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Abstract Acute-on-chronic liver failure (ACLF) is a syndrome characterized by the acute decompensation of chronic liver disease, resulting in organ failure and high short-term mortality. The progression of ACLF is dynamic and reversible in a considerable proportion of patients during hospitalization. Early detection and accurate assessment of ACLF are essential; however, ideal methods for this purpose are still lacking. Therefore, this study aimed to develop a new score for predicting the onset of ACLF in patients with various chronic liver diseases.A total of 6,188 patients with various chronic liver diseases were included in the study. Clinical and laboratory data were collected, and the occurrence of ACLF within 28 days was recorded. The Lasso-Cox regression method was employed to develop prediction models for the onset of ACLF at 7, 14, and 28 days. Among 5,221 patients without ACLF, 477 progressed to ACLF within 28 days. Seven predictors were identified as significantly associated with the occurrence of ACLF at 7, 14, and 28 days. A new scoring system was developed as follows: [NEUT ≥ 7, 109/L; 1 or 0] × 0.49 + [PLT 7, mmol/L; 1 or 0] × 0.51 + Ln[INR] × 0.87 + 3.40. This new score demonstrated superior discrimination, with the C-indexes of 0.958, 0.944, and 0.938 at 7, 14, and 28 days, respectively, outperforming those of four other scores (CLIF-C-ACLF-Ds, MELD, MELD-Na, and CLIF-C-ADs score; all P

Abstract Background The activation of the DNA damage response (DDR) heavily relies on post-translational modifications (PTMs) of proteins, which play a crucial role in the prevention of genetic instability and tumorigenesis. Among these PTMs, palmitoylation is a highly conserved process that is dysregulated in numerous cancer types. However, its direct involvement in the DDR and the underlying mechanisms remain unclear. Methods CRISPR-Cas9 technology was used to generate the PORCN KO and PORCN NLS KO cell lines. The effects of PORCN NLS in the DDR were verified by colony formation assays, MTT assays, the DR/EJ5 homologous recombination/non-homologous end-joining reporter system, xenograft tumor growth and immunofluorescence. Mechanisms were explored by mass spectrometry, acyl-biotin exchange (ABE) palmitoylation assay, Click-iT assay, cell subcellular fractionation assay, Western blot analysis, and in vivo and in vitro co-immunoprecipitation. Results In this study, we introduce evidence that Porcupine (PORCN) is an integral component of and plays a critical role in the DDR. PORCN deficiency hampers nonhomologous end joining (NHEJ) and highly sensitizes cells to ionizing radiation (IR) both in vitro and in vivo. We also provide evidence that PORCN possesses a nuclear fraction (nPORCN) with S-acyltransferase activity, unlike its membrane-bound O-acyltransferase in the endoplasmic reticulum. Furthermore, we show that nPORCN is necessary for the successful activation of NHEJ. Using mass spectrometry, we reveal the existence of an nPORCN complex and show that nPORCN mediates the S-palmitoylation of XRCC6/Ku70 at five specific cysteine sites in response to IR. Mutation of these sites causes a substantial increase in radiosensitivity and delays NHEJ. Additionally, we present evidence that nPORCN-dependent Ku70 palmitoylation is required for DNA-PKcs/Ku70/Ku80 complex formation. Conclusion Our findings underscore the crucial role of nPORCN-dependent Ku70 S-palmitoylation in the DDR.

Abstract Background and aims Diabetic peripheral neuropathy (DPN) and diabetic nephropathy (DN) both have microcirculation dysfunction. Urinary albumin-to-creatinine ratio (UACR) is a biomarker for DN. We aimed to explore the links between DPN and UACR in patients with type 2 diabetes mellitus (T2DM). Methods A total of 195 T2DM patients were defined as Control or DPN group. Clinical parameters were compared, and the association between HbA1c (or UACR) and DPN was analyzed. Risk factors for DPN were observed, and the diagnostic values of HbA1c and UACR were assessed. Results Compared with 104 participants without DPN, 91 individuals with DPN exhibited higher HbA1c and UACR levels. In all patients, increased HbA1c and UACR were identified as risk factors for DPN in individuals with T2DM. Moreover, increased HbA1c was a risk factor for DPN in volunteers without DN, whereas elevated UACR was determined as a risk factor for DPN in participants with DN. The cut-off point for HbA1c (7.65%) in patients without DN had a sensitivity of 86.0% and specificity of 44.6%, while the cut-off point for UACR (196.081 mg/g) in patients with DN had a sensitivity of 52.9% and specificity of 76.2%. Conclusion Elevated HbA1c and UACR levels are risk factors for DPN and may serve as potential biomarkers for DPN in T2DM patients.

Abstract A 40-year-old male with EML4-ALK (E6:A20) fusion variant 3 and previously unreported PLEKHA7-ALK (P3:A20) fusion in lung adenocarcinoma exhibited resistance to alectinib and chemotherapy. Subsequent next-generation sequencing (NGS) from the plasma specimen revealed the co-existing mutation in the KEAP1 gene, which may represent an intrinsic resistance to ALK-TKI. Furthermore, the presence of double fusion PLEKHA7-ALK (P3:A20) may also have played a critical role in the resistance to alectinib. KEAP1 mutation (p.E244K) was also founded in this patient which may lead to resistance to standard chemotherapy. The patient was then treated with brigatinib, which effectively halted the rapid progression. Unfortunately, the patient deceased to uncontrollable, rapidly progressing pleural effusion and pulmonary embolism, resulting in an overall survival of 9 months. This represents the rare case of NSCLC with a double fusion of EML4-ALK and PLEKHA7-ALK, exhibiting resistance to alectinib and chemotherapy. Our case suggests that the double fusion of EML4-ALK and PLEKHA7-ALK and co-existing KEAP1 mutation may serve as an adverse prognostic factor. Additionally, brigatinib may offer a potential treatment option for lung adenocarcinoma patients with PLEKHA7-ALK (P3:A20) fusion.

Deep coal mining, in addition to facing the three “high” and one “disturbance”, faces a high-stress corrosion environment formed by underground corrosive atmosphere, high stress, strong disturbance, and other factors. Taking the deep mines in the Juye Coalfield, Shandong, as the engineering background, the high-stress corrosion characteristics and influencing factors of deep mining are analyzed. Experimental and theoretical research is conducted on the anchor rod material to reveal the degradation mechanism of anchor rod strength under high-stress corrosion environment, and a theoretical model for the degradation of rod strength is derived. The results are as follows: ① through the SEM, corrosion SSRT, and accelerated corrosion experiments on rod materials, it is found that the corrosion causes a decrease in the elongation at break and fracture time of rod materials by 8.22% and 8.34%, respectively, compared to inert conditions. With the increase of corrosion rate, the material failure mode transitions from ductile to brittle fracture, and the localized corrosion type gradually evolves from pitting to uniform corrosion. ② Combining experimental results with electrochemical theory and non-uniform corrosion models, introducing the Pruckenr temperature influence factor, a time-varying model for the degradation of rod material strength is derived. The in-depth investigation of the impact of service environment temperature T, rod cross-sectional radius R, and material room temperature corrosion rate Vh,298K on the service life of the rod reveals that R is linearly positively correlated with service life. The relationship between T and Vh,298K with service life shows that the degree of service life decay decreases as the levels of influencing factors increase. ③ Combining experimental results with the energy absorption principle of anchor rods, the limit energy absorption capacity of roadway anchor rod support is calculated and analyzed. The results show that as the corrosion rate of the anchor rod increases, the energy absorption of the anchor rod decreases, the maximum seismic resistance decreases, and the risk of roadway dynamic instability disasters increases.

Abstract In this work, numerous rogue wave solution strategy (MRWSS) agreeing to the Hirota bilinear hypothesis is utilized. The said strategy to build different soliton wave solutions for the generalized Hirota-Satsuma-Ito (GHSI) condition is considered. These numerous soliton wave solutions incorporate first-order, second-order, third-order, and fourth-order waves solutions and so on, which are all depending on the starting theory of chosen capacities. For the lump solution with one most extreme or least esteem, the properties of the Hessian lattice are examined. Besides, the arrangements are contained the lump-two kink arrangements, cross-kink wave arrangements, periodic wave arrangements, and periodic-kink wave arrangements. The various classes of arrangements are gotten. We make utilize of the direct superposition procedure to find out N-soliton wave arrangements to the said condition. The appropriateness and viability of the obtained arrangements is detailed through the reenactment comes about within the shape of 3-D, density, and 2-D charts. The gotten comes about in this work are anticipated to open modern viewpoints for the traveling wave theory.

