SARS-CoV-2 RNA stabilizes host mRNAs to elicit immunopathogenesis.

SARS-CoV-2 RNA interacts with host factors to suppress interferon responses and simultaneously induces cytokine release to drive the development of severe coronavirus disease 2019 (COVID-19). However, how SARS-CoV-2 hijacks host RNAs to elicit such imbalanced immune responses remains elusive. Here, we analyzed SARS-CoV-2 RNA in situ structures and interactions in infected cells and patient lung samples using RIC-seq. We discovered that SARS-CoV-2 RNA forms 2,095 potential duplexes with the 3' UTRs of 205 host mRNAs to increase their stability by recruiting RNA-binding protein YBX3 in A549 cells. Disrupting the SARS-CoV-2-to-host RNA duplex or knocking down YBX3 decreased host mRNA stability and reduced viral replication. Among SARS-CoV-2-stabilized host targets, NFKBIZ was crucial for promoting cytokine production and reducing interferon responses, probably contributing to cytokine storm induction. Our study uncovers the crucial roles of RNA-RNA interactions in the immunopathogenesis of RNA viruses such as SARS-CoV-2 and provides valuable host targets for drug development.

Interpretation of 10 years of Alzheimer's disease genetic findings in the perspective of statistical heterogeneity.

Common genetic variants and susceptibility loci associated with Alzheimer's disease (AD) have been discovered through large-scale genome-wide association studies (GWAS), GWAS by proxy (GWAX) and meta-analysis of GWAS and GWAX (GWAS+GWAX). However, due to the very low repeatability of AD susceptibility loci and the low heritability of AD, these AD genetic findings have been questioned. We summarize AD genetic findings from the past 10 years and provide a new interpretation of these findings in the context of statistical heterogeneity. We discovered that only 17% of AD risk loci demonstrated reproducibility with a genome-wide significance of P < 5.00E-08 across all AD GWAS and GWAS+GWAX datasets. We highlighted that the AD GWAS+GWAX with the largest sample size failed to identify the most significant signals, the maximum number of genome-wide significant genetic variants or maximum heritability. Additionally, we identified widespread statistical heterogeneity in AD GWAS+GWAX datasets, but not in AD GWAS datasets. We consider that statistical heterogeneity may have attenuated the statistical power in AD GWAS+GWAX and may contribute to explaining the low repeatability (17%) of genome-wide significant AD susceptibility loci and the decreased AD heritability (40-2%) as the sample size increased. Importantly, evidence supports the idea that a decrease in statistical heterogeneity facilitates the identification of genome-wide significant genetic loci and contributes to an increase in AD heritability. Collectively, current AD GWAX and GWAS+GWAX findings should be meticulously assessed and warrant additional investigation, and AD GWAS+GWAX should employ multiple meta-analysis methods, such as random-effects inverse variance-weighted meta-analysis, which is designed specifically for statistical heterogeneity.

The ATF4-RPS19BP1 axis modulates ribosome biogenesis to promote erythropoiesis.

ABSTRACT: Hematopoietic differentiation is controlled by intrinsic regulators and the extrinsic hematopoietic niche. Activating transcription factor 4 (ATF4) plays a crucial role in the function of fetal and adult hematopoietic stem cell maintenance. However, the precise function of ATF4 in the bone marrow (BM) niche and the mechanism by which ATF4 regulates adult hematopoiesis remain largely unknown. Here, we used 4 cell-type-specific mouse Cre lines to achieve conditional knockout of Atf4 in Cdh5+ endothelial cells, Prx1+ BM stromal cells, Osx+ osteoprogenitor cells, and Mx1+ hematopoietic cells and uncovered the role of Atf4 in niche cells and hematopoiesis. Intriguingly, depletion of Atf4 in niche cells did not affect hematopoiesis; however, Atf4-deficient hematopoietic cells exhibited erythroid differentiation defects, leading to hypoplastic anemia. Mechanistically, ATF4 mediated direct regulation of Rps19bp1 transcription, which is, in turn, involved in 40 S ribosomal subunit assembly to coordinate ribosome biogenesis and promote erythropoiesis. Finally, we demonstrate that under conditions of 5-fluorouracil-induced stress, Atf4 depletion impedes the recovery of hematopoietic lineages, which requires efficient ribosome biogenesis. Taken together, our findings highlight the indispensable role of the ATF4-RPS19BP1 axis in the regulation of erythropoiesis.

Boolean map and object reconcile as the unit of visual working memory.

The unit of visual working memory is a fundamental issue under debate in the fields of cognitive psychology and neuroscience, with some traditional research suggesting that it is an object, while other recent studies demonstrating that a Boolean map offers a better account. The controversy surrounding the unit of visual working memory often centers on the representation of objects consist of same dimensional features (e.g. bicolor objects). For 2 colors in a bicolor object, some behavioral studies have suggested that they need to be represented by separate units, while some other studies using electrophysiological measures have found that they can be represented within a single unit. This apparent conflict hints that Boolean map and object may reconcile as the unit of visual working memory. Adopting the contralateral delay activity as an electrophysiological marker of visual working memory, experiments 1 and 2 consistently found that the contralateral delay activity amplitude for memorizing bicolor circles at P7/P8 conformed the Boolean map-based storage throughout the whole maintenance, while the contralateral delay activity amplitude at P3/P4 just conformed the object-based storage during the early period. It suggests though Boolean map got stronger supporting evidence than object, they 2 may coexist as the unit of visual working memory.

tRNA-derived fragments: Unveiling new roles and molecular mechanisms in cancer progression.

tRNA-derived fragments (tRFs) are novel small noncoding RNAs (sncRNAs) that range from approximately 14 to 50 nt. They are generated by the cleavage of mature tRNAs or precursor tRNAs (pre-tRNAs) at specific sites. Based on their origin and length, tRFs can be classified into three categories: (1) tRF-1 s; (2) tRF-3 s, tRF-5 s, and internal tRFs (i-tRFs); and (3) tRNA halves. They play important roles in stress response, signal transduction, and gene expression processes. Recent studies have identified differential expression of tRFs in various tumors. Aberrantly expressed tRFs have critical clinical value and show promise as new biomarkers for tumor diagnosis and prognosis and as therapeutic targets. tRFs regulate the malignant progression of tumors via various mechanisms, primarily including modulation of noncoding RNA biogenesis, global chromatin organization, gene expression regulation, modulation of protein translation, regulation of epigenetic modification, and alternative splicing regulation. In conclusion, tRF-mediated regulatory pathways could present new avenues for tumor treatment, and tRFs could serve as promising therapeutic targets for cancer therapy.

CD147 regulates the formation and function of immune synapses.

CD147 is a T cell activation-associated molecule which is closely involved in the formation of the immune synapse (IS). However, the precise role of CD147 in T cell activation and IS formation remains unclear. In the present study, we demonstrated that CD147 translocated to the IS upon T cell activation and was primarily distributed in the peripheral super molecular cluster (p-SMAC). The knock down of CD147 expression in T cells, but not in B cells, impaired IS formation. CD147 participated in IS formation between T cells and different types of antigen-presenting cells (APCs), including macrophages and dendritic cells. Ligation of CD147 with its monoclonal antibody (mAb) HAb18 effectively inhibited T cell activation and IL-2 secretion. CD98, a critical molecule interacting with CD147, was distributed in IS in a CD147-dependent way. Phosphorylation levels of T cell receptor (TCR) related molecules, like ZAP-70, ERK, and cJun, were down-regulated by CD147 ligation, which is crucial for the interaction of CD147 and TCR signaling transduction. CD147 is indispensable for the formation of immune synapses and plays an important role in the regulation of its function.

A promoter-RBS library for fine-tuning gene expression in Methanosarcina acetivorans.

