis syndrome after receiving the COVID-19 vaccine and to further investigate the possible underlying mechanisms using currently available studies. A total of 15 patients (8 females, 7 males) were found. We analyzed comprehensive patient data, including demographics, vaccination details, time of onset of illness after vaccination, clinical manifestations, treatment and outcomes, duration of illness, and relevant examination results. Analysis of these data combined with known allergy-related mechanisms indicated that, regardless of the vaccine type, the first dose of the vaccine was more likely to cause Kounis syndrome than subsequent doses. Therefore, early diagnosis and clinical symptomatic treatment are particularly crucial for managing the severity of Kounis syndrome and preventing further cardiac complications. Additionally, when an unusual and severe allergic reaction occurs within a few hours after vaccination, it is important to closely monitor the development of cardiac-related symptoms and prepare clinically for the potential onset of Kounis syndrome.

AbstractBackground We aimed to investigate the associations between thyroid hormone sensitivity indices and diabetes in euthyroid adults in the United States and China.Methods 2296 euthyroid adults from the NHANES in the United States and 8319 euthyroid adults from the SPEED-Shunde in China were involved. The thyroid sensitivity indices, namely TFQIFT4 and TFQIFT3, were calculated. Multivariable logistic regression, restricted cubic spline analysis, and general ordinal logit regression were utilized.Results In the NHANES, compared with participants in quartile 1st (Q1), those in Q4 of TFQIFT3 (OR 2.12, 95% CI (1.18, 3.81)) and those in Q3 of TFQIFT4 (OR 2.31, 95% CI (1.18, 4.53)) (both P for trend < 0.05) were associated with a greater prevalence of diabetes. In the SPEED-Shunde, compared with participants in Q1, those in Q4 of TFQIFT3 had a greater prevalence of diabetes (OR 1.36, 95% CI (1.11, 1.66) (P for trend < 0.05), while no significant associations between TFQIFT4 and diabetes were found.Conclusions TFQIFT3 was associated with a higher prevalence of diabetes both in the United States and China. However, TFQIFT4 was only associated with a higher prevalence of diabetes in the United States, not in China. Further prospective cohort studies are necessary to validate these findings.

Abstract Background The quantity and quality of the paraspinal muscles are important factors that lead to spinal diseases. However, the role of paraspinal muscles in the pathogenesis of adjacent segment disease (ASD) after lumbar fusion surgery is rarely studied. The purpose of the research is to investigate the relationship between paraspinal muscles and ASD. Methods Thirty-three patients with ASD were included, and 33 controls without ASD were matched according to the basic demographic information. Cross-sectional images of the paraspinal muscles at each intervertebral disk level (L1–S1) before the first operation were analyzed, and the cross-sectional area (CSA) and degree of fat infiltration (FI) of the multifidus (MF) muscle and the erector spinae muscle were compared. Results There was no significant difference in demographic characteristics (P > 0.05) except for the bone mineral density (BMD) (P = 0.037) between the two groups. There were significant differences in the CSA and FI of the lower lumbar multifidus (P

Functional plant polysaccharides are macromolecular carbohydrates produced by the metabolism of plant cells, which are macromolecular carbohydrates formed by the polymerization of more than 10, or hundreds or even thousands of monosaccharide molecules through glycosidic bonds; It has a variety of biological activities such as blood lipids, immune regulation, anti-tumor, and intestinal microecology regulation. It also has the advantages of wide sources, safety and non-toxicity, high activity, and high environmental affinity. It has broad application prospects in the field of food and biomedicine. This paper mainly reviews the relevant research progress of plant polysaccharides in terms of structure analysis, extraction methods, immunomodulation, anti-tumor, antioxidant, anti-aging, hypoglycemic and hypolipidemic activities and their application as functional factors, in order to provide reference and reference for scholars' research and further development and utilization.

