Sharing massive biomedical data at magnitudes lower bandwidth using implicit neural function.

Efficient storage and sharing of massive biomedical data would open up their wide accessibility to different institutions and disciplines. However, compressors tailored for natural photos/videos are rapidly limited for biomedical data, while emerging deep learning-based methods demand huge training data and are difficult to generalize. Here, we propose to conduct Biomedical data compRession with Implicit nEural Function (BRIEF) by representing the target data with compact neural networks, which are data specific and thus have no generalization issues. Benefiting from the strong representation capability of implicit neural function, BRIEF achieves 2[Formula: see text]3 orders of magnitude compression on diverse biomedical data at significantly higher fidelity than existing techniques. Besides, BRIEF is of consistent performance across the whole data volume, and supports customized spatially varying fidelity. BRIEF's multifold advantageous features also serve reliable downstream tasks at low bandwidth. Our approach will facilitate low-bandwidth data sharing and promote collaboration and progress in the biomedical field.

African swine fever virus I73R is a critical virulence-related gene: A potential target for attenuation.

African swine fever virus (ASFV) is a large, double-stranded DNA virus that causes a fatal disease in pigs, posing a threat to the global pig industry. Whereas some ASFV proteins have been found to play important roles in ASFV-host interaction, the functional roles of many proteins are still largely unknown. In this study, we identified I73R, an early viral gene in the replication cycle of ASFV, as a key virulence factor. Our findings demonstrate that pI73R suppresses the host innate immune response by broadly inhibiting the synthesis of host proteins, including antiviral proteins. Crystallization and structural characterization results suggest that pI73R is a nucleic-acid-binding protein containing a Zα domain. It localizes in the nucleus and inhibits host protein synthesis by suppressing the nuclear export of cellular messenger RNA (mRNAs). While pI73R promotes viral replication, the deletion of the gene showed that it is a nonessential gene for virus replication. In vivo safety and immunogenicity evaluation results demonstrate that the deletion mutant ASFV-GZΔI73R is completely nonpathogenic and provides effective protection to pigs against wild-type ASFV. These results reveal I73R as a virulence-related gene critical for ASFV pathogenesis and suggest that it is a potential target for virus attenuation. Accordingly, the deletion mutant ASFV-GZΔI73R can be a potent live-attenuated vaccine candidate.

Novel mutation N588 residue in the NS1 protein of feline parvovirus greatly augments viral replication.

Feline parvovirus (FPV) infection is highly fatal in felines. NS1, which is a key nonstructural protein of FPV, can inhibit host innate immunity and promote viral replication, which is the main reason for the severe pathogenicity of FPV. However, the mechanism by which the NS1 protein disrupts host immunity and regulates viral replication is still unclear. Here, we identified an FPV M1 strain that is regulated by the NS1 protein and has more pronounced suppression of innate immunity, resulting in robust replication. We found that the neutralization titer of the FPV M1 strain was significantly lower than that of the other strains. Moreover, FPV M1 had powerful replication ability, and the FPV M1-NS1 protein had heightened efficacy in repressing interferon-stimulated genes (ISGs) expression. Subsequently, we constructed an FPV reverse genetic system, which confirmed that the N588 residue of FPV M1-NS1 protein is a key amino acid that bolsters viral proliferation. Recombinant virus containing N588 also had stronger ability to inhibit ISGs, and lower ISGs levels promoted viral replication and reduced the neutralization titer of the positive control serum. Finally, we confirmed that the difference in viral replication was abolished in type I IFN receptor knockout cell lines. In conclusion, our results demonstrate that the N588 residue of the NS1 protein is a critical amino acid that promotes viral proliferation by increasing the inhibition of ISGs expression. These insights provide a reference for studying the relationship between parvovirus-mediated inhibition of host innate immunity and viral replication while facilitating improved FPV vaccine production.IMPORTANCEFPV infection is a viral infectious disease with the highest mortality rate in felines. A universal feature of parvovirus is its ability to inhibit host innate immunity, and its ability to suppress innate immunity is mainly accomplished by the NS1 protein. In the present study, FPV was used as a viral model to explore the mechanism by which the NS1 protein inhibits innate immunity and regulates viral replication. Studies have shown that the FPV-NS1 protein containing the N588 residue strongly inhibits the expression of host ISGs, thereby increasing the viral proliferation titer. In addition, the presence of the N588 residue can increase the proliferation titer of the strain 5- to 10-fold without affecting its virulence and immunogenicity. In conclusion, our findings provide new insights and guidance for studying the mechanisms by which parvoviruses suppress innate immunity and for developing high-yielding FPV vaccines.