Methanogens are the main biological producers of methane on Earth. Methanosarcina acetivorans is one of the best characterized methanogens that has powerful genetic tools for genome editing. To study the physiology of this methanogen in further detail as well as to effectively balance the flux of their engineered metabolic pathways in expansive project undertakings, there is the need for controlled gene expression, which then requires the availability of well-characterized promoters and ribosome-binding sites (RBS). In this study, we constructed a library of 33 promoter-RBS combinations that includes 13 wild-type and 14 hybrid combinations, as well as six combination variants in which the 5'-untranslated region (5'UTR) was rationally engineered. The expression strength for each combination was calculated by inducing the expression of the ß-glucuronidase reporter gene in M. acetivorans cells in the presence of the two most used growth substrates, either methanol (MeOH) or trimethyl amine (TMA). In this study, the constructed library covers a relatively wide range (140-fold) between the weakest and strongest promoter-RBS combination as well as shows a steady increase and allows different levels of gene expression. Effects on the gene expression strength were also assessed by making measurements at three distinct growth phases for all 33 promoter-RBS combinations. Our promoter-RBS library is effective in enabling the fine-tuning of gene expression in M. acetivorans for physiological studies and the design of metabolic engineering projects that, e.g., aim for the biotechnological valorization of one-carbon compounds. IMPORTANCE: Methanogenic archaea are potent producers of the greenhouse gas methane and thus contribute substantially to global warming. Under controlled conditions, these microbes can catalyze the production of biogas, which is a renewable fuel, and might help counter global warming and its effects. Engineering the primary metabolism of Methanosarcina acetivorans to render it better and more useful requires controllable gene expression, yet only a few well-characterized promoters and RBSs are presently available. Our study rectifies this situation by providing a library of 33 different promoter-RBS combinations with a 140-fold dynamic range in expression strength. Future metabolic engineering projects can take advantage of this library by using these promoter-RBS combinations as an efficient and tunable gene expression system for M. acetivorans. Furthermore, the methodologies we developed in this study could also be utilized to construct promoter libraries for other types of methanogens.

Experimental demonstration on 400†nm-scale bandwidth optical parametric chirped-pulse amplification based on mixed cascaded crystals.

We present an optical parametric chirped-pulse amplification (OPCPA) based on mixed cascaded crystals, taking advantage of the unique parametric phase-matching of lithium triborate (LiB3O5, LBO) and yttrium calcium oxyborate ((YCa4O(BO3)3, YCOB) crystals. The OPCPA properties of LBO at 880 nm and YCOB at 750 nm are studied respectively. After amplification by two LBO and two YCOB crystals, a total signal gain of 108 and spectral bandwidth close to 400 nm is obtained. After accurate dispersion compensation with a grating-pair compressor and chirped mirror compensator, a pulse duration of 9.4 fs is obtained by a SHG-frequency-resolved optical grating (FROG). This approach will be of great significance in high energy amplifier for high peak power few-cycle laser sources.

IAIH-PG consensus for histological criteria of AIH: Multicentre validation with focus on chronic liver diseases in China.

BACKGROUND AND AIMS: The International AIH Pathology Group (IAIH-PG) put forward the new histological criteria of autoimmune hepatitis (AIH) in 2022, which have not undergone adequate verification. In this study, we verified the applicability of the new histological criteria in the population of Chinese patients with chronic liver disease, comparing it with the simplified criteria. METHODS: The gold standard for diagnosis in all patients was based on histological findings, combined with clinical manifestations and laboratory tests and determined after a follow-up period of at least 3 years. A total of 640 patients with various chronic liver diseases from multiple centres underwent scoring using the new histological criteria and the simplified criteria, comparing their diagnostic performance. RESULTS: In this study, the new histological criteria showed a sensitivity of 73.6% and 100% for likely and possible AIH, with specificities of 100% and 69.0% respectively. The coincidence rates of possible AIH for the new histological criteria, simplified histological criteria and simplified score were 81.7%, 72.8% and 69.7% respectively. For likely AIH, the rates were 89.2%, 75.9% and 65.6% respectively. Based on the new histological criteria, all patients with AIH were correctly diagnosed. Specifically, 73.6% were diagnosed with likely AIH and 26.4% were possible AIH. Additionally, the simplified histological criteria achieved a diagnosis rate of 98.6% for AIH, while the simplified score could only diagnose 53.8% of AIH. CONCLUSIONS: Compared with the simplified score and simplified histological criteria, the sensitivity and specificity of the new histological criteria for AIH were significantly improved. The results indicate that the new histological criteria exhibit high sensitivity and specificity for diagnosing AIH in China.

The detrimental effect of biopsy preceding resection in surgically accessible glioblastoma: results from the national cancer database.