Abstract Aims Night blindness (NB), an important manifestation of VA deficiency, may be associated with the odds of diabetes. The aim of this study was to explore the probable association between NB history and diabetes in Chinese community-dwelling adults. Methods This multi-center, cross-sectional study enrolled a total of 5664 participants aged 18–82 years from eight sites in China. Information on demographics and medical history was collected using a standardized questionnaire. Diabetes was diagnosed based on the oral glucose tolerance test or a self-reported history. NB history was ascertained by a face-to-face interview with reference to the recommendation by the World Health Organization. Logistic regression analysis was used to evaluate the association between NB history and the odds of diabetes. Results A total of 5049 participants were finally included, with 252 ascertained with NB history and 1076 with diabetes. The mean age of included participants was 52.9 years, and the percentage of participants with NB history was significantly higher in participants with diabetes than those without (7.0% vs. 4.5%). The multivariable adjusted odds ratio for diabetes was 1.41 (95% confidence interval 1.06, 1.89) in participants with NB history compared with those without. Furthermore, mediation analysis showed that obesity, as assessed by waist-height ratio, partially mediated the relationship between NB history and increased odds of diabetes. Conclusions The results suggest that NB history might be associated with increased odds of diabetes in Chinese community-dwelling adults.

Abstract Of the hitherto over 60 taxonomically identified species in the genus of Pseudo-nitzschia, 26 have been confirmed to be toxigenic. Nevertheless, the acquisition and evolution of the toxin biosynthesis (dab) genes by this extensive group of Pseudo-nitzschia species remains unclear. Through constructing chromosome-level genomes of three Pseudo-nitzschia species and draft genomes of ten additional Pseudo-nitzschia species, putative genomic integration sites for the dab genes in Pseudo-nitzschia species were explored. A putative breakpoint was observed in syntenic regions in the dab gene cluster-lacking Pseudo-nitzschia species, suggesting potential independent losses of dab genes. The breakpoints between this pair of conserved genes were also identified in some dab genes-possessing Pseudo-nitzschia species, suggesting that the dab gene clusters transposed to other loci after the initial integration. A “single acquisition, multiple independent losses (SAMIL)” model is proposed to explain the acquisition and evolution of the dab gene cluster in Pseudo-nitzschia species.

The direct one-step separation of polymer-grade C2H4 from complex light hydrocarbon mixtures has high industrial significance but is very challenging. Herein, an ethylene-adsorption-weakening strategy is applied for precise regulation of the pore geometry of four tailor-made metal–organic frameworks (MOFs) with pillar-layered structures, dubbed TYUT-10/11/12/13. Based on its pore geometry design and functional group regulation, TYUT-12 exhibits exceptional selective adsorption selectivity toward C3H8, C3H6, C2H6, C2H2, and CO2 over C2H4; its C2H6/C2H4 adsorption selectivity reaches 4.56, surpassing the record value of 4.4 by Fe2(O2)(dobdc) (dobdc4− = 2,5-dioxido-1,4-benzenedicarboxylate). The weak π–π stacking binding affinity toward C2H4 in TYUT-12 is clearly demonstrated through a combination of neutron powder diffraction measurements and theoretical calculations. Breakthrough experiments demonstrate that C2H4 can be directly obtained from binary, ternary, quaternary, and six-component light hydrocarbon mixtures with over 99.95% purity.

Objective: To clarify the specific mechanisms of action of raw Phellodendron chinense Schneid. (RPC) and saltwater-processed PC (SPC) in the treatment of rats with a kidney-yin deficiency pattern (KYDP). Methods: Healthy rats were administered hydrocortisone to establish a KYDP model. The rats were divided into seven groups: blank control, model, positive control (Liuwei Dihuang pills), high-dose RPC, low-dose RPC, high-dose SPC, and low-dose SPC. Enzyme-linked immunosorbent assay was used to measure the levels of cAMP, cGMP, TRH, TSH, T3, T4, IFN-γ, TNF-α, and testosterone in the serum and the levels of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in the liver. TRH mRNA expression in the rat hypothalamus was measured using RT-PCR. THRα1+2 protein expression in the hypothalamus of rats was measured using Western blot. Immunohistochemistry was performed to determine the expression levels of FAS, FasL, and TSHR. Flow cytometry was used to determine CD4+ and CD8+ T lymphocyte levels. Illumina MiSeq sequencing technology was used to evaluate the diversity of intestinal flora in KYDP rats. Results: The cAMP/cGMP ratio was significantly higher in the model group than in the blank control group (P = .048). Compared with the model group, after administration, the levels of the above-mentioned serum and liver indexes decreased, except that of testosterone. The CD4+/CD8+ ratio also decreased. Compared with the RPC group, the levels of T3, IFN-γ, FAS, FasL, and TSHR in the SPC group decreased whereas that of testosterone increased. Additionally, immune function and intestinal flora diversity improved in the SPC group. SPC proved to be more effective in improving liver energy metabolism in KYDP rats than RPC. Conclusion: SPC had a better therapeutic effect on KYDP than RPC. The underlying mechanism of action may be related to improvements in liver energy metabolism, immune function, and intestinal flora diversity.

Abstract Background The prevalence of possible sarcopenia is notably high among maintenance hemodialysis (MHD) patients. Possible sarcopenia, defined as a decrease in muscle strength and/or somatic function, is an early and reversible condition between non-sarcopenic and sarcopenia, and early recognition and intervention for possible sarcopenia is important for preventing adverse outcomes and improving the quality of life of these patients. This study aimed to establish a simple and effective model for screening and identifying MHD patients at high risk of possible sarcopenia by using 50 kHz-Whole Body Phase Angle (PhA), with a specific focus on gender differences. Methods This prospective cross-sectional study was conducted from September to December 2023 at the Wenjiang Hemodialysis Center in the Department of Nephrology, West China Hospital, Sichuan University, Chengdu, China. A total of 244 MHD patients, including 130 males and 114 females, were enrolled. Data were collected prospectively, including demographic information and physical measurements. All participants provided informed consent before enrollment. Measurements were taken post-dialysis to ensure consistency. The whole-body phase angle was measured using the InBody S10 device, grip strength was measured using an electronic grip strength tester, and physical function was assessed by the Short Physical Performance Battery (SPPB). The Skeletal Muscle Index (SMI) was also calculated. Results A total of 244 patients receiving hemodialysis were enrolled in this study. Among these, 109 patients were categorized as non-sarcopenic, 111 as having possible sarcopenia, and 24 as sarcopenic. The prevalence of sarcopenia among MHD patients is 9.8%, while the prevalence of possible sarcopenia is 45.5%. The receiver operating characteristic (ROC) curve analysis showed that for male patients, the AUC of PhA for predicting possible sarcopenia was 0.798, with a sensitivity of 80.36%, specificity of 69.70%, and a cutoff value of 6.20°. For female patients, the AUC of PhA was 0.701, with a sensitivity of 70.91% and specificity of 62.79%, and a cutoff value of 5.70°. Conclusions PhA may be a useful and simple predictor of the risk of possible sarcopenia in MHD patients, and more research is needed to further promote the use of PhA in possible sarcopenia.

Abstract The neutrophil-to-lymphocyte ratio (NLR), a simple marker of systemic inflammation, is crucial in the progression of cardiovascular diseases (CVD). Its predictive value for all-cause and cardiovascular mortality in CVD patients with diabetes or pre-diabetes remains unclear. We analyzed 3,780 CVD patients with diabetes or pre-diabetes from the National Health and Nutrition Examination Survey (2001–2018). Kaplan-Meier survival curves, weighted Cox proportional hazards models, and restricted cubic spline (RCS) analyses were used to assess the relationship between NLR and mortality risk. RCS revealed a U-shaped association between NLR and all-cause mortality, with an inflection point at 1.776. For NLR

Abstract Background Chronic overlapping pain conditions (COPCs), pain-related conditions that frequently occur together, may occur in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and could impact illness severity. This study aimed to identify comorbid COPCs in patients with ME/CFS and evaluate their impact on illness severity. Methods We used data from 923 participants in the Multi-Site Clinical Assessment of ME/CFS study, conducted in seven U.S. specialty clinics between 2012 and 2020, who completed the baseline assessment (595 ME/CFS and 328 healthy controls (HC)). COPCs included chronic low back pain (cLBP), chronic migraine/headache (cMHA), fibromyalgia (FM), interstitial cystitis/irritable bladder (IC/IB), irritable bowel syndrome (IBS), temporomandibular disorder (TMD). Illness severity was assessed through questionnaires measuring symptoms and functioning. Multivariate analysis of variance and analysis of covariance models were used for analyses. Log-binomial regression analyses were used to compute prevalence of COPCs and prevalence ratios (PR) between groups with 95% confidence intervals. Both unadjusted and adjusted results with age and sex are presented. Results 76% of participants with ME/CFS had at least one COPCs compared to 17.4% of HC. Among ME/CFS participants, cMHA was most prevalent (48.1%), followed by FM (45.0%), cLBP (33.1%), and IBS (31.6%). All individual COPCs, except TMD, were significantly more frequent in females than males. The unadjusted PR (ME/CFS compared to HC) was highest for FM [147.74 (95% confidence interval (CI) = 20.83-1047.75], followed by cLBP [39.45 (12.73-122.27)], and IC/IB [13.78 (1.88-101.24)]. The significance and order did not change after age and sex adjustment. The COPC comorbidities of cLBP and FM each had a significant impact on most health measures, particularly in pain attributes (Cohen’s d effect size 0.8 or larger). While the impact of COPC comorbidities on non-pain attributes and quality of life measures was less pronounced than that on pain, statistically significant differences between ME/CFS participants with and without COPCs were still evident. Conclusions More than 75% of ME/CFS participants had one or more COPCs. Multiple COPCs further exacerbated illness severity, especially among females with ME/CFS. Assessment and management of COPCs may help improve the health and quality of life for patients with ME/CFS.

Abstract Controlling drug release rate and providing physical and chemical stability to the active pharmaceutical ingredient are key properties of oral solid dosage forms. Here, we demonstrate a formulation strategy using phase-separated polymer blends where the morphology provides a route for tuning the drug release profile. By utilising phase separation of a hydrophobic and a hydrophilic polymer, the hydrophilic component will act as a channelling agent, creating a porous network upon dissolution that will dictate the release characteristics. With ptychographic X-ray tomography and scanning transmission X-ray microscopy we reveal how the morphology depends on both polymer fraction and presence of drug, and how the drug is distributed over the polymer domains. Combining X-ray imaging results with dissolution studies reveal how the morphologies are correlated with the drug release and showcase how tuning the morphology of a polymer matrix in oral formulations can be utilised as a method for controlled drug release.

Abstract Excessive glucocorticoid (GC) action is linked to various metabolic disorders. Recent findings suggest that disrupting skeletal GC signaling prevents bone loss and alleviates metabolic disorders in high-fat diet (HFD)-fed obese mice, underpinning the neglected contribution of skeletal GC action to obesity and related bone loss. Here, we show that the elevated expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), the enzyme driving local GC activation, and GC signaling in osteoblasts, are associated with bone loss and obesity in HFD-fed male mice. Osteoblast-specific 11β-HSD1 knockout male mice exhibit resistance to HFD-induced bone loss and metabolic disorders. Mechanistically, elevated 11β-HSD1 restrains glucose uptake and osteogenic activity in osteoblast. Pharmacologically inhibiting osteoblastic 11β-HSD1 by using bone-targeted 11β-HSD1 inhibitor markedly promotes bone formation, ameliorates glucose handling and mitigated obesity in HFD-fed male mice. Taken together, our study demonstrates that osteoblastic 11β-HSD1 directly contributes to HFD-induced bone loss, glucose handling impairment and obesity.

Abstract Objectives Post-myocardial infarction ventricular septal rupture (PIVSR) is one of the most severe types of mechanical complications after acute myocardial infarction (AMI) with high mortality and poor prognosis. The risk factors for short-term mortality of patients with PIVSR may be not widely recognized. We aimed to assess the prevalence and short-term mortality risk predictors of PIVSR. Methods A total of 62 patients with a diagnosis of PIVSR were admitted to three top general public hospitals in Chongqing, China. Clinical characteristics and short-term outcomes of patients with PIVSR were compared. Predictors of PIVSR were assessed using logistic regression analysis. Results Mean age was 70.7 ± 10.7 years (38.7% female). The overall in-hospital mortality of PIVSR remained high (71%). Most (47/62) of the patients were in Killip class III or IV at the time of rupture diagnosis. Logistic regression analysis revealed that white blood cell count (WBC, OR 1.619, 95% CI 1.172–2.237, P = 0.005), cardiogenic shock (OR 47.706, 95%CI 2.859-795.945, P = 0.007) and left ventricular ejection fraction (LVEF, OR 0.803, 95%CI 0.689–0.936, P = 0.009) were independent risk factors of in-hospital early mortality. The nomogram developed for predicting the risk of short-term mortality showed a robust discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.956 (95%CI 0.912-1.000). Conclusion The short-term mortality of PIVSR remained high. WBC, cardiogenic shock, and LVEF were the independent predictive factors of short-term mortality. Our nomogram might be used to predict early mortality of patients with PIVSR.

Abstract Background The triglyceride–glucose (TyG) index has demonstrated correlations with adverse clinical outcomes in patients with ischaemic stroke, coronary heart disease and cardiac failure. However, its association with overall mortality in individuals concurrently experiencing heart failure (HF) and chronic kidney disease (CKD) remains inadequately explored. Methods Utilizing the Medical Information Mart for Intensive Care IV (Version 2.2) repository, subjects underwent quartile stratification based on the TyG index. The primary endpoint was all‐cause mortality during hospitalization. Cox proportional hazard models were employed to examine the correlation between TyG and all‐cause mortality in HF patients with CKD. Evaluation involved Kaplan–Meier (KM) analysis and restricted cubic splines (RCSs) to compare mortality rates during hospitalization and 1 year after admission across cohorts with varying TyG index levels. Results A cohort of 1537 HF and CKD patients participated. Cox regression analysis revealed elevated TyG levels as an independent risk factor for both in‐hospital and 1 year mortality. RCS analysis indicated a rising, non‐linear association between TyG levels and all‐cause mortality (P value for non‐linear

Background: To evaluate the effectiveness and safety of the Shenfu injection (SFI) combined with standard bundle treatment in septic patients with hypoperfusion. Method: This study was a multi-center, randomized, open-label, controlled trial conducted in four teaching hospitals in China. The septic patients with hypoperfusion and traditional Chinese medicine (TCM) syndrome with Yang-Qi deficiency were enrolled from January 2019, through September 2020. Eligible patients were randomly allocated in a 1:1 ratio to either receive 60 mL of SFI infusion per day plus standard treatment (SFI group) or standard bundle treatment alone (control group). The primary outcome was 28-day all-cause mortality. Secondary outcomes were 90-day all-cause mortality time to weaning from mechanical ventilation, time to weaning from vasopressors, time to discharge from the ICU and hospital, and laboratory results after randomization. Results: A total of 188 patients completed the trail. This study revealed that the results of the SFI group and the control groups were not statistically significant in 28-day all-cause mortality (10.6% vs. 20.2%, respectively; P=0.106). The infusion of SFI was associated with a significant reduction in the duration of vasopressor use (median=4.0 days, interquartile range [IQR]: 2.0 days–6.0 days vs. median=5.0 days, IQR: 3.0 days–8.0 days, respectively; P=0.043). Patients in the SFI group had statistically greater reductions in plasma lactate levels compared with those in the control group at the first 12 h (median=1.1 mmol/L, IQR: 0.3–2.0 mmol/L vs. median=0.0 mmol/L, IQR: −0.2 to 0.8 mmol/L, respectively; P