Upregulation of proBDNF/p75NTR signaling in immune cells and its correlation with inflammatory markers in patients with major depression.

ProBDNF is the precursor protein of brain-derived neurotrophic factor (BDNF) expressed in the central nervous system and peripheral tissues. Previous studies showed that the blood levels of both proBDNF and p75 neurotrophic receptors (p75NTR) in major depressive disorder (MDD) were increased, but which blood cell types express proBDNF and its receptors is not known. Furthermore, the relationship between proBDNF/p75NTR and inflammatory cytokines in peripheral blood of MDD is unclear. Peripheral blood mononuclear cells (PBMCs) and serum were obtained from depressive patients (n = 32) and normal donors (n = 20). We examined the expression of proBDNF and inflammatory markers and their correlative relationship in patients with major depression. Using flow cytometry analysis, we examined which blood cells express proBDNF and its receptors. Finally, the role of proBDNF/p75NTR signal in inflammatory immune activity of PBMCs was verified in vitro experiments. Inflammatory cytokines in PBMC from MDD patients were increased and correlated with the major depression scores. The levels of IL-1ß and IL-10 were also positively correlated with the major depression scores, while the levels of TNF-α and IL-6 were negatively correlated with the major depression scores. Intriguingly, the levels of sortilin were positively correlated with IL-1ß. Q-PCR and Western blots showed proBDNF, p75NTR, and sortilin levels were significantly increased in PBMCs from MDD patients compared with that from the normal donors. Flow cytometry studies showed that proBDNF and p75NTR were present mainly in CD4+ and CD8+ T cells. The number of proBDNF and p75NTR positive CD4+ and CD8+ T cells from MDD patients was increased and subsequently reversed after therapeutic management. Exogenous proBDNF protein or p75ECD-Fc treatment of cultured PBMC affected the release of inflammatory cytokines in vitro. ProBDNF promoted the expression of inflammatory cytokines, while p75ECD-Fc inhibited the expression of inflammatory cytokines. Given there was an inflammatory response of lymphocytes to proBDNF, it is suggested that proBDNF/p75NTR signaling may upstream inflammatory cytokines in MDD. Our data suggest that proBDNF/p75NTR signaling may not only serve as biomarkers but also may be a potential therapeutic target for MDD.

Development of an improved inhibitor of Lats kinases to promote regeneration of mammalian organs.

The Hippo signaling pathway acts as a brake on regeneration in many tissues. This cascade of kinases culminates in the phosphorylation of the transcriptional cofactors Yap and Taz, whose concentration in the nucleus consequently remains low. Various types of cellular signals can reduce phosphorylation, however, resulting in the accumulation of Yap and Taz in the nucleus and subsequently in mitosis. We earlier identified a small molecule, TRULI, that blocks the final kinases in the pathway, Lats1 and Lats2, and thus elicits proliferation of several cell types that are ordinarily postmitotic and aids regeneration in mammals. In the present study, we present the results of chemical modification of the original compound and demonstrate that a derivative, TDI-011536, is an effective blocker of Lats kinases in vitro at nanomolar concentrations. The compound fosters extensive proliferation in retinal organoids derived from human induced pluripotent stem cells. Intraperitoneal administration of the substance to mice suppresses Yap phosphorylation for several hours and induces transcriptional activation of Yap target genes in the heart, liver, and skin. Moreover, the compound initiates the proliferation of cardiomyocytes in adult mice following cardiac cryolesions. After further chemical refinement, related compounds might prove useful in protective and regenerative therapies.

Stable Zinc Anode Facilitated by Regenerated Silk Fibroin-modified Hydrogel Protective Layer.