Abstract Hard carbons are promising anodes for sodium‐ion batteries. However, there is still considerable controversy regarding the sodium storage behaviors in hard carbons, which are mainly attributed to the varied precursors, confused pyrolysis mechanism, and different characterization methods. Herein, benefiting from the flexible molecular structure of polymers, a series of hard carbons with carefully tuned microstructures are fabricated by adjusting the ratio of aryl and alkyl groups in the epoxy resins. The results of dynamic mechanical analysis, in‐situ Fourier transform infrared spectra, and synchronous thermal gravimetric‐infrared spectrum‐gas chromatography/mass spectrometry reveal that replacing the alkyl with aryl groups in the resin can enhance the crosslink density, inhibit the degradation and rearrangement process, and further lead to a more disordered microstructure. In addition, it is suggested that accessible channels provided by sufficiently wide interlayer spacing are necessary for closed pore filling. The optimized anode delivers a high capacity of 375 mAh/g in half cell with an initial Coulombic efficiency of 80.61%, and an energy density of 252 Wh/kg is attained in full cell. Finally, a reliable relationship among precursor–pyrolysis mechanism–structure–performance is established, and the sodium storage mechanism of “adsorption–insertion–pore filling” is well proved.

Background Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune systemic disease, and the majority of AAV patients have renal involvement presenting as rapid progressive glomerulonephritis (GN). Currently, the clinically available AAV markers are limited, and some of the newly reported markers are still in the nascent stage. The particular mechanism of the level changes of various markers and their association with the pathogenesis of AAV are not well defined. With the help of metabolomics analysis, this study aims to explore metabolic changes in AAV patients with renal involvement and lay the foundation for the discovery of novel biomarkers for AAV-related kidney damage. Methods We performed liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based on serum samples from patients with AAV (N = 33) and healthy controls (N = 33) in order to characterize the serum metabolic profiling. The principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA) were used to identify the differential metabolites. Least Absolute Shrinkage and Selection Operator (LASSO) and eXtreme Gradient Boosting (XGBoost) analysis were further conducted to identify the potential diagnostic biomarker. A receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic performance of the identified potential biomarker. Results A total of 455 metabolites were detected by LC-MS analysis. PCA and OPLS-DA demonstrated a significant difference between AAV patients with renal involvement and healthy controls, and 135 differentially expressed metabolites were selected, with 121 upregulated and 14 downregulated. Ninety-two metabolic pathways were annotated and enriched based on the KEGG database. N-acetyl-L-leucine, Acetyl-DL-Valine, 5-hydroxyindole-3-acetic acid, and the combination of 1-methylhistidine and Asp-phe could accurately distinguish AAV patients with renal involvement from healthy controls. And 1-methylhistidine was found to be significantly associated with the progression and prognosis of AAV with renal impairment. Amino acid metabolism exhibits significant alternations in AAV with renal involvement. Conclusion This study identified metabolomic differences between AAV patients with renal involvement and non-AAV individuals. Metabolites that could accurately distinguish patients with AAV renal impairment from healthy controls in this study, and metabolites that were significantly associated with disease progression and prognosis were screened out. Overall, this study provides information on changes in metabolites and metabolic pathways for future studies of AAV-related kidney damage and lays a foundation for the exploration of new biomarkers of AAV-related kidney damage.

IntroductionCoronavirus disease 2019 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Influential variants and mutants of this virus continue to emerge, and more effective virus-related information is urgently required for identifying and predicting new mutants. According to earlier reports, synonymous substitutions were considered phenotypically silent; thus, such mutations were frequently ignored in studies of viral mutations because they did not directly cause amino acid changes. However, recent studies have shown that synonymous substitutions are not completely silent, and their patterns and potential functional correlations should thus be delineated for better control of the pandemic.MethodsIn this study, we estimated the synonymous evolutionary rate (SER) across the SARS-CoV-2 genome and used it to infer the relationship between the viral RNA and host protein. We also assessed the patterns of characteristic mutations found in different viral lineages.ResultsWe found that the SER varies across the genome and that the variation is primarily influenced by codon-related factors. Moreover, the conserved motifs identified based on the SER were found to be related to host RNA transport and regulation. Importantly, the majority of the existing fixed-characteristic mutations for five important virus lineages (Alpha, Beta, Gamma, Delta, and Omicron) were significantly enriched in partially constrained regions.DiscussionTaken together, our results provide unique information on the evolutionary and functional dynamics of SARS-CoV-2 based on synonymous mutations and offer potentially useful information for better control of the SARS-CoV-2 pandemic.