Motivated by the electric vehicle revolution, the demand for lithium (Li) has significantly increased during the last decade. Li is the key strategic resource in energy structure transformation to be extensively employed in several fields, such as new energy vehicles, electronic products, and energy storage. For sustainable Li supply, developing cost-effective and green methods to extract Li from various sources is urgently needed. Due to the abundant reserves and low cost, the recovery of Li from salt-lake brines has garnered immense attention globally. China is rich in salt-lake resources; among them, brine Li resources are mainly distributed in Qinghai and Xizang, but the separation is difficult because of low concentration and high Mg/Li ratio. Moreover, the composition of salt lakes in different regions varies, and the poor technical universality restricts the development of Li extraction from salt lakes in China. This review summarizes the major developments in Li recovery from brines. An overview of the Li distribution, endowment characteristics, extraction methods, and development direction is presented, concentrating on the mechanisms, operation and development of precipitation, solvent extraction, adsorption, membrane separation, and electrochemical Li extraction. The advantages and disadvantages, separation effects, and applicable conditions of the extraction methods are examined. Although the prevalent precipitation, extraction, and adsorption methods are appropriate for the mass extraction of Li from brine sources with low Mg/Li ratios, they are not ecofriendly and typically show low Li recovery. For example, precipitation and extraction methods have issues with large dosages of chemicals and severe environmental effects; meanwhile, adsorption methods have drawbacks of intensive water use and easy dissolution of adsorbents, greatly limiting industrial application. The emerging membrane separation and electrochemical methods have good separation effects, limited requirements for additional chemicals, minimal waste production, wide applicability, and outstanding performance in Mg/Li or Na/Li separation, thereby demonstrating broad application prospects. However, these methods are limited by the poor technical maturity for large-scale lithium recovery. We underscore the most pressing challenges that these technologies encounter, including limited electrode capacity, poor electrode stability, and limited Li selectivity between homovalent ions. Then, potentially effective strategies are systematically described to overcome these challenges. Finally, future development directions and research focus on Li extraction technology from salt-lake brines are prospected.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease caused by abnormal expression of glycosylphosphatidylinositol (GPI) on the cell membrane due to mutations in the phosphatidylinositol glycan class A(PIGA) gene. It is commonly characterized by intravascular hemolysis, repeated thrombosis, and bone marrow failure, as well as multiple systemic involvement symptoms such as renal dysfunction, pulmonary hypertension, swallowing difficulties, chest pain, abdominal pain, and erectile dysfunction. Due to the rarity of PNH and its strong heterogeneity in clinical manifestations, multidisciplinary collaboration is often required for diagnosis and treatment. Peking Union Medical College Hospital, relying on the rare disease diagnosis and treatment platform, has invited multidisciplinary clinical experts to form a unified opinion on the diagnosis and treatment of PNH, and formulated the Expert Consensus of Multidisciplinary Diagnosis and Treatment for Paroxysmal Nocturnal Hemoglobinuria (2024), with the hope of promoting the standardization of PNH diagnosis and treatment.

As a core component in the industrial sector， the efficient and high-precision forming of hollow shafts is crucial for ensuring product performance and improving production efficiency. However， traditional open die forging and closed die forging methods face significant challenges， such as low material utilization， insufficient forming precision， and limited production efficiency. These issues severely restrict the development and application of hollow shafts. This paper reviews the latest research advancements in hollow shaft manufacturing， analyzes the current technical challenges， and explores the prospects of emerging forming technologies as well as the application of digital and intelligent technologies in this field. The paper summarizes the applications and advantages of various technologies， including rotary forging， squeeze casting， wedge cross rolling， and three-roll skew rolling， in enhancing the manufacturing efficiency and forming precision of hollow shafts. Rotary forging， by rotating and forging the material， effectively improves material utilization and product performance. Squeeze casting achieves high precision and consistency by pressing liquid metal into molds under high pressure. Wedge cross rolling drives the billet through the mold for reverse rotation， causing radial compression and axial elongation deformation of the metal， ultimately forming the desired stepped shaft parts， thereby improving dimensional accuracy and production efficiency. Three-roll skew rolling technology optimizes the loading mechanism to achieve efficient and continuous axial plastic forming through localized loading. With the manufacturing industry moving towards digitalization and intelligence， hollow shaft manufacturing technology is expected to achieve significant advancements and breakthroughs in the future.

Abstract Immunotherapy has shown marked progress in promoting systemic anti-colorectal cancer (CRC) clinical effects. For further effectively sensitizing CRC to immunotherapy, we have engineered a pH-sensitive zeolitic imidazolate framework-8 (CS/NPs), capable of efficient cGAS-STING pathway activation and immune checkpoint blockade, by encapsulating the chemotherapeutic mitoxantrone (MTX) and immunomodulator thymus pentapeptide (TP5) and tailoring with tumor-targeting chondroitin sulfate (CS). In this nanoframework, CS endows CS/NPs with specific tumor-targeting activity and reduced systemic toxicity. Of note, the coordinated Zn2+ disrupts glycolytic processes and downregulates the expression of glucose transporter type 1 (GLUT1), thus depriving the cancer cells of their energy. Zn2+ further initiates the adenosine 5’-monophosphate activated protein kinase (AMPK) pathway, which leads to PD-L1 protein degradation and sensitizes CRC cells to immunotherapy. Moreover, the damaged double-stranded DNA during MTX treatment activates the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, which works together with TP5 induced the proliferation and differentiation of T lymphocytes and dendritic cells to further enhance the anti-CRC immune response. Therefore, CS/NPs efficiently sensitize cells to chemotherapy and stimulate systemic antitumor immune responses both in vitro and in vivo, representing a promising strategy to increase the feasibility of CRC immunotherapy. Graphical Abstract

Rural transformation development (RTD) is crucial for achieving sustainable development in poverty-stricken rural areas. The Garze-Ngawa-Liangshan (GNL) region, an impoverished minority area in Southwest China, has undergone significant RTD in recent decades. This study establishes a comprehensive evaluation index model encompassing economy, population, land use and land cover, society, and ecology to explore the spatiotemporal variations of RTD and the differences in the transformation mechanisms in the GNL region. The results reveal that RTD in the GNL region exhibited notable spatiotemporal variation from 2000 to 2019. Despite considerable heterogeneity in spatial distribution, regional disparities in RTD have decreased, partly due to policy implementation. Importantly, the speed and magnitude of RTD, often overlooked in previous studies, are critical indicators for assessing its reasonableness. The ecological environment is particularly significant for RTD assessment, especially in China’s ecologically fragile mountainous rural areas. Our findings suggest that promoting balanced regional development is essential in poverty-stricken areas. This study provides valuable theoretical references for planners and policymakers in implementing rural revitalization strategies.

Abstract Knee osteoarthritis (KOA) is a common chronic joint disease globally. Synovial inflammation plays a pivotal role in its pathogenesis, preceding cartilage damage. Identifying biomarkers in osteoarthritic synovial tissues holds promise for early diagnosis and targeted interventions. Gene expression profiles were obtained from the Gene Expression Omnibus database. Subsequent analyses included differential expression gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA) on the combined datasets. We performed functional enrichment analysis on the overlapping genes between DEGs and module genes and constructed a protein–protein interaction network. Using Cytoscape software, we identified hub genes related to the disease and conducted gene set enrichment analysis on these hub genes. The CIBERSORT algorithm was employed to evaluate the correlation between hub genes and the abundance of immune cells within tissues. Finally, Mendelian randomization analysis was utilized to assess the potential of these hub genes as biomarkers. We identified 46 differentially expressed genes (DEGs), comprising 20 upregulated and 26 downregulated genes. Using WGCNA, we constructed a gene co-expression network and selected the most relevant modules, resulting in 24 intersecting genes with the DEGs. KEGG enrichment analysis of the intersecting genes identified the IL-17 signaling pathway, associated with inflammation, as the most significant pathway. Cytoscape software was utilized to rank the candidate genes, with JUN, ATF3, FOSB, NR4A2, and IL6 emerging as the top five based on the Degree algorithm. A nomogram model incorporating these five genes, supported by ROC curve analysis, validated their diagnostic efficacy. Immune infiltration and correlation analysis revealed that macrophages were significantly associated with JUN (p