Inherent dendrite growth and side reactions of zinc anode caused by its unstable interface in aqueous electrolytes severely limit the practical applications of zinc-ion batteries (ZIBs). To overcome these challenges, a protective layer for Zn anode inspired by cytomembrane structure is developed with PVA as framework and silk fibroin gel suspension (SFs) as modifier. This PVA/SFs gel-like layer exerts similar to the solid electrolyte interphase, optimizing the anode-electrolyte interface and Zn2+ solvation structure. Through interface improvement, controlled Zn2+ migration/diffusion, and desolvation, this buffer layer effectively inhibits dendrite growth and side reactions. The additional SFs provide functional improvement and better interaction with PVA by abundant functional groups, achieving a robust and durable Zn anode with high reversibility. Thus, the PVA/SFs@Zn symmetric cell exhibits an ultra-long lifespan of 3150 h compared to bare Zn (182 h) at 1.0 mAh cm-2-1.0 mAh cm-2, and excellent reversibility with an average Coulombic efficiency of 99.04% under a large plating capacity for 800 cycles. Moreover, the PVA/SFs@Zn||PANI/CC full cells maintain over 20 000 cycles with over 80% capacity retention under harsh conditions at 5 and 10 A g-1. This SF-modified protective layer for Zn anode suggests a promising strategy for reliable and high-performance ZIBs.

Critical Review of Emerging Pre-metallization Technologies for Rechargeable Metal-Ion Batteries.

Low Coulombic efficiency, low-capacity retention, and short cycle life are the primary challenges faced by various metal-ion batteries due to the loss of corresponding active metal. Practically, these issues can be significantly ameliorated by compensating for the loss of active metals using pre-metallization techniques. Herein, the state-of-the-art development in various pr-emetallization techniques is summarized. First, the origin of pre-metallization is elaborated and the Coulombic efficiency of different battery materials is compared. Second, different pre-metallization strategies, including direct physical contact, chemical strategies, electrochemical method, overmetallized approach, and the use of electrode additives are summarized. Third, the impact of pre-metallization on batteries, along with its role in improving Coulombic efficiency is discussed. Fourth, the various characterization techniques required for mechanistic studies in this field are outlined, from laboratory-level experiments to large scientific device. Finally, the current challenges and future opportunities of pre-metallization technology in improving Coulombic efficiency and cycle stability for various metal-ion batteries are discussed. In particular, the positive influence of pre-metallization reagents is emphasized in the anode-free battery systems. It is envisioned that this review will inspire the development of high-performance energy storage systems via the effective pre-metallization technologies.

Analysis of the Trends and Influencing Factors for Postoperative Cough in Patients with Esophageal Cancer Based on Patient-Reported Outcomes.

BACKGROUND: Cough is a common symptom that affects patients' recovery and quality of life after esophagectomy. This study sought to investigate trends in postoperative cough and the factors that influence cough. METHODS: A total of 208 of 225 patients were enrolled in this study. The Mandarin Chinese version of the Leicester Cough Questionnaire was administered the day before surgery and at three time points (1 week, 1 month, and 3 months) after esophagectomy to assess patient-reported outcomes. RESULTS: All patients' LCQ-MC scores after surgery were lower than presurgery (P < 0.05), with the lowest score found 1 week after esophagectomy. Factors associated with a cough 1 week after surgery included clinical stage of cancer (OR 0.782, 95% CI 0.647-0.944, P = 0.011), anastomotic position (OR 1.241, 95% CI 1.069-1.441, P = 0.005), duration of surgery (OR 0.759, 95% CI 0.577-0.998, P = 0.049), and subcarinal lymph node dissection (OR 0.682, 95% CI 0.563-0.825, P < 0.001). Factors associated with a cough one month after surgery included clinical stage (OR 0.782, 95% CI 0.650-0.940, P = 0.009), anastomotic position (OR 1.293, 95% CI 1.113-1.503, P = 0.001), and maintaining a semi-reclining position (OR 1.440, 95% CI 1.175-1.766, P < 0.001). Factors associated with a cough 3 months after surgery were clinical stage (OR 0.741, 95% CI 0.591-0.928, P = 0.009) and anastomotic position (OR 1.220, 95% CI 1.037-1.435, P = 0.016). CONCLUSIONS: This study showed that the factors influencing postoperative cough differed over time following esophagectomy. These results may warrant prospective intervention to better manage patients undergoing surgery for esophageal cancer to prevent postoperative cough.

Enhanced Artificial Intelligence Strategies in Renal Oncology: Iterative Optimization and Comparative Analysis of GPT 3.5 Versus 4.0.