PURPOSE: Aggressive resection in surgically-accessible glioblastoma (GBM) correlates with improved survival over less extensive resections. However, the clinical impact of performing a biopsy before definitive resection have not been previously evaluated. METHODS: We analyzed 17,334 GBM patients from the NCDB from 2010-2014. We categorized them into: "upfront resection" and "biopsy followed by resection". The outcomes of interes included OS, 30-day readmission/mortality, 90-day mortality, and length of hospital stay (LOS). The Kaplan-Meier methods and accelerated failure time (AFT) models were applied for survival analysis. Multivariable binary logistic regression were performed to compare differences among groups. Multiple imputation and propensity score matching (PSM) were conducted for validation. RESULTS: "Upfront resection" had superior OS over "biopsy followed by resection" (median OS:12.4 versus 11.1 months, log-rank p = 0.001). Similarly, multivariable AFT models favored "upfront resection" (time ratio[TR]:0.83, 95%CI: 0.75-0.93, p = 0.001). Patients undergoing "upfront gross-total resection (GTR)" had higher OS over "upfront subtotal resection (STR)", "GTR following STR", and "GTR or STR following initial biopsy" (14.4 vs. 10.3, 13.5, 13.3, and 9.1 months;TR: 1.00 [Ref.], 0.75, 0.82, 0.88, and 0.67). Recent years of diagnosis, higher income, facilities located in Southern regions, and treatment at academic facilities were significantly associated with the higher likelihood of undergoing upfront resection. Multivariable regression showed a decreased 30 and 90-day mortality for patients undergoing "upfront resection", 73% and 44%, respectively (p < 0.001). CONCLUSIONS: Pre-operative biopsies for surgically accessible GBM are associated with worse survival despite subsequent resection compared to patients undergoing upfront resection.

A positive association between BMI and kidney stones among the diabetic population: a cross-sectional study from NHANES.

BACKGROUND: In the past, research has shown that a higher body mass index (BMI) is one of the variables that increase the likelihood of kidney stones; however, no studies have found a connection between the two in the type II diabetic population. The purpose of this research is to reveal the association between BMI and kidney stones in the type II diabetic population. METHODS: We selected demographic data, laboratory data, lifestyle, and medical history from the NHANES. Specifically includes age, gender, systemic immune-inflammation index (SII), poverty income rate (PIR), body mass index (BMI), kidney stones, education, coronary artery disease, smoking, and drinking. RESULTS: BMI and kidney stones were shown to have a positive association in type II diabetics (blood sugar level > 7.0 mmol/L or diagnosed by a doctor) (OR = 1.021, 95% CI 1.008-1.033, P = 0.001), even after controlling for factors, such as age, gender, race, education level, coronary heart disease, smoking, and drinking. The subgroup analysis revealed a more significant positive association among the 67-80 years, female and Non-Hispanic White population. CONCLUSIONS: There is a positive correlation between BMI and kidney stones among the type II diabetic population.

Effectiveness of Global Leadership Initiative on Malnutrition and Subjective Global Assessment for diagnosing malnutrition and predicting wound healing in patients with diabetic foot ulcers.

Malnutrition significantly hampers wound healing processes. This study aimed to compare the effectiveness of the Global Leadership Initiative on Malnutrition (GLIM) and Subjective Global Assessment (SGA) in diagnosing malnutrition and predicting wound healing in patients with diabetic foot ulcers (DFU). GLIM criteria were evaluated for sensitivity (SE), specificity (SP), positive predictive value, negative predictive value and kappa (κ) against SGA as the reference. Modified Poisson regression model and the DeLong test investigated the association between malnutrition and non-healing ulcers over 6 months. This retrospective cohort study included 398 patients with DFU, with a mean age of 66·3 ± 11·9 years. According to SGA and GLIM criteria, malnutrition rates were 50·8 % and 42·7 %, respectively. GLIM criteria showed a SE of 67·3 % (95 % CI 60·4 %, 73·7 %) and SP of 82·7 % (95 % CI 76·6 %, 87·7 %) in identifying malnutrition, with a positive predictive value of 80·0 % and a negative predictive value of 71·1 % (κ = 0·50) compared with SGA. Multivariate analysis demonstrated that malnutrition, as assessed by SGA, was an independent risk factor for non-healing (relative risk (RR) 1·84, 95 % CI 1·45, 2·34), whereas GLIM criteria were associated with poorer ulcer healing in patients with estimated glomerular filtration rate ≥ 60 ml/min/1·73m2 (RR: 1·46, 95 % CI 1·10, 1·94). SGA demonstrated a superior area under the receiver's operating characteristic curve for predicting non-healing compared with GLIM criteria (0·70 (0·65-0·75) v. 0·63 (0·58-0·65), P < 0·01). These findings suggest that both nutritional assessment tools effectively identify patients with DFU at increased risk, with SGA showing superior performance in predicting non-healing ulcers.

Analysis of risk factors associated with diffuse alveolar haemorrhage in patients with ANCA-associated vasculitis and construction of a risk prediction model using line graph.

OBJECTIVES: This study aims to analyse the risk factors associated with diffuse alveolar haemorrhage (DAH) in patients with ANCA-associated vasculitis (AAV) and construct a risk prediction model using line graph. METHODS: A retrospective study was conducted from January 2012 to May 2023 at the First Clinical College of Three Gorges University, focusing on patients diagnosed with AAV. Clinical and laboratory data were collected from these patients. The potential predictors subsets of high-risk AAV combined with DAH were screened by LASSO regression and 10-fold cross-validation method, and determined by using multivariate Logistic regression analysis, then were used for developing a prediction nomogram for high-risk AAV combined with DAH using the R software. ROC curve analysis was used to validate the model's stability. Internal validation was performed using a bootstrap method. The discrimination of the nomogram was determined by calculating the average consistency index(C-index). The calibration curve was used to assess the calibration of the nomogram. RESULTS: A total of 234 patients with AAV were included, among whom 85 developed DAH, with an incidence rate of 36%, and the average age was 63±12. Multivariable logistic regression analysis showed that Age [OR=1.037 (95%CI: 1.006, 1.071), p=0.019], platelet count (PLT) [OR=0.996 (95%CI: 0.992, 0.999), p=0.029], ESR [OR=1.028 (95%CI: 1.015, 1.042), p<0.01], HB [OR=0.978 (95%CI: 0.959, 0.996), p=0.024], and haematuria [OR=3.77 (95%CI: 1.677, 8.976), p=0.001] were found to be independent predictors of AAV combined with DAH and were used to construct a nomogram. The AUCROC values of the nomogram for DAH in AAV patients was 0.852 (95%CI: 0.801, 0.903), and the C-index could reach 0.824 after internal verification, showing good differentiation and consistency. CONCLUSIONS: The new nomogram, which included age, Hb, ESR, PLT and haematuria as variables, had the potential to predict the risk of AAV patients complicated with DAH.

Immunization with a peptide mimicking lipoteichoic acid induces memory B cells in BALB/c mice.

BACKGROUND: There is an urgent clinical need for developing novel immunoprophylaxis and immunotherapy strategies against Staphylococcus aureus (S. aureus). In our previous work, immunization with a tetra-branched multiple antigenic peptide, named MAP2-3 that mimics lipoteichoic acid, a cell wall component of S. aureus, successfully induced a humoral immune response and protected BALB/c mice against S. aureus systemic infection. In this study, we further investigated whether vaccination with MAP2-3 can elicit immunologic memory. METHODS: BALB/c mice were immunized with MAP2-3 five times. After one month of the last vaccination, mice were challenged with heat-killed S. aureus via intraperitoneal injection. After a 7-day inoculation, the percentage of plasma cells, memory B cells, effector memory T cells, and follicular helper T cells were detected by flow cytometry. The levels of IL-6, IL-21, IL-2, and IFN-γ were measured by real-time PCR and ELISA. Flow cytometry results were compared by using one-way ANOVA or Mann-Whitney test, real-time PCR results were compared by using one-way ANOVA, and ELISA results were compared by using one-way ANOVA or student's t-test. RESULTS: The percentage of plasma cells and memory B cells in the spleen and bone marrow from the MAP2-3 immunized mice was significantly higher than that from the control mice. The percentage of effector memory T cells in spleens and lymphoid nodes as well as follicular helper T cells in spleens from the MAP2-3 immunized mice were also higher. Moreover, the levels of IL-6 and IL-21, two critical cytokines for the development of memory B cells, were significantly higher in the isolated splenocytes from immunized mice after lipoteichoic acid stimulation. CONCLUSIONS: Immunization with MAP2-3 can efficiently induce memory B cells and memory T cells.

Synthesis and biological evaluation of triazolones/oxadiazolones as novel urease inhibitors.

Urease is the main virulence factor of infectious gastritis and gastric ulcers. Urease inhibitors are regarded as the first choice for the treatment of such diseases. Based on the triazolone/oxadiazolone skeleton, a urea-like fragment being able to specifically bind the urease activity pocket and prevent urea from hydrolysis, we designed and synthesized 45 triazolones/oxadiazolones as urease inhibitors. Eight compounds were proved to show excellent inhibitory activity against Helicobacter pylori urease, being more potency than the clinically used urease inhibitor acetohydroxamic acid. The most active inhibitor with IC50 value of 1.2 µM was over 20-fold higher potent than the positive control. Enzymatic kinetic assays showed that these novel inhibitors reversibly inhibited urease with a mixed competitive mechanism. Molecular dockings provided evidence for the observations in enzyme assays. Furthermore, these novel inhibitors were proved as drug-like compounds with very low cytotoxicity to mammalian cells and favorable water solubility. These results suggested that triazolone and oxadiazolone were promising scaffolds for the design and discovery of novel urease inhibitors, and were expected as good candidates for further drug development.

Association of neutrophil-lymphocyte ratio with all-cause and cardiovascular mortality in US adults with diabetes and prediabetes: a prospective cohort study.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) is a novel hematological parameter to assess systemic inflammation. Prior investigations have indicated that an increased NLR may serve as a potential marker for pathological states such as cancer and atherosclerosis. However, there exists a dearth of research investigating the correlation between NLR levels and mortality in individuals with diabetes and prediabetes. Consequently, this study aims to examine the connection between NLR and all-cause as well as cardiovascular mortality in the population of the United States (US) with hyperglycemia status. METHODS: Data were collected from a total of 20,270 eligible individuals enrolled for analysis, spanning ten cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. The subjects were categorized into three groups based on tertiles of NLR levels. The association of NLR with both all-cause and cardiovascular mortality was evaluated using Kaplan-Meier curves and Cox proportional hazards regression models. Restricted cubic splines were used to visualize the nonlinear relationship between NLR levels and all-cause and cardiovascular mortality in subjects with diabetes after accounting for all relevant factors. RESULTS: Over a median follow-up period of 8.6 years, a total of 1909 subjects with diabetes died, with 671 deaths attributed to cardiovascular disease (CVD). And over a period of 8.46 years, 1974 subjects with prediabetes died, with 616 cases due to CVD. The multivariable-adjusted hazard ratios (HRs) comparing high to low tertile of NLR in diabetes subjects were found to be 1.37 (95% CI, 1.19-1.58) for all-cause mortality and 1.63 (95% CI, 1.29-2.05) for CVD mortality. And the correlation between high to low NLR tertile and heightened susceptibility to mortality from any cause (HR, 1.21; 95% CI, 1.03-1.43) and CVD mortality (HR, 1.49; 95% CI, 1.08-2.04) remained statistically significant (both p-values for trend < 0.05) in prediabetes subjects. The 10-year cumulative survival probability was determined to be 70.34%, 84.65% for all-cause events, and 86.21%, 94.54% for cardiovascular events in top NLR tertile of diabetes and prediabetes individuals, respectively. Furthermore, each incremental unit in the absolute value of NLR was associated with a 16%, 12% increase in all-cause mortality and a 25%, 24% increase in cardiovascular mortality among diabetes and prediabetes individuals, respectively. CONCLUSIONS: The findings of this prospective cohort study conducted in the US indicate a positive association of elevated NLR levels with heightened risks of overall and cardiovascular mortality among adults with diabetes and prediabetes. However, potential confounding factors for NLR and the challenge of monitoring NLR's fluctuations over time should be further focused.

Family intimacy and adaptability and non-suicidal self-injury: a mediation analysis.

BACKGROUND: Current research has been focusing on non-suicidal self-injury (NSSI) behaviors among adolescents with depression. Although family intimacy and adaptability are considered protective factors for NSSI, evidence supporting this relationship is lacking. OBJECTIVE: This study aims to examine the mechanisms operating in the relationship between family intimacy and adaptability and NSSI behaviors among adolescents. METHODS: A self-administered general demographic information questionnaire, the Behavioral Functional Assessment Scale for Non-Suicidal Self-Injury, the Family Intimacy and Adaptability Scale, the Connor-Davidson Resilience Scale, and the Self-Assessment of Depression Scale were distributed among adolescents with depression in three tertiary hospitals in Jiangsu Province. RESULTS: The relationship between family intimacy and adaptability and NSSI was assessed among 596 adolescents with depression. The results revealed the following: (1) Family intimacy and adaptability were negatively correlated with NSSI behavior. (2) Psychological resilience and depression levels acted as chain mediators in the relationship between family intimacy and adaptability and NSSI behavior. CONCLUSIONS: Enhancing psychological resilience, controlling depressive symptoms, and reducing depression severity among adolescents by improving their family intimacy and adaptability are conducive to preventing and mitigating their NSSI behaviors.

Improved optimization for the neural-network quantum states and tests on the chromium dimer.