Abstract Background The relationship between free fatty acids (FFAs) and the risk of mortality remains unclear. There is a scarcity of prospective studies examining the associations between specific FFAs, rather than total concentrations, of their effect on long-term health outcomes. Objective To evaluate the correlation between different FFAs and all-cause and cardiovascular mortality in a large, diverse, nationally representative sample of adults in the US, and examine how different FFAs may mediate this association. Methods This cohort study included unsaturated fatty acids (USFA) and saturated fatty acids (SFA) groups in the US National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014 and provided blood samples for FFAs levels. Multiple model calibration was performed using Cox regression analysis for known risk factors to explore the associations between FFAs and all-cause and cardiovascular mortality. Results In the group of USFA, 3719 people were included, median follow-up, 6.7 years (5.8–7.8 years). In the SFA group, we included 3900 people with a median follow-up, 6.9 years (5.9-8 years). In the USFA group, myristoleic acid (14:1 n-5) (hazard ratio (HR) 1.02 [1.006–1.034]; P = 0.004), palmitoleic acid (16:1 n-7) (HR 1.001 [1.001–1.002]; P

Abstract To facilitate intelligent interconnection among people, machines, and things, the next generation of communication technology must incorporate various sensing functions besides high-speed wireless communications. Integration of radar, wireless communications, and spectrum sensing is being investigated for 6G with increased spectral efficiency, enhanced system integration, and reduced cost. Microwave photonics, a technique that combines microwave engineering and photonic technology is considered an effective solution for implementing the integration and breaking the bottleneck problems of electronic solutions. Here, we show a photonics-assisted joint radar, wireless communications, and spectrum sensing system that enables precise perception of the surrounding physical and electromagnetic environments while maintaining high-speed communication. Communication signals and frequency-sweep signals are merged optically using a shared system architecture and hardware to achieve signal level sharing, ultimately simultaneously achieving high-accuracy radar ranging and imaging with a measurement error within ± 4 cm and an imaging resolution of 25 × 24.7 mm, high-data-rate wireless communications at 2 Gbaud, and wideband spectrum sensing with a frequency measurement error within ±10 MHz in a 6 GHz bandwidth.

Abstract Background The choroid plexus (ChP) helps maintain the homeostasis of the brain by forming the blood-CSF barrier via tight junctions (TJ) at the choroid plexus epithelial cells, and subsequently preventing neuroinflammation by restricting immune cells infiltration into the central nervous system. However, whether chronic cerebral hypoperfusion causes ChP structural damage and blood-CSF barrier impairment remains understudied. Methods The bilateral carotid stenosis (BCAS) model in adult male C57BL/6 J mice was used to induce cerebral hypoperfusion, a model for vascular contributions to cognitive impairment and dementia (VCID). BCAS-mediated changes of the blood-CSF barrier TJ proteins, apical secretory Na+-K+-Cl− cotransporter isoform 1 (NKCC1) protein and regulatory serine-threonine kinases SPAK, and brain infiltration of myeloid-derived immune cells were assessed. Results BCAS triggered dynamic changes of TJ proteins (claudin 1, claudin 5) accompanied with stimulation of SPAK-NKCC1 complex and NF-κB in the ChP epithelial cells. These changes impacted the integrity of the blood-CSF barrier, as evidenced by ChP infiltration of macrophages/microglia, neutrophils and T cells. Importantly, pharmacological blockade of SPAK with its potent inhibitor ZT1a in BCAS mice attenuated brain immune cell infiltration and improved cognitive neurological function. Conclusions BCAS causes chronic ChP blood-CSF damage and immune cell infiltration. Our study sheds light on the SPAK-NKCC1 complex as a therapeutic target in neuroinflammation.

Abstract Mesenchymal stromal/stem cells (MSC) have emerged as a promising therapeutic avenue for treating autoimmune diseases, eliciting considerable interest and discussion regarding their underlying mechanisms. This study revealed the distinctive ability of human umbilical cord MSC to aggregate within the lymph nodes of mice afflicted with autoimmune diseases, but this phenomenon was not observed in healthy mice. The specific distribution is driven by the heightened expression of the CCL21-CCR7 axis in mice with autoimmune diseases, facilitating the targeted homing of MSC to the lymph nodes. Within the lymph nodes, MSC exhibit a remarkable capacity to modulate Th17 cell function, exerting a pronounced anti-inflammatory effect. Transplanted MSC stimulates the secretion of L-amino-acid oxidase (LAAO), a response triggered by elevated levels of tumor necrosis factor-α (TNF-α) in mice with autoimmune diseases through the NF-κB pathway. The presence of LAAO is indispensable for the efficacy of MSC, as it significantly contributes to the inhibition of Th17 cells. Furthermore, LAAO-derived indole-3-pyruvic acid (I3P) serves as a potent suppressor of Th17 cells by activating the aryl hydrocarbon receptor (AHR) pathway. These findings advance our understanding of the global immunomodulatory effects exerted by MSC, providing valuable information for optimizing therapeutic outcomes.

Abstract Background Long-term accumulation of misfolded proteins leads to endoplasmic reticulum (ER) stress in colorectal cancer (CRC). However, the precise pathways controlling the decision between survival and apoptosis in CRC are unclear. Therefore, in this study, we investigated the function and molecular mechanism of glucosidase I (GCS1) in regulating ER stress in CRC. Methods A public database was used to confirm the expression level of GCS1 in CRC and normal tissues. Clinical samples from our center were used to confirm the mRNA and protein expression levels of GCS1. Cell proliferation, migration, invasion, and apoptosis assays revealed the biological role of GCS1. Immunohistochemical techniques were used to evaluate the expression of key proteins in subcutaneous implanted tumors in nude mice, which provided further evidence for the biological function of GCS1 in promoting cancer in vivo. The results of coimmunoprecipitation-mass spectrometry analysis and immunofluorescence colocalization analysis the interaction between GCS1 and GRP78. In addition, the mechanism of action of USP10, GRP78, and GCS1 at the post- translational level was investigated. Finally, a tissue microarray was used to examine the connection between GCS1 and GRP78 expression and intracellular localization of these proteins using immunohistochemistry and immunofluorescence. Results The experimental results revealed that GCS1 was substantially expressed in CRC, with higher expression indicating a worse prognosis. Thus, GCS1 can enhance the proliferation and metastasis while inhibiting the apoptosis of CRC cells both in vivo and in vitro. Mechanistically, GCS1 binds to GRP78, recruits USP10 for deubiquitination of GRP78 to promote its degradation, and decreases ER stress-mediated apoptosis, increasing CRC cell proliferation and metastasis. Conclusions In summary, GCS1 stimulates CRC growth and migration and reduces ER stress-mediated apoptosis via USP10-mediated deubiquitination of GRP78. Our findings identify a possible therapeutic target for CRC.

Abstract Vertical field effect transistor (VFET), in which the semiconductor is sandwiched between source/drain electrodes and the channel length is simply determined by the semiconductor thickness, has demonstrated promising potential for short channel devices. However, despite extensive efforts over the past decade, scalable methods to fabricate ultra-short channel VFETs remain challenging. Here, we demonstrate a layer-by-layer transfer process of large-scale indium gallium zinc oxide (IGZO) semiconductor arrays and metal electrodes, and realize large-scale VFETs with ultra-short channel length and high device performance. Within this process, the oxide semiconductor could be pre-deposited on a sacrificial wafer, and then physically released and sandwiched between metals, maintaining the intrinsic properties of ultra-scaled vertical channel. Based on this lamination process, we realize 2 inch-scale VFETs with channel length down to 4 nm, on-current over 800 A/cm2, and highest on-off ratio up to 2 × 105, which is over two orders of magnitude higher compared to control samples without laminating process. Our study not only represents the optimization of VFETs performance and scalability at the same time, but also offers a method of transfer large-scale oxide arrays, providing interesting implication for ultra-thin vertical devices.

Abstract Lens-free on-chip microscopy is a powerful and promising high-throughput computational microscopy technique due to its unique advantage of creating high-resolution images across the full field-of-view (FOV) of the imaging sensor. Nevertheless, most current lens-free microscopy methods have been designed for imaging only two-dimensional thin samples. Lens-free on-chip tomography (LFOCT) with a uniform resolution across the entire FOV and at a subpixel level remains a critical challenge. In this paper, we demonstrated a new LFOCT technique and associated imaging platform based on wavelength scanning Fourier ptychographic diffraction tomography (wsFPDT). Instead of using angularly-variable illuminations, in wsFPDT, the sample is illuminated by on-axis wavelength-variable illuminations, ranging from 430 to 1200 nm. The corresponding under-sampled diffraction patterns are recorded, and then an iterative ptychographic reconstruction procedure is applied to fill the spectrum of the three-dimensional (3D) scattering potential to recover the sample’s 3D refractive index (RI) distribution. The wavelength-scanning scheme not only eliminates the need for mechanical motion during image acquisition and precise registration of the raw images but secures a quasi-uniform, pixel-super-resolved imaging resolution across the entire imaging FOV. With wsFPDT, we demonstrate the high-throughput, billion-voxel 3D tomographic imaging results with a half-pitch lateral resolution of 775 nm and an axial resolution of 5.43 μm across a large FOV of 29.85 mm2 and an imaging depth of >200 μm. The effectiveness of the proposed method was demonstrated by imaging various types of samples, including micro-polystyrene beads, diatoms, and mouse mononuclear macrophage cells. The unique capability to reveal quantitative morphological properties, such as area, volume, and sphericity index of single cell over large cell populations makes wsFPDT a powerful quantitative and label-free tool for high-throughput biological applications.