BACKGROUND: The rise of artificial intelligence (AI) in medicine has revealed the potential of ChatGPT as a pivotal tool in medical diagnosis and treatment. This study assesses the efficacy of ChatGPT versions 3.5 and 4.0 in addressing renal cell carcinoma (RCC) clinical inquiries. Notably, fine-tuning and iterative optimization of the model corrected ChatGPT's limitations in this area. METHODS: In our study, 80 RCC-related clinical questions from urology experts were posed three times to both ChatGPT 3.5 and ChatGPT 4.0, seeking binary (yes/no) responses. We then statistically analyzed the answers. Finally, we fine-tuned the GPT-3.5 Turbo model using these questions, and assessed its training outcomes. RESULTS: We found that the average accuracy rates of answers provided by ChatGPT versions 3.5 and 4.0 were 67.08% and 77.50%, respectively. ChatGPT 4.0 outperformed ChatGPT 3.5, with a higher accuracy rate in responses (p < 0.05). By counting the number of correct responses to the 80 questions, we then found that although ChatGPT 4.0 performed better (p < 0.05), both versions were subject to instability in answering. Finally, by fine-tuning the GPT-3.5 Turbo model, we found that the correct rate of responses to these questions could be stabilized at 93.75%. Iterative optimization of the model can result in 100% response accuracy. CONCLUSION: We compared ChatGPT versions 3.5 and 4.0 in addressing clinical RCC questions, identifying their limitations. By applying the GPT-3.5 Turbo fine-tuned model iterative training method, we enhanced AI strategies in renal oncology. This approach is set to enhance ChatGPT's database and clinical guidance capabilities, optimizing AI in this field.

PHLDA1 is a P53 target gene involved in P53-mediated cell apoptosis.

Pleckstrin homeolike domain, family A, member 1 (PHLDA1) is a multifunctional protein that plays diverse roles in A variety of biological processes, including cell death, and hence its altered expression has been found in different types of cancer. Although studies have shown a regulatory relationship between p53 and PHLDA1, the molecular mechanism is still unclear. Especially, the role of PHLDA1 in the process of apoptosis is still controversial. In this study, we found that the expression of PHLDA1 in human cervical cancer cell lines was correlated with the up-expression of p53 after treatment with apoptosis-inducing factors. Subsequently, the binding site and the binding effect of p53 on the promoter region of PHLDA1 were verified by our bioinformatics data analysis and luciferase reporter assay. Indeed, we used CRISPR-Cas9 to knockout the p53 gene in HeLa cells and further confirmed that p53 can bind to the promoter region of PHLDA1 gene, and then directly regulate the expression of PHLDA1 by recruiting P300 and CBP to change the acetylation and methylation levels in the promoter region. Finally, a series of gain-of-function experiments further confirmed that p53 re-expression in HeLap53-/- cell can up-regulate the reduction of PHLDA1 caused by p53 knockout, and affect cell apoptosis and proliferation. Our study is the first to explore the regulatory mechanism of p53 on PHLDA1 by using the p53 gene knockout cell model, which further proves that PHLDA1 is a target-gene in p53-mediated apoptosis, and reveals the important role of PHLDA1 in cell fate determination.

Dysregulated inflammatory response to urogynecologic meshes in women with diabetes and its implications.

BACKGROUND: Diabetes is an independent risk factor for mesh complications in women undergoing mesh-augmented surgical repairs of stress urinary incontinence and/or pelvic organ prolapse. The underlying mechanism remains unclear. OBJECTIVE: This study aimed to define the diabetes-associated alterations in the host inflammatory response to mesh and correlate them with perioperative glucose management. STUDY DESIGN: Deidentified demographics and medical records of patients who underwent mesh removal and participated in a mesh biorepository study were reviewed (n=200). In patients with diagnosed diabetes (n=25), blood glucose management before initial mesh implantation and before and after mesh removal was assessed by blood glucose and hemoglobin A1c levels. Age- and body mass index-matched tissue samples excised from patients with and without diabetes were examined. Transcriptomic profiles of immune cell markers, immune mediators, key inflammatory regulators, cell senescence, and epigenetic enzymes were determined by multiplex transcriptomic assays (NanoString). Ratios of apoptotic cells to CD68+ macrophages were examined with immunofluorescence. Protein profiles of 12 molecules involved in apoptotic cell clearance were examined with a multiplex protein assay (Luminex). RESULTS: Demographic and clinical characteristics, including duration between mesh implantation and removal, reason for removal, and type of mesh, etc., were comparable between patients with and without diabetes, except for 11.6% higher body mass index in the former (P=.005). In patients with diabetes, suboptimal management of blood glucose following mesh implantation was observed, with 59% of the patients having loosely or poorly controlled glucose before and after the mesh removal. Ongoing chronic inflammatory response was observed in the excised mesh-tissue complexes in both groups, whereas markers for M2 macrophages (Mrc1 [mannose receptor C-type 1]) and helper T cells (Cd4 [CD4 molecule]) were increasingly expressed in the diabetic vs nondiabetic group (P=.023 and .047, respectively). Furthermore, the gene expressions of proinflammatory Ccl24 (C-C motif chemokine ligand 24) and Ccl13 (C-C motif chemokine ligand 13) were upregulated by 1.5- and 1.8-fold (P=.035 and .027, respectively), whereas that of Il1a (interleukin 1 alpha) was paradoxically downregulated by 2.2-fold (P=.037) in the diabetic vs nondiabetic group. Interestingly, strong positive correlations were found between the expression of Ccl13, Setdb2 (SET domain bifurcated histone lysine methyltransferase 2), and M2 macrophage markers, and between the expression of Il1a, Fosl1 (activator protein-1 transcription factor subunit), and dendritic cell markers, suggesting the involvement of macrophages and dendritic cells in the diabetes-dysregulated proinflammatory response. Supportively, apoptotic cell clearance, which is an important function of macrophages, appeared to be impaired in the diabetic group, with a significantly increased protein level of CALR (calreticulin), an "eat-me" signal on the surface of apoptotic cells (P=.031), along with an increase of AXL (AXL receptor tyrosine kinase) (P=.030), which mediates apoptotic cell clearance. CONCLUSION: Diabetes was associated with altered long-term inflammatory response in complicated mesh implantation, particularly involving innate immune cell dysfunction. Suboptimal blood glycemic control following mesh implantation may contribute to this immune dysregulation, necessitating further mechanistic studies.

Diagnostic test accuracy of serum creatinine and cystatin C-based index for sarcopenia: a systematic review and meta-analysis.

BACKGROUND: Sarcopenia is an important prognostic factor, but its optimal screening methods remain challenging. Several new indices developed based on serum creatinine (Cr) and cystatin C (CysC) have been proposed to be diagnostic biomarkers for sarcopenia screening. OBJECTIVE: This review aimed to evaluate the diagnostic accuracy of serum Cr- and CysC-based indices for sarcopenia diagnosis. METHODS: We systematically searched MEDLINE, EMBASE, SCIE and SCOPUS from inception to 2 April 2023. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A bivariate random-effects model was used to synthesise the pooled sensitivity, specificity and area under the curves of the summary receiver operating characteristic (SROC-AUC). RESULTS: We retrieved 936 publications and included 16 studies with 5,566 participants (mean age ranged: 51.0-78.4 years, 50.2% men). The prevalence of sarcopenia ranged from 7.8 to 69.5%. All included studies presented a moderate to high risk of bias. The serum Cr- and CysC-based indices showed moderate diagnostic accuracy for sarcopenia (pooled sensitivity: 0.67, 95% CI 0.57-0.75; pooled specificity: 076, 95% CI 0.67-0.83; pooled SROC-AUC: 0.78, 95% CI 0.74-0.81). The Cr/CysC ratio is the most widely studied index, followed by the Cr × eGFRcys index. Overall, both indicators had satisfactory and comparable performance in screening sarcopenia. CONCLUSION: Serum Cr- and CysC-based indices showed moderate diagnostic accuracy for sarcopenia. The most studied indices-the Cr/CysC ratio and Cr × eGFRcys index-had comparable diagnostic accuracy for evaluating sarcopenia and may serve as surrogate markers for sarcopenia. However, further validation is required to verify these findings.

The combination of modified acupuncture needle and melittin hydrogel as a novel therapeutic approach for rheumatoid arthritis treatment.