IntroductionBladder cancer (BLCA) is a highly malignant tumor of the urinary system, but the prognosis and survival rates have little improvement based on current therapeutic strategy. Immune checkpoint inhibitors (ICIs) therapy revolutionized the treatment of BLCA, but the clinical application of ICIs is limited by low response rate. Oxaliplatin (OXP), a second line chemotherapy drug for BLCA, may reshape the tumor immune microenvironment (TIME) via recruiting immune cells. Here, we conducted the study of oxaliplatin combined with anti-PD-1 inhibitor in BLCA mice models.MethodsThe 6-8 weeks old female C57BL/6J mice were used to establish subcutaneous model of bladder tumor. After tumors developed, mice were given tail vein injections of PBS or oxaliplatin (2.5 mg/kg) and/or anti-PD-1 antibody (10 mg/kg). Tumor tissue samples and peripheral blood mononuclear cell (PBMC) were collected to systemically evaluate the efficiency and safety of combination OXP and anti-PD-1 inhibitor. The change of immune cells populations and the corresponding phenotypic diversity in TIME and PBMC were analysed by flow cytometry.ResultsTumor growth experiments clarified that the combination therapy was more efficient than medication alone. Flow cytometry analysis of tumor samples showed significant differences between untreated and treated mice. Oxaliplatin influences the TIME by increasing immune cells infiltration, including CD3+ T cells, CD4+ T cells, CD8+ T cells, dendritic cells (DC cells) and natural killer cells (NK cells). As for infiltrating cells, oxaliplatin upregulated the expression of CD134 and downregulated TIM-3 of CD4+ T cells, downregulated the PD-L1 expression of DC cells, which contributed to improve the anti-tumor effect and the treatment response of ICIs. Additionally, the evaluation of PBMC found that there were no significant changes in immune cell subsets and phenotypes, which validated the safety of the combination therapy. These results show the therapeutic potential for the combination of OXP and anti-PD-1 inhibitor in BLCA.ConclusionOXP could increase the infiltration of immune cells in TIME to promote the anti-tumor activity of anti-PD-1 inhibitor. The present research provided an appropriate rationale of combination chemotherapy and immunotherapy therapy for BLCA.

Objectives: To analyze the correlations between the expression and effect of DNA damage repair genes and the immune status and clinical outcomes of urothelial bladder cancer (BLCA) patients. In addition, we evaluate the efficacy and value of utilizing the DNA damage repair genes signature as a prognosis model for BLCA. Methods: Two subtype groups (C1 and C2) were produced based on the varied expression of DNA damage repair genes. Significantly differentiated genes and predicted enriched gene pathways were obtained between the two subtypes. Seven key genes were obtained from the DNA damage repair-related genes and a 7-gene signature prognosis model was established based on the key genes. The efficacy and accuracy of this model in prognosis prediction was evaluated and verified in two independent databases. Also, the difference in biological functions, drug sensitivity, immune infiltration and affinity between the high-risk group and low-risk group was analyzed. Results: The DNA damage repair gene signature could significantly differentiate the BLCA into two molecular subgroups with varied genetic expression and enriched gene pathways. Seven key genes were screened out from the 232 candidate genes for prognosis prediction and a 7-gene signature prognosis model was established based on them. Two independent patient cohorts (TCGA cohort and GEO cohort) were utilized to validate the efficacy of the prognosis model, which demonstrated an effective capability to differentiate and predict the overall survival of BLCA patients. Also, the high-risk group and low-risk group derived from the 7-gene model exhibited significantly differences in drug sensitivity, immune infiltration status and biological pathways enrichment. Conclusions: Our established 7-gene signature model based on the DNA damage repair genes could serve as a novel prognosis predictive tool for BLCA. The differentiation of BLCA patients based on the 7-gene signature model may be of great value for the appropriate selection of specific chemotherapy agents and immune-checkpoint blockade therapy administration.