The advent of Neural-network Quantum States (NQS) has significantly advanced wave function ansatz research, sparking a resurgence in orbital space variational Monte Carlo (VMC) exploration. This work introduces three algorithmic enhancements to reduce computational demands of VMC optimization using NQS: an adaptive learning rate algorithm, constrained optimization, and block optimization. We evaluate the refined algorithm on complex multireference bond stretches of H2O and N2 within the cc-pVDZ basis set and calculate the ground-state energy of the strongly correlated chromium dimer (Cr2) in the Ahlrichs SV basis set. Our results achieve superior accuracy compared to coupled cluster theory at a relatively modest CPU cost. This work demonstrates how to enhance optimization efficiency and robustness using these strategies, opening a new path to optimize large-scale restricted Boltzmann machine-based NQS more effectively and marking a substantial advancement in NQS's practical quantum chemistry applications.

Associations between non-insulin-based insulin resistance indices and heart failure prevalence in overweight/obesity adults without diabetes mellitus: evidence from the NHANES 2001-2018.

BACKGROUND: The triglyceride glucose (TyG) index and triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio are recognized as simple non-insulin-based insulin resistance indices. Our study aimed to explore the relationship between these two indicators and heart failure (HF) in overweight or obesity individuals without diabetes. METHODS: This cross-sectional study selected 13,473 participants from the National Health and Nutrition Examination Survey (NHANES) 2001-2018 dataset. Weighted multivariable logistic regression and subgroup analysis were employed to evaluate the relationships between TyG index, TG/HDL-C ratio, and HF prevalence, respectively. Additionally, smooth curve fitting was utilized to analyze the dose-response relationships. RESULTS: A total of 13,473 obesity or overweight people without diabetes were included in this study through screening, among whom 291 (2.16%) had comorbid HF. The results of multivariable logistic regression suggested that the highest TyG index (OR = 2.4, 95% CI = 1.4-4.2, p = 0.002) and the highest TG/HDL-C ratio (OR = 1.2, 95% CI = 1.1-1.3, p < 0.001) both increased the prevalence of HF, especially in the non-Hispanic population. Dose-response relationships suggested nonlinear relationships between these two indicators and HF. CONCLUSION: Our study demonstrated that elevated TyG index and TG/HDL-C ratio were closely associated with the prevalence of HF, and both exhibited nonlinear relationships with HF prevalence in overweight/obesity adults without diabetes. Based on these findings, additional prospective studies are needed for further validation.

Perioperative, functional, and oncological outcomes after cryoablation or partial nephrectomy for small renal masses in solitary kidneys: a systematic review and meta-analysis.

AIM: This study aims to compare the perioperative, functional, and oncological outcomes of cryoablation (CA) and partial nephrectomy (PN) for managing small renal masses in patients with solitary kidneys. The study seeks to assess the efficacy and safety of both interventions, evaluating their impact on kidney function and their ability to mitigate cancer recurrence. METHODS: Searches were systematically conducted on PubMed, Scopus, EMBASE, SinoMed, and Google Scholar, identifying seven observational studies. Statistical analysis was performed using Stata v.12.0 and Review Manager version 5.2. Results for dichotomous variables are expressed using odds ratios, and weighted mean differences are used for continuous variables. RESULTS: Our findings revealed that patients undergoing CA experienced significantly shorter operative time (p < 0.0001), reduced estimated blood loss (p < 0.00001), a shorter length of stay (p = 0.0001), and fewer postoperative complications (p = 0.02) compared to those undergoing PN. Although the CA group exhibited a lower transfusion rate (p = 0.69) compared with the PN group, the difference was not statistically significant. The combined data analysis demonstrated a significantly lower increase in serum creatinine levels after surgery in the CA group compared with the PN group (p = 0.003). Similarly, there was a noteworthy decrease in the estimated glomerular filtration rate after surgery in the PN group compared with the CA group (p < 0.0001). While not statistically significant, the CA group showed a lower postoperative dialysis rate (p = 0.11). Regarding oncological outcomes, the analysis revealed no significant differences between CA and PN concerning local recurrence (p = 0.2) and distant metastasis (p = 0.12), respectively. CONCLUSIONS: Our analysis indicates comparable efficacy between PN and CA in controlling tumour recurrence and metastasis. However, CA is associated with superior preservation of renal function, significantly enhanced perioperative outcomes, and fewer postoperative complications. Based on our data, it can be inferred that the scope for applying CA might be expanded to encompass more patients seeking a less invasive treatment option.