Rheumatoid arthritis (RA) involves chronic joint inflammation. Combining acupuncture and medication for RA treatment faces challenges like spatiotemporal variability, limited drug loading in acupuncture needles, and premature or untargeted drug release. Here, we designed a new type of tubular acupuncture needles, with an etched hollow honeycomb-like structure to enable the high loading of therapeutics, integrating the traditional acupuncture and drug repository into an all-in-one therapeutic platform. In these proof-of-concept experiments, we fabricated injectable hollow honeycomb electroacupuncture needles (HC-EA) loaded with melittin hydrogel (MLT-Gel), enabling the combination treatment of acupuncture stimulation and melittin therapy in a spatiotemporally synchronous manner. Since the RA microenvironment is mildly acidic, the acid-responsive chitosan (CS)/sodium beta-glycerophosphate (ß-GP)/ hyaluronic acid (HA) composited hydrogel (CS/GP/HA) was utilized to perform acupuncture stimulation and achieve the targeted release of injected therapeutics into the specific lesion site. Testing our therapeutic platform involved a mouse model of RA and bioinformatics analysis. MLT-Gel@HC-EA treatment restored Th17/Treg-mediated immunity balance, reduced inflammatory factor release (TNF-α, IL-6, IL-1ß), and alleviated inflammation at the lesion site. This novel combination of modified acupuncture needle and medication, specifically melittin hydrogel, holds promise as a therapeutic strategy for RA treatment.

Creatinine-to-cystatin C ratio and frailty in older adults: a longitudinal cohort study.

BACKGROUND: Creatinine-to-cystatin C ratio (CCR) has been associated with multiple adverse outcomes. However, little is known about its relationship with frailty. We aimed to explore the association between CCR and frailty among older adults. METHODS: A total of 2599 participants aged ≥ 60 years (mean age 67.9 ± 6.0 years, 50.4% males) were included from the China Health and Retirement Longitudinal Study (2011-2015). Baseline CCR was calculated as plasma creatinine (mg/dL) / cystatin C (mg/L) × 10 and was grouped by quartiles. Frailty was evaluated by the validated physical frailty phenotype (PFP) scale and was defined as PFP score ≥ 3. The generalized estimating equations model was used to explore the relationship between CCR and frailty. RESULTS: The frailty risk decreased gradually with increasing CCR in the quartiles (P for trend = 0.002), and the fourth CCR quartile was associated with a significantly lower risk of frailty compared with the lowest quartile (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.19-0.70). When modeling as a continuous variable, per 1-unit increase in CCR was related to 17% decreased odds of frailty (OR 0.83, 95% CI 0.74-0.93). The association was consistent in male and female participants (P for interaction = 0.41). Poisson models revealed that frailty score was negatively associated with CCR (ß= -0.11, 95% CI= -0.19 to -0.04), and sex did not significantly moderate the associations (P for interaction = 0.22). The results were not affected by further adjusting for high-sensitivity C-reactive protein. Similar results were observed by analyses with multiple imputation technique and analyses excluding participants with baseline frailty. CONCLUSIONS: Higher CCR was associated with a lower frailty risk. CCR may be a simple marker for predicting frailty in older adults.

Development and validation of a predictive model for end-stage renal disease in systemic lupus erythematosus patients.

Systemic lupus erythematosus (SLE) affects many populations. This study aims to develop a predictive model and create a nomogram for assessing the risk of end-stage renal disease (ESRD) in patients diagnosed with SLE. Data from electronic health records of SLE patients treated at the Affiliated Hospital of North Sichuan Medical College between 2013 and 2023 were collected. The dataset underwent thorough cleaning and variable assignment procedures. Subsequently, variables were selected using one-way logistic regression and lasso logistic regression methods, followed by multifactorial logistic regression to construct nomograms. The model's performance was assessed using calibration, receiver operating characteristic (ROC), and decision curve analysis (DCA) curves. Statistical significance was set at P < 0.05. The predictive variables for ESRD development in SLE patients included anti-GP210 antibody presence, urinary occult blood, proteinuria, white blood cell count, complement 4 levels, uric acid, creatinine, total protein, globulin, glomerular filtration rate, pH, specific gravity, very low-density lipoprotein, homocysteine, apolipoprotein B, and absolute counts of cytotoxic T cells. The nomogram exhibited a broad predictive range. The ROC area under the curve (AUC) was 0.886 (0.858-0.913) for the training set and 0.840 (0.783-0.897) for the testing set, indicating good model performance. The model demonstrated both applicability and significant clinical benefits. The developed model presents strong predictive capabilities and considerable clinical utility in estimating the risk of ESRD in patients with SLE.