The research on the hot corrosion resistance of nickel-based superalloys is critical to determining and enhancing their service life. Therefore, this study investigates the cyclic hot corrosion behavior of GH4738 alloy coated with a mixed salt (75 wt% Na2SO4+25 wt% NaCl) at 750 °C and 800 °C. X-ray diffractometer (XRD), scanning electron microscope (SEM), energy dispersive spectrometer (EDS), and transmission electron microscope (TEM) are used to analyze the phase compositions and film structures of the corrosion products, as well as to explore the corrosion mechanism. The results show that a thicker oxide layer is formed at higher temperatures, indicating poorer hot corrosion resistance at elevated temperatures. The corrosion products form at both temperatures to show a distinct layered structure, the outer layer is mainly composed of Cr2O3 and a small amount of TiO2, while the inner layer consists of Al2O3, CrS, and TiS. In addition, it is found that the corrosion mechanism of O, S, and Cl elements in the corrosion process is synergistic and accompanied by alkaline melting.

Incomplete elevational sampling in studies of biodiversity and community assembly along elevational gradients can result in inconsistent findings and potentially inaccurate conclusions about assembly mechanisms. In this study, we conducted extensive sampling of small mammals over a 3200 m elevational gradient on Xiling Snow Mountain, Southwestern China. We integrated functional and phylogenetic diversity to determine the mechanisms structuring small mammal assemblages. Our findings indicate that taxonomic, functional, and phylogenetic diversity, along with all species richness-corrected indices of functional and phylogenetic diversity, exhibit similar hump-shaped patterns. Our results suggest that environmental filtering plays a considerable role in structuring small mammal communities at low and high elevations, while competitive exclusion governs the assembly processes at middle elevations. Human footprint, Normalized Difference Vegetation Index, precipitation seasonality and potential evapotranspiration are key drivers of small mammal diversity and community structure along elevational gradients. In summary, our study provides evidence that phylogenetic diversity is a robust surrogate for functional diversity, and challenges the recent large-scale studies that advocate a linear relationship between small mammal assembly process and elevation. We emphasize the importance of continuously documenting general patterns of small mammal diversity across entire elevational gradients in future studies.

For many years, multi-scale models of chromatin domains, such as A/B compartments, sub-compartments, topologically associated domains (TADs), sub-TADs, and loops have been popular. However, existing methods can only identify structures at a single scale and cannot partition multi-scale structures. In this paper, we proposed a method (TORNADOES) for chromatin domain partitioning based on hypergraph clustering. First, we use a density clustering algorithm to identify TADs at different scales based on Hi-C data with different resolutions. Then, by combining ChIP-seq data features and TAD results at different scales, we generate a hypergraph based on these TADs. Finally, we partition the chromatin domain structure at different scales, including A/B, A1, A2, B1, B2, and B3 based on the Laplacian matrix feature of the hypergraph. Similarity comparison experiments and ChIP-seq signal enrichment analysis are performed on the A/B region and sub-TAD levels, respectively, demonstrating that our method can identify chromatin domains with distinct features and provide a deeper understanding of the organizational patterns and functional differences in TADs at the genomic hierarchical structure. Comparative analysis of multiple cell line data shows that TORNADOES can better classify different numbers and types of compartments by changing the factors ChIP-seq data and clustering number used to characterize TAD compared to other methods. Source code for the TORNADOES method can be found at https://github.com/ghaiyan/TORNADOES.

Cerebrocardiac syndrome refers to secondary cardiac damage caused by various craniocerebral injury lesions, which can exacerbate existing heart disease. In the practice of forensic pathology, cerebral-cardiac interaction is often ignored in cases of death with a short time after craniocerebral injury, especially those with underlying heart disease. This article reviews the pathogenesis of cerebrocardiac syndrome by summarizing recent research results of cerebrocardiac syndrome at home and abroad and discusses its significance in the field of forensic medicine. The aim is to provide assistance for forensic medicine practice of cerebrocardiac syndrome.

Aiming at the problems of poor quality of restored images and large number of model parameters in the current occluded face image restoration, a lightweight face image restoration model based on multi-scale feature fusion with improved U-Net, LM-UNET, was proposed. Firstly, the original convolution was replaced by a depthwise separable convolution to enhance the feature expression ability of the model for different channels and contextual information. Secondly, a multi-scale feature attention fusion module was designed in the jump connection to fully fuse the information of different scale features, and the embedded residual block reduced the semantic gap between features to improve the repair accuracy of the model. Finally, a positional attention module was introduced to enhance the salient information of the face image, and improve the model’s effective extraction ability of facial positional pixel information of the model. The algorithm was trained, validated and tested on the occluded face dataset MFD generated based on the CK+ dataset, and the PSNR of the repaired image reached 30.49 dB and SSIM reached 96.85%. The experimental results of comparing the model with the other models show that the model has better image quality and visual effect for restoration of the face in the presence of occlusion.

Aims: This aim of this study was to analyze the detection rate of rare pathogens in bone and joint infections (BJIs) using metagenomic next-generation sequencing (mNGS), and the impact of mNGS on clinical diagnosis and treatment. Methods: A retrospective analysis was conducted on 235 patients with BJIs who were treated at our hospital between January 2015 and December 2021. Patients were divided into the no-mNGS group (microbial culture only) and the mNGS group (mNGS testing and microbial culture) based on whether mNGS testing was used or not. Results: A total of 147 patients were included in the no-mNGS group and 88 in the mNGS group. The mNGS group had a higher detection rate of rare pathogens than the no-mNGS group (21.6% vs 10.2%, p = 0.016). However, the mNGS group had lower rates of antibiotic-related complications, shorter hospital stays, and higher infection control rates compared with the no-mNGS group (p = 0.017, p = 0.003, and p = 0.028, respectively), while there was no significant difference in the duration of antibiotic use (p = 0.957). In culture-negative cases, the mNGS group had lower rates of antibiotic-related complications, shorter hospital stays, and a higher infection control rate than the no-mNGS group (p = 0.036, p = 0.033, p = 0.022, respectively), while there was no significant difference in the duration of antibiotic use (p = 0.748). Conclusion: mNGS improves detection of rare pathogens in BJIs. mNGS testing reduces antibiotic-related complications, shortens hospital stay and antibiotic use duration, and improves treatment success rate, benefits which are particularly evident in culture-negative cases. Cite this article: Bone Joint Res 2024;13(8):401–410.

Abstract Background In recent years, significant morbidity and mortality in patients with severe inflammatory bowel disease (IBD) and cytomegalovirus (CMV) have drawn considerable attention to the status of CMV infection in the intestinal mucosa of IBD patients and its role in disease progression. However, there is currently no high-throughput sequencing data for ulcerative colitis patients with CMV infection (CMV + UC), and the immune microenvironment in CMV + UC patients have yet to be explored. Method The xCell algorithm was used for evaluate the immune microenvironment of CMV + UC patients. Then, WGCNA analysis was explored to obtain the co-expression modules between abnormal immune cells and gene level or protein level. Next, three machine learning approach include Random Forest, SVM-rfe, and Lasso were used to filter candidate biomarkers. Finally, Best Subset Selection algorithms was performed to construct the diagnostic model. Results In this study, we performed transcriptomic and proteomic sequencing on CMV + UC patients to establish a comprehensive immune microenvironment profile and found 11 specific abnormal immune cells in CMV + UC group. After using multi-omics integration algorithms, we identified seven co-expression gene modules and five co-expression protein modules. Subsequently, we utilized various machine learning algorithms to identify key biomarkers with diagnostic efficacy and constructed an early diagnostic model. We identified a total of eight biomarkers (PPP1R12B, CIRBP, CSNK2A2, DNAJB11, PIK3R4, RRBP1, STX5, TMEM214) that play crucial roles in the immune microenvironment of CMV + UC and exhibit superior diagnostic performance for CMV + UC. Conclusion This 8 biomarkers model offers a new paradigm for the diagnosis and treatment of IBD patients post-CMV infection. Further research into this model will be significant for understanding the changes in the host immune microenvironment following CMV infection.