Though the coronavirus disease is still raging in 2021, clinical research on non-small cell lung cancer (NSCLC) did not stop. However, benefiting from advances in lung cancer treatment modality, NSCLC patients have experienced significant improvements in overall survival and quality of life. Currently, research advances on targeted therapy and immunotherapy have together transformed the status of postoperative adjuvant therapy and established a new standard treatment modality for resectable NSCLC. There are equally important research advances in locally advanced and advanced NSCLC, including new treatment modalities, new therapeutic agents, etc., all of which bringing more options for clinical treatment. These therapies will bring changes to NSCLC and will gradually lead to the chronicity of lung cancer in the foreseeable future. Therefore, this paper reviews important studies that will change clinical practice in NSCLC treatment and noteworthy research advances in 2021.

TP53 (or p53) is widely accepted to be a tumor suppressor. Upon various cellular stresses, p53 mediates cell cycle arrest and apoptosis to maintain genomic stability. p53 is also discovered to suppress tumor growth through regulating metabolism and ferroptosis. However, p53 is always lost or mutated in human and the loss or mutation of p53 is related to a high risk of tumors. Although the link between p53 and cancer has been well established, how the different p53 status of tumor cells help themselves evade immune response remains largely elusive. Understanding the molecular mechanisms of different status of p53 and tumor immune evasion can help optimize the currently used therapies. In this context, we discussed the how the antigen presentation and tumor antigen expression mode altered and described how the tumor cells shape a suppressive tumor immune microenvironment to facilitate its proliferation and metastasis.

Collagen-based scaffolds lack mechanical strength, flexibility, and tunable pore structure, affecting tissue repair outcomes and restricting their wide clinical application. Here, two kinds of scaffolds were prepared by a combination of vacuum homogenization, natural air drying, water soaking, lyophilization, and crosslinking. Compared with the scaffolds made of collagen molecules (Col-M), the scaffolds made of collagen aggregates (Col-A) exhibited higher mechanical strength (ultimate tensile strength: 1.38 ​± ​0.26 ​MPa vs 15.46 ​± ​1.55 ​MPa), stronger flexibility, advanced cell adhesion, survival, and proliferation. Subcutaneous implantation in rats showed that Col-A scaffolds promoted cell infiltration, macrophage polarization, and vascularization. Furthermore, the Col-A scaffolds inhibited abdominal bulges due to their adequate mechanical support, and they also promoted vascularized muscle regeneration in a rat abdominal hernia defect model. Our study provides a novel strategy for generating high-strength, flexible, porous collagen-based scaffolds, which can be applied to tissue repair with mechanical strength requirements. It broadens their application range in the field of regenerative medicine.

Accurate traffic speed forecasting not only can help traffic management departments make better judgments and improve the efficacy of road monitoring but also can help drivers plan their driving routes and arrive safely and smoothly at their destination. This paper focuses on the lack of traffic speed data and proposes a method for traffic speed forecasting based on the multitemporal traffic flow volume of the previous and later moment states. First, according to traffic flow volume data, the different traffic patterns of previous and later moment states were extracted. Second, the performance of five forecasting models, namely, long short-term memory (LSTM), backpropagation (BP), classification and regression trees, k-nearest neighbor, and support vector regression, were compared. Finally, the model with the best prediction results was used to conduct sensitivity analysis experiments for different traffic patterns. Through a real-data case study, we found that the LSTM model has the highest prediction accuracy compared to other models in both time and space. This traffic pattern “previous = 3 and later = 3” can forecast traffic speed more accurately, and its forecasting ability is robust across a range of scenarios.

Background Men who have sex with men (MSM), a population bearing the greatest HIV burden in many countries, may also be vulnerable to COVID-19. COVID-19 vaccines are essential to containing the pandemic. However, vaccine hesitancy may compromise vaccine coverage. We aimed to understand the uptake of COVID-19 vaccine and factors associated with COVID-19 vaccine hesitancy among HIV-infected MSM in mainland China. Methods A cross-sectional online survey among HIV-infected MSM was conducted between 13 and 21 February 2021 in mainland China. Variables including demographics, mental health status, HIV characteristics, and knowledge of and attitudes toward COVID-19 pandemic and COVID-19 vaccine were collected. Chi-square tests and multivariable logistic regression were used to analyze factors associated with COVID-19 vaccine hesitancy. Results A total of 1295 participants were included. The median age was 29.3 years (interquartile range [IQR] 25.2–34.0 years). The uptake of COVID-19 vaccine was 8.7%. Two main reasons for receiving vaccines were “regarded vaccination as self-health protection” (67.3%) and “trust in domestic medical technology” (67.3%). Among participants who did not initiate vaccination, concern about side effects (46.4%) and disclosure of HIV infection (38.6%) were top two reasons, and 47.2% had higher vaccine hesitancy. Men who had with high antiretroviral therapy (ART) adherence (adjusted odds ratio [aOR] 0.53, 95% confidence interval [CI] 0.35–0.80), often (0.26, 0.17–0.40) or sometimes (0.46, 0.31–0.67) paid attention to information about the COVID-19 vaccine, preferred domestic vaccines (0.37, 0.24–0.59), thought the pandemic had moderate (0.58, 0.38–0.90) and moderately severe or severe impact (0.54, 0.38–0.78) on immunity, who were waiting for vaccination programs organized at workplace (0.60, 0.44–0.81) and who were unaware of where to get COVID-19 vaccine (0.61, 0.45–0.82) had lower degree of COVID-19 vaccine hesitancy. Men who were concerned about the efficacy (1.72, 1.16–2.54) and side effects (2.44, 1.78–3.35) had higher degree of COVID-19 vaccine hesitancy. Conclusion COVID-19 vaccine uptake among HIV-infected MSM is still suboptimal. Understanding influencing factors of vaccine hesitancy among this group and making tailored measures to alleviate hesitancy would help improve the coverage of COVID-19 vaccination in this population.

Abstract Cell-free fetal DNA fraction (FF) in maternal plasma is a key parameter affecting the performance of noninvasive prenatal testing (NIPT). Accurate quantitation of FF plays a pivotal role in these tests. However, there are few methods that could determine FF with high accuracy using shallow‐depth whole‐genome sequencing data. In this study, we hypothesized that the actual FF in maternal plasma should be proportional to the discrepancy rate between the observed genotypes and inferred genotypes based on the linkage disequilibrium rule in certain polymorphism sites. Based on this hypothesis, we developed a method named Linkage Disequilibrium information-based cell-free Fetal DNA Fraction (LDFF) to accurately quantify FF in maternal plasma. This method achieves a high performance and outperforms existing methods in the fetal DNA fraction estimation. As LDFF is a gender-independent method and developed on shallow-depth samples, it can be easily incorporated into routine NIPT test and may enhance the current NIPT performance.