The geriatric nutrition risk index is longitudinally associated with incident Sarcopenia: evidence from a 5-year prospective cohort.

BACKGROUND: Previous studies investigating the association between the geriatric nutrition risk index (GNRI) and sarcopenia either lacked longitudinal evidence or narrowly focused on specific populations. AIMS: We aimed to reveal longitudinal associations of GNRI with sarcopenia risk in community-dwelling Chinese. We also investigated interaction effects of potential factors on such associations. METHODS: We included participants aged ≥ 50 years with sufficient data from the WCHAT study who did not have sarcopenia at baseline and completed sarcopenia assessment during follow-up. GNRI was calculated according to the formula based on serum albumin, height and weight. Sarcopenia was diagnosed according to the 2019 AWGS consensus. Longitudinal associations between GNRI and sarcopenia were estimated by logistic regression with GNRI as either a continuous or categorical variable by tertiles, using generalized estimating equations (GEE) as sensitivity analyses. Subgroup analyses by potential covariates were conducted to detect interaction effects. RESULTS: A total of 1907 participants without baseline sarcopenia were finally included, of whom 327 (17.1%) developed incident sarcopenia during 5-year follow-up. After controlling for confounders, sarcopenia risk decreased with each one standard deviation increase in GNRI (ORadjusted=0.36, 95% CI 0.31-0.43), and it also decreased successively from the lowest (< 111.2) through middle (111.2-117.7) to the highest (≥ 117.8) tertile of the GNRI level (P for trend < 0.001). Similar results were yielded by GEE. Such associations generally remained robust across subgroups with distinct characteristics, while significant differences were observed between different age groups (≥ 65 vs. <65 years) (interaction P-value < 0.05). CONCLUSION: GNRI is longitudinally associated with sarcopenia risk with possibly age-specific differences in association magnitude, which holds implications for policymakers to conduct population-based risk assessment.

Calcitriol alleviates noise-induced hearing loss by regulating the ATF3/DUSP1 signalling pathway.

BACKGROUND: Calcitriol (Cal) is the most active metabolite of vitamin D and has antioxidant and anti-inflammatory properties. The aim of this study was to investigate the role of Cal in noise-induced hearing loss (NIHL) to further elucidate the mechanism of noise-induced oxidative stress in the mouse cochlea. METHODS: C57BL/6 J mice were given six intraperitoneal injections of Cal (500 ng/kg/d). After 14 days of noise exposure, auditory brainstem response (ABR) thresholds, and the cochlear outer hair cell loss rate were analysed to evaluate auditory function. Real-time fluorescence quantitative PCR, immunofluorescence and western blotting were performed in vitro after the treatment of cochlear explants with 100 µM tert-butyl hydroperoxide (TBHP) for 2.5 h and HEI-OC1 cells with 250 µM TBHP for 1.5 h. RESULTS: In vivo experiments confirmed that Cal pretreatment mitigated NIHL and outer hair cell death. The in vitro results demonstrated that Cal significantly reduced TBHP-induced cochlear auditory nerve fibre degradation and spiral ganglion neuron damage. Moreover, treatment with Cal inhibited the expression of oxidative stress-related factors (3-NT and 4-HNE) and DNA damage-related factors (γ-H2A.X) and attenuated TBHP-induced apoptosis in cochlear explants and HEI-OC1 cells. A total of 1479 upregulated genes and 1443 downregulated genes were screened in cochlear tissue 1 h after noise exposure. The level of transcription factor 3 (ATF3) was significantly elevated in HEI-OC1 cells after TBHP stimulation. Gene Transcription Regulation Database （GTRD）and Cistrome database analyses revealed that the downstream target gene of ATF3 is dual specificity phosphatase 1 (DUSP1). Cistrome DB Toolkit database results showed that the transcription factor of DUSP1 was ATF3. In addition, the ChIP-PCR results indicated that ATF3 might be a direct transcription factor of DUSP1. CONCLUSION: The results of our study suggest that Cal attenuates NIHL and inhibits noise-induced apoptosis by regulating the ATF3/DUSP1 signalling pathway.