Abstract Different chemical solutions can significantly change the contact angle (CA) of soil, but few studies have studied the change rule and action mechanism of the CA from the mineral composition of soil essence. In unsaturated soil mechanics, the CA is an important parameter to calculate the wet suction between soil particles in unsaturated soil. When the chemical composition of the soil pore liquid changes, the CA will also change, which will affect the wet suction and other parameters, thus changing the macroscopic mechanical properties of the soil. In this study, the CA of air-solution-mineral phases with different solution components (pH, type and concentration of salt solution) of different minerals (quartz, orthoclase and plagioclase) were measured. The results show that the CAs of quartz, orthoclase and plagioclase all rise first and then drop with the rise of pH. The peak CAs are pH = 5, pH = 4 and pH = 3, respectively. Quartz, orthoclase and plagioclase all have valley values in different concentrations of NaCl and KCl solutions. In CaCl2 solution, only quartz has valley value, while orthoclase and plagioclase increase monotonously. Quartz in soil plays a main role in the influence of soil CA, followed by orthoclase and plagioclase. The CA of different minerals in different chemical solutions is mainly controlled by electric double layer interaction and functional groups interaction. In different salt solution environment, in addition to the above two effects, the mineral CA is also affected by the surface tension.

Abstract The sole use of single modality data often fails to capture the complex heterogeneity among patients, including the variability in resistance to anti-HER2 therapy and outcomes of combined treatment regimens, for the treatment of HER2-positive gastric cancer (GC). This modality deficit has not been fully considered in many studies. Furthermore, the application of artificial intelligence in predicting the treatment response, particularly in complex diseases such as GC, is still in its infancy. Therefore, this study aimed to use a comprehensive analytic approach to accurately predict treatment responses to anti-HER2 therapy or anti-HER2 combined immunotherapy in patients with HER2-positive GC. We collected multi-modal data, comprising radiology, pathology, and clinical information from a cohort of 429 patients: 310 treated with anti-HER2 therapy and 119 treated with a combination of anti-HER2 and anti-PD-1/PD-L1 inhibitors immunotherapy. We introduced a deep learning model, called the Multi-Modal model (MuMo), that integrates these data to make precise treatment response predictions. MuMo achieved an area under the curve score of 0.821 for anti-HER2 therapy and 0.914 for combined immunotherapy. Moreover, patients classified as low-risk by MuMo exhibited significantly prolonged progression-free survival and overall survival (log-rank test, P

Abstract In the KEYNOTE-811 study, anti-HER2 and immunotherapy treatments resulted in longer survival in HER2-positive gastric cancer patients with CPS ≥ 1, whereas CPS

Abstract Background While body mass index (BMI) defines obesity as a well-established risk factor for cardiovascular disease, the paradoxical theory of BMI suggests that obesity may indeed have a favorable impact on the prognosis of cardiovascular disease. Therefore, this study aims to assess the correlation between body shape index (ABSI), which is a novel measure of obesity, and coronary heart disease (CHD) among obese individuals in the United States. Methods The data from the National Health and Nutrition Examination Survey (NHANES) were evaluated by us for 5046 patients. We assessed the exposure variable ABSI, which includes waist circumference (WC), height, and BMI. The outcome variable was CHD. Results The cross-sectional study included a total of 5046 obese adults aged over 20 years, with an average age (standard deviation: SD) of 49.86 (16.24) years and a male proportion of 44.57%.The odds ratio (OR) values for CHD in Model 1, Model 2, 3 were found to be 2.45 (95%CI: 2.12, 2.83), 1.53 (95%CI:1.30, 1.81) and 1.31 (95%CI:1.09, 1.56) per SD increase in ABSI, respectively. In the fully adjusted model, we designated participants in the T1 group as the reference group. Our findings indicate a significant increase in the prevalence of CHD (OR:1.82, 95%CI: 1.07–3.10) only within the T3 group. Although there is an increased prevalence of CHD (OR:1.32, 95%CI: 0.77–2.29) in the T2 group, no statistically significant difference was observed. Conclusions The increase in ABSI is strongly associated with the rise in CHD prevalence among obese individuals in the United States.

Abstract Background There is ongoing debate around rate versus rhythm control strategies for managing atrial fibrillation (AF), however, much of the data comes from Western cohorts. Kerala‐AF represents the largest prospective AF cohort study from the Indian subcontinent. Objectives To compare 12‐month outcomes between rate and rhythm control strategies. Methods Patients aged ≥18 years with non‐transient AF were recruited from 53 hospitals across Kerala. Patients were stratified by rate or rhythm control. The primary outcome was a composite of all‐cause mortality, arterial thromboembolism, acute coronary syndrome or hospitalization due to heart failure or arrhythmia at 12 months. Secondary outcomes included bleeding events and individual components of the primary. Predictors of the composite outcome were analysed by logistic regression. Results A total of 2901 patients (mean age 64.6 years, 51% female) were included (2464 rate control, 437 rhythm control). Rates of the primary composite outcome did not differ between groups (29.7% vs 30.0%; p = .955), nor did any component of the primary. Bleeding outcomes were also similar (1.6% vs 1.9%; p = .848). Independent predictors of the primary composite outcome were older age (aOR 1.01; p = .013), BMI

Abstract Eleocharis dulcis (Burm. f.) Trin. ex Hensch., commonly known as Chinese water chestnut, is a traditional aquatic vegetable in China, and now is widely cultivated throughout the world because of its high nutritional value and unique tastes. Here, we report the assembly of a 493.24 Mb telomere-to-telomere (T2T) genome of E. dulcis accomplished by integrating ONT ultra-long reads, PacBio long reads and Hi-C data. The reference genome was anchored onto 111 gap-free chromosomes, containing 48.31% repeat elements and 33,493 predicted protein-coding genes. Whole genome duplication (WGD) and inter-genomic synteny analyses indicated that chromosome breakage and genome duplication in E. dulcis possibly occurred multiple times during genome evolution after its divergence from a common ancestor with Rhynchospora breviuscula at ca. 35.6 Mya. A comparative time-course transcriptome analysis of corm development revealed different patterns of gene expression between cultivated and wild accessions with the highest number of differentially expressed genes (DEGs, 15,870) at the middle swelling stage and some of the DEGs were significantly enriched for starch metabolic process.

Abstract Objective Since January 8, 2023, China has managed COVID-19 as a Class-B infectious disease, marking the epidemic's transition to a low-level stage. This study analyzes the relationship between the public's perceived a community with shared future for doctor-patient (PCSF), health self-consciousness, benefit finding, and anxiety in this stage. Additionally, it compares changes in these variables across different stages of COVID-19. Methods Using a repeated cross-sectional design, three surveys were conducted respectively in three different stages of COVID-19 in China. Specifically, the first survey was conducted in Beijing, Dalian, Zhengzhou, Heihe, and Shangrao from November 13 to 20, 2021 in the outbreak stage of COVID-19, yielding 1,252 valid responses out of 1,534 collected questionnaires. The second survey was conducted in Dalian, Zhengzhou, Heihe, Shangrao, and Lanzhou from December 1 to 19, 2021 in the stable stage of COVID-19, with 872 valid responses obtained from 1,075 collected questionnaires. The third survey was conducted in Beijing, Dalian, Zhengzhou, Heihe, Shangrao, Lanzhou, and Chengdu from January 29 to February 4, 2023 in the low epidemic level stage of COVID-19, achieving 2,113 valid responses from the 2,461 questionnaires collected. Results Unlike in the outbreak stage but similar to the stable stage, the public's anxiety, health self-consciousness and benefit finding decreased while PCSF was improved in the low epidemic level stage. Consistent with both the outbreak and stable stage, PCSF, health self-consciousness, benefit finding, and anxiety showed positive correlations in the low epidemic level stage, with health self-consciousness partially mediating the positive impact of PCSF on benefit finding. Unlike in the stable stage but similar to the outbreak stage, anxiety did not moderate the relationship between PCSF and health self-consciousness in the low epidemic level stage. Conclusions The public's health self-consciousness, benefit finding, and anxiety decreased, while PCSF increased in the low epidemic level stage. Furthermore, PCSF had a greater impact on benefit finding, and anxiety's impact on health self-consciousness was significantly reduced. Across different stages of COVID-19, PCSF directly increased benefit finding and also enhanced benefit finding by improving health self-consciousness. Thus, comprehensive intervention measures are beneficial in the low epidemic level stage.

Objective As a key structure for carrying the vehicle, the abnormal vibration of bogies has a direct impact on the service performance of rail transit trains. Therefore, it is necessary to conduct in-depth research on the fatigue of vehicle bogies. Method In response to the abnormal bogie vibration on a certain urban rail transit train, a main line passenger tracking test is conducted to analyze the dynamic stress in the key areas for the testing vehicle. Combined with the elastic mode of bogie frame, the frame vibration and main frequency of wheel-rail excitation under different track types are compared and studied. Result & Conclusion The equivalent stress (σaeq) of 17 measuring points on train bogie frame exceeds the limit of 70 MPa before wheel reprofiling, while only one measuring point exceeds the limit after wheel reprofiling. Therefore, wheel off roundness has a significant impact on the dynamic stress of the frame. The main frequency of the frame dynamic stress signal both before and after wheel reprofiling is 59 Hz in the low-frequency range, and the main frequency energy still exists after wheel reprofiling, indicating that its correlation with train running speed and wheel off roundness is relatively small. The main frequency of dynamic stress signal is above 700 Hz in the high-frequency range. Since the high-frequency σaeq is mainly within 25 MPa, its contribution to the damage of bogie frame is very small. This type of bogie frame has an elastic mode with a frequency of about 59 Hz, where motor and side beam nod in the opposite direction. The frequency of this elastic mode is consistent with the main frequency of the dynamic stress signal of vehicle dynamic stress measurement points on three track types: long sleeper integrated track bed+ZX-2 fastener, short sleeper integrated track bed+ZX-2 fastener, and floating plate track bed (high-end steel)+ZX-2 fastener. However, this main frequency does not exist on other track types, indicating that the elastic mode of the frame is excited on some track types, causing excessive fatigue damage values. The vertical vibration main frequencies of the vehicle axle box on this line are 60.5 Hz and 37.0 Hz respectively, of which 60.5 Hz is mainly generated by the coupling effect between the vehicle and the track, and 37.0 Hz has a certain correlation with the vibration damping fasteners. Therefore, the combination of track bed and fastener types has a significant impact on the wheel rail vibration.

Abstract Accurate detection of algae in microscopic image plays a crucial role in water quality monitoring. However, the existing object detection methods still face challenges in accurately detecting different categories of algae in microscopic image. In order to improve the accuracy, an improved YOLOv5s model is proposed for microalgae detection, by combining a Receptive Field Enhancement (RFE) module, the Wise‐IoU v3 dynamic non‐monotonic focal loss function, and a Dynamic head (Dyhead), which is termed receptive field enhancement wise‐IoU dyhead (RWD)‐you only look once (YOLO). Firstly, to detect microalgae of various scales, the Bottleneck in the C3 module of YOLOv5s is replaced with a more reasonable RFE module. Secondly, Wise‐IoU v3 is applied to enhance detection accuracy by assigning varying weights between high‐quality and low‐quality images. Finally, Dyhead is introduced to enhance the representation capacity of the detection head by integrating three attention mechanisms: scale awareness, spatial awareness, and task awareness. The proposed RWD‐YOLO model significantly enhances the accuracy of algae detection in microscopic image. Specifically, the experimental results on the microalgae dataset show that the RWD‐YOLO achieves an mAP@0.5 of 93.2% and an mAP@0.5:0.95 of 65.1%. Compared to the original YOLOv5s, mAP@0.5 and mAP@0.5:0.95 are improved by 3.7% and 5.7%, respectively.

Background/Aims: Metabolic-associated fatty liver disease (MAFLD) is a common cause of chronic liver disease worldwide. However, there is currently no recognized effective drugs for treating it. Materials and Methods: In this study, we investigated the efficacy of Honokiol (HNK) in vitro for mitigating MAFLD. Then, 0.4 mM palmitic acid (PA) and LO2 cells were used to establish the MAFLD model. The protective effect of HNK on MAFLD was confirmed by Oil Red O staining and cell counting kit (CCK-8) assay in LO2 cell line. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were carried out to analyze the regulatory role of HNK on Nrf2 and RIPK3 signaling pathways. The effect of HNK and its downstream signaling pathways on oxidative stress were verified by the detection of reactive oxygen species (ROS), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD). The concentration of IL-1β, IL-6L, and TNF-α was assessed by enzyme-linked immunosorbent assay (ELISA). Results: The middle concentration of HNK (50 μmol/L) was selected as the best option for inhibiting lipidosis and oxidative stress in MAFLD models. Honokiol mitigates MAFLD via activation of nuclear factor E2-related factor 2 (Nrf2) signaling pathways in vitro. Honokiol suppressed MAFLD via activating the Nrf2 signaling pathway to play an antioxidant and anti-inflammatory role. Also, HNK regulates Nrf2 and RIPK3 signaling pathways to mitigate MAFLD. Conclusion: Our results showed that HNK may suppress the oxidative stress and inflammation in MAFLD via activation of Nrf2 signaling pathway.

Abstract In this paper, we address the challenges of random label ordering and limited interpretability associated with Ensemble Classifier Chains (ECC) by introducing a novel ECC method, ECC-MOO&BN, which integrates Bayesian Networks (BN) and Multi-Objective Optimization (MOO). This approach is designed to concurrently overcome these ECC limitations. The ECC-MOO&BN method focuses on extracting diverse and interpretable label orderings for the ECC classifier. We initiated this process by employing mutual information to investigate label relationships and establish the initial structures of the BN. Subsequently, an enhanced NSGA-II algorithm was applied to develop a series of Directed Acyclic Graphs (DAGs) that effectively balance the likelihood and complexity of the BN structure. The rationale behind using the MOO method lies in its ability to optimize both complexity and likelihood simultaneously, which not only diversifies DAG generation but also helps avoid overfitting during the production of label orderings. The DAGs, once sorted topologically, yielded a series of label orderings, which were then seamlessly integrated into the ECC framework for addressing multi-label classification (MLC) problems. Experimental results show that when benchmarked against eleven leading-edge MLC algorithms, our proposed method achieves the highest average ranking across seven evaluation criteria on nine out of thirteen MLC datasets. The results of the Friedman test and Nemenyi test also indicate that the performance of the proposed method has a significant advantage compared to other algorithms.

Ferroelectric thin films based on HfO2 have garnered increasing attention worldwide, primarily due to their remarkable compatibility with silicon and scalability, in contrast to traditional perovskite-structured ferroelectric materials. Nonetheless, significant challenges remain in their widespread commercial utilization, particularly concerning their notable wake-up effect and limited endurance. To address these challenges, we propose a novel strategy involving the inhomogeneous distribution of Hf/Zr elements within thin films and explore its effects on the ferroelectricity and endurance of Hf0.5Zr0.5O2 thin films. Through techniques such as grazing incidence X-ray diffraction, transmission electron microscopy, and piezoresponse force microscopy, we investigated the structural characteristics and domain switching behaviors of these materials. The experimental results indicate that the inhomogeneous distribution of Hf/Zr contributes to improving the frequency stability and endurance while maintaining a large remnant polarization in Hf0.5Zr0.5O2 ferroelectric thin films. By adjusting the distribution of Zr/Hf within the Hf0.5Zr0.5O2 thin films, significant enhancements in the remnant polarization (2Pr > 35 μC/cm2) and endurance (> 109) along with a reduced coercive voltage can be achieved. Additionally, the fabricated ferroelectric thin films also exhibit high dielectric tunability (≥ 26%) under a low operating voltage of 2.5 V, whether in the wake-up state or not. This study offers a promising approach to optimize both the ferroelectricity and endurance of HfO2-based thin films.