ObjectiveAlthough phthalates are common environmental pollutants, few studies have focused on the relationship of phthalates exposure with non-alcoholic fatty liver disease (NAFLD) or liver fibrosis, and especially, the alternative phthalates have been questioned in recent years about whether they are better choices. Thus, this study aimed to explore the associations of exposure to major phthalates or alternative phthalates with NAFLD and liver fibrosis.MethodsData of 1450 adults from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 were collected. The urinary metabolite concentrations of di-2-ethylhexyl phthalate (DEHP), diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP) were detected. Controlled attenuation parameter (CAP) and median liver stiffness measurement (LSM) were acquired for quantitative diagnosis of NAFLD and liver fibrosis by vibration-controlled transient elastography. Multivariate logistic regression analysis and linear regression analysis were performed to examine the associations between phthalates and NAFLD and liver fibrosis.ResultsAfter adjustment of the potential factors, the prevalence of NAFLD was significantly elevated among those in the fourth quartile of mono-(2-ethyl-5-carboxypentyl) phthalate (OR, 95%CI = 2.719, 1.296, 5.700, P = 0.016), mono (2-ethyl-5-hydroxyhexyl) phthalate (OR, 95%CI = 2.073, 1.111, 3.867, P = 0.037). No significant association was found between the alternative phthalates and NAFLD. The similar result was gained by linear regression analysis that MECPP was still significantly associated with Ln CAP (Q4 vs. Q1: β, 95%CI = 0.067, 0.017, 0.118, P = 0.027). After adjustment for the same covariates, no significant association between phthalates and liver fibrosis was found in logistics regression analysis.ConclusionsAll in all, higher prevalence of NAFLD is correlated with DEHP but not DINP or DIDP in American adults. There is no significant relationship between phthalates and liver fibrosis defined as LSM ≥ 8 Kpa. Nevertheless, further research is needed to provide evidence of causality.

The immune system is highly networked and complex, which is continuously changing as encountering old and new pathogens. However, reductionism-based researches do not give a systematic understanding of the molecular mechanism of the immune response and viral pathogenesis. Here, we present HUMPPI-2022, a high-quality human protein-protein interaction (PPI) network, containing > 11,000 protein-coding genes with > 78,000 interactions. The network topology and functional characteristics analyses of the immune-related genes (IRGs) reveal that IRGs are mostly located in the center of the network and link genes of diverse biological processes, which may reflect the gene pleiotropy phenomenon. Moreover, the virus-human interactions reveal that pan-viral targets are mostly hubs, located in the center of the network and enriched in fundamental biological processes, but not for coronavirus. Finally, gene age effect was analyzed from the view of the host network for IRGs and virally-targeted genes (VTGs) during evolution, with IRGs gradually became hubs and integrated into host network through bridging functionally differentiated modules. Briefly, HUMPPI-2022 serves as a valuable resource for gaining a better understanding of the composition and evolution of human immune system, as well as the pathogenesis of viruses.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a broad clinical spectrum of coronavirus disease 2019 (COVID-19). The development of COVID-19 may be the result of a complex interaction between the microbial, environmental, and host genetic components. To reveal genetic determinants of susceptibility to COVID-19 severity in the Chinese population, we performed a genome-wide association study on 885 severe or critical COVID-19 patients (cases) and 546 mild or moderate patients (controls) from two hospitals, Huoshenshan and Union hospitals at Wuhan city in China. We identified two loci on chromosome 11q23.3 and 11q14.2, which are significantly associated with the COVID-19 severity in the meta-analyses of the two cohorts (index rs1712779: odds ratio [OR] = 0.49; 95% confidence interval [CI], 0.38–0.63 for T allele; P = 1.38 × 10−8; and index rs10831496: OR = 1.66; 95% CI, 1.38–1.98 for A allele; P = 4.04 × 10−8, respectively). The results for rs1712779 were validated in other two small COVID-19 cohorts in the Asian populations (P = 0.029 and 0.031, respectively). Furthermore, we identified significant eQTL associations for REXO2, C11orf71, NNMT, and CADM1 at 11q23.3, and CTSC at 11q14.2, respectively. In conclusion, our findings highlight two loci at 11q23.3 and 11q14.2 conferring susceptibility to the severity of COVID-19, which might provide novel insights into the pathogenesis and clinical treatment of this disease.

Chaolong Wang and colleagues report a large genome-wide association study for COVID-19 severity in Chinese individuals. By meta-analysis with European data, they identify 3 loci associated with severe disease that suggest key roles for the adaptive immune system and the ABO blood group system in development of severe COVID-19.