A WKNN Indoor Fingerprint Localization Technique Based on Improved Discrimination Capability of RSS Similarity.

There are various indoor fingerprint localization techniques utilizing the similarity of received signal strength (RSS) to discriminate the similarity of positions. However, due to the varied states of different wireless access points (APs), each AP's contribution to RSS similarity varies, which affects the accuracy of localization. In our study, we analyzed several critical causes that affect APs' contribution, including APs' health states and APs' positions. Inspired by these insights, for a large-scale indoor space with ubiquitous APs, a threshold was set for all sample RSS to eliminate the abnormal APs dynamically, a correction quantity for each RSS was provided by the distance between the AP and the sample position to emphasize closer APs, and a priority weight was designed by RSS differences (RSSD) to further optimize the capability of fingerprint distances (FDs, the Euclidean distance of RSS) to discriminate physical distance (PDs, the Euclidean distance of positions). Integrating the above policies for the classical WKNN algorithm, a new indoor fingerprint localization technique is redefined, referred to as FDs' discrimination capability improvement WKNN (FDDC-WKNN). Our simulation results showed that the correlation and consistency between FDs and PDs are well improved, with the strong correlation increasing from 0 to 76% and the high consistency increasing from 26% to 99%, which confirms that the proposed policies can greatly enhance the discrimination capabilities of RSS similarity. We also found that abnormal APs can cause significant impact on FDs discrimination capability. Further, by implementing the FDDC-WKNN algorithm in experiments, we obtained the optimal K value in both the simulation scene and real library scene, under which the mean errors have been reduced from 2.2732 m to 1.2290 m and from 4.0489 m to 2.4320 m, respectively. In addition, compared to not using the FDDC-WKNN, the cumulative distribution function (CDF) of the localization errors curve converged faster and the error fluctuation was smaller, which demonstrates the FDDC-WKNN having stronger robustness and more stable localization performance.

Performance Study of F-P Pressure Sensor Based on Three-Wavelength Demodulation: High-Temperature, High-Pressure, and High-Dynamic Measurements.

F-P (Fabry-Perot) pressure sensors have a wide range of potential applications in high-temperature, high-pressure, and high-dynamic environments. However, existing demodulation methods commonly rely on spectrometers, which limits their application to high-frequency pressure signal acquisition. To solve this problem, this study developed a self-compensated, three-wavelength demodulation system composite with an F-P pressure sensor and a thermocouple to construct a comprehensive sensing system. The system produces accurate pressure measurements in high-temperature, high-pressure, and high-dynamic environments. In static testing at room temperature, the sensing system shows excellent linearity, and the pressure sensitivity is 158.48 nm/MPa. In high-temperature testing, the sensing system maintains high linearity in the range of 100 °C to 700 °C, with a maximum pressure-indication error of about 0.13 MPa (0~5 MPa). In dynamic testing, the sensor exhibits good response characteristics at 1000 Hz and 5000 Hz sinusoidal pressure frequencies, with a signal-to-noise ratio (SNR) greater than 37 dB and 45 dB, respectively. These results indicate that the sensing system proposed in this study has significant competitive advantages in the field of high-temperature, high-speed, and high-precision pressure measurements and provides an important experimental basis and theoretical support for technological progress in related fields.

Plasmonic-Enhanced Bright Single Spin Defects in Silicon Carbide Membranes.

Optically addressable spin defects in silicon carbide (SiC) have emerged as attractable platforms for various quantum technologies. However, the low photon count rate significantly limits their applications. We strongly enhanced the brightness by 7 times and spin-control strength by 14 times of single divacancy defects in 4H-SiC membranes using a surface plasmon generated by gold film coplanar waveguides. The mechanism of the plasmonic-enhanced effect is further studied by tuning the distance between single defects and the surface of the gold film. A three-energy-level model is used to determine the corresponding transition rates consistent with the enhanced brightness of single defects. Lifetime measurements also verified the coupling between defects and surface plasmons. Our scheme is low-cost, without complicated microfabrication and delicate structures, which is applicable for other spin defects in different materials. This work would promote developing spin-defect-based quantum applications in mature SiC materials.