Identification and validation of mutual hub genes in idiopathic pulmonary fibrosis and rheumatoid arthritis-associated usual interstitial pneumonia.

Objectives: The study aims at exploring common hub genes and pathways in idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis-associated usual interstitial pneumonia (RA-UIP) through integrated bioinformatics analyses. Methods: The GSE199152 dataset containing lung tissue samples from IPF and RA-UIP patients was acquired from the Gene Expression Omnibus (GEO) database. The identification of overlapping differentially expressed genes (DEGs) in IPF and RA-UIP was carried out through R language. Protein-protein interaction (PPI) network analysis and module analysis were applied to filter mutual hub genes in the two diseases. Enrichment analyses were also conducted to analyze the possible biological functions and pathways of the overlapped DEGs and hub genes. The diagnostic value of key genes was assessed with R language, and the expressions of these genes in pulmonary cells of IPF and rheumatoid arthritis-associated interstitial lung disease (RA-ILD) patients were analyzed with single cell RNA-sequencing (scRNA-seq) datasets. The expression levels of hub genes were validated in blood samples from patients, specimens of human lung fibroblasts, lung tissue samples from mice, as well as external GEO datasets. Results: Four common hub genes (THBS2, TIMP1, POSTN, and CD19) were screened. Enrichment analyses showed that the abnormal expressions of DEGs and hub genes may be connected with the onset of IPF and RA-UIP by regulating the progression of fibrosis. ScRNA-seq analyses illustrated that for both IPF and RA-ILD patients, THBS2, TIMP1, and POSTN were mainly expressed in lung fibroblasts, while CD19 was uniquely high-expressed in B cells. The qRT-PCR and immunohistochemistry (IHC) results verified that the expression levels of hub genes were mostly in accordance with the findings obtained from the bioinformatics analyses. Conclusion: Though IPF and RA-UIP are distinct diseases, they may to some extent have mutual pathogenesis in the development of fibrosis. THBS2, TIMP1, POSTN, and CD19 may be the potential biomarkers of IPF and RA-UIP, and intervention on related pathways of these genes could offer new strategies for the precision treatment of IPF and RA-UIP.

The purinergic receptor P2X3 promotes facial pain by activating neurons and cytokines in the trigeminal ganglion.

The mechanism underlying allodynia/hyperalgesia caused by dental pulpitis has remained enigmatic. This investigation endeavored to characterize the influence of the purinergic receptor P2X3 on pain caused by experimental pulpitis and the mechanism involved. An experimental model of irreversible pulpitis was produced by the drilling and exposure of the dental pulp of the left upper first and second molars in rats, followed by measuring nociceptive responses in the oral and maxillofacial regions. Subsequently, neuronal activity and the expression of P2X3 and pertinent cytokines in the trigeminal ganglion (TG) were meticulously examined and analyzed. Histological evidence corroborated that significant pulpitis was produced in this model, which led to a distinct escalation in nociceptive responses in rats. The activation of neurons, coupled with the upregulated expression of c-fos, P2X3, p-p38, TNF-α and IL-1ß, was identified subsequent to the pulpitis surgery within the TG. The selective inhibition of P2X3 with A-317491 effectively restrained the abnormal allodynia/hyperalgesia following the pulpitis surgery and concurrently inhibited the upregulation of p-p38, TNF-α and IL-1ß within the TG. These findings suggest that the P2X3 signaling pathway plays a pivotal role in instigating and perpetuating pain subsequent to the induction of pulpitis in rats, implicating its association with the p38 MAPK signaling pathway and inflammatory factors.

Proteomics-based Model for Predicting the Risk of Brain Metastasis in Patients with Resected Lung Adenocarcinoma carrying the EGFR Mutation.

Introduction: Epidermal growth factor receptor (EGFR) mutation is common in Chinese patients with lung adenocarcinoma (LUAD). Brain metastases (BMs) is high and associated with poor prognosis. Identification of EGFR-mutant patients at high risk of developing BMs is important to reduce or delay the incidence of BMs. Currently, there is no literature on the prediction and modeling of EGFR brain metastasis at the proteinomics level. Methods: We conducted a retrospective study of BMs in postoperative recurrent LUAD with EGFR mutation in the First Affiliated Hospital of Guangzhou Medical University. Tissue proteomic analysis was applied in the primary tumors of resected LUAD in this study using liquid chromatography-mass spectrometry (LC-MS/MS). To identify potential markers for predicting LUAD BM, comparative analyses were performed on different groups to evaluate proteins associated with high risk of BMs. Results: A combination of three potential marker proteins was found to discriminate well between distal metastasis (DM) and local recurrence (LR) of postoperative LUAD with EGFR mutation. Gene Ontology (GO) analysis of significantly altered proteins between BM and non-BM (NBM) indicated that lipid metabolism and cell cycle-related pathways were involved in BMs of LUAD. And the enriched pathways correlated with BMs were found to be quite different in the comparison groups of postoperative adjuvant therapy, tyrosine kinase inhibitor (TKI), and chemotherapy groups. Finally, we developed a random forest algorithm model with eight proteins (RRS1, CPT1A, DNM1, SRCAP, MLYCD, PCID2, IMPAD1 and FILIP1), which showed excellent predictive value (AUC: 0.9401) of BM in patients with LUAD harboring EGFR mutation. Conclusions: A predictive model based on protein markers was developed to accurately predict postoperative BM in operable LUAD harboring EGFR mutation.

Comparative transcriptomic analysis reveals the molecular mechanism underlying seedling heterosis and its relationship with hybrid contemporary seeds DNA methylation in soybean.

Heterosis is widely used in crop production, but phenotypic dominance and its underlying causes in soybeans, a significant grain and oil crop, remain a crucial yet unexplored issue. Here, the phenotypes and transcriptome profiles of three inbred lines and their resulting F1 seedlings were analyzed. The results suggest that F1 seedlings with superior heterosis in leaf size and biomass exhibited a more extensive recompilation in their transcriptional network and activated a greater number of genes compared to the parental lines. Furthermore, the transcriptional reprogramming observed in the four hybrid combinations was primarily non-additive, with dominant effects being more prevalent. Enrichment analysis of sets of differentially expressed genes, coupled with a weighted gene co-expression network analysis, has shown that the emergence of heterosis in seedlings can be attributed to genes related to circadian rhythms, photosynthesis, and starch synthesis. In addition, we combined DNA methylation data from previous immature seeds and observed similar recompilation patterns between DNA methylation and gene expression. We also found significant correlations between methylation levels of gene region and gene expression levels, as well as the discovery of 12 hub genes that shared or conflicted with their remodeling patterns. This suggests that DNA methylation in contemporary hybrid seeds have an impact on both the F1 seedling phenotype and gene expression to some extent. In conclusion, our study provides valuable insights into the molecular mechanisms of heterosis in soybean seedlings and its practical implications for selecting superior soybean varieties.

A deep learning model, NAFNet, predicts adverse pathology and recurrence in prostate cancer using MRIs.

We aimed to apply a potent deep learning network, NAFNet, to predict adverse pathology events and biochemical recurrence-free survival (bRFS) based on pre-treatment MRI imaging. 514 prostate cancer patients from six tertiary hospitals throughout China from 2017 and 2021 were included. A total of 367 patients from Fudan University Shanghai Cancer Center with whole-mount histopathology of radical prostatectomy specimens were assigned to the internal set, and cancer lesions were delineated with whole-mount pathology as the reference. The external test set included 147 patients with BCR data from five other institutes. The prediction model (NAFNet-classifier) and integrated nomogram (DL-nomogram) were constructed based on NAFNet. We then compared DL-nomogram with radiology score (PI-RADS), and clinical score (Cancer of the Prostate Risk Assessment score (CAPRA)). After training and validation in the internal set, ROC curves in the external test set showed that NAFNet-classifier alone outperformed ResNet50 in predicting adverse pathology. The DL-nomogram, including the NAFNet-classifier, clinical T stage and biopsy results, showed the highest AUC (0.915, 95% CI: 0.871-0.959) and accuracy (0.850) compared with the PI-RADS and CAPRA scores. Additionally, the DL-nomogram outperformed the CAPRA score with a higher C-index (0.732, P < 0.001) in predicting bRFS. Based on this newly-developed deep learning network, NAFNet, our DL-nomogram could accurately predict adverse pathology and poor prognosis, providing a potential AI tools in medical imaging risk stratification.

Multi-integrated approach for unraveling small open reading frames potentially associated with secondary metabolism in Streptomyces.

IMPORTANCE: Due to their small size and special chemical features, small open reading frame (smORF)-encoding peptides (SEPs) are often neglected. However, they may play critical roles in regulating gene expression, enzyme activity, and metabolite production. Studies on bacterial microproteins have mainly focused on pathogenic bacteria, which are importance to systematically investigate SEPs in streptomycetes and are rich sources of bioactive secondary metabolites. Our study is the first to perform a global identification of smORFs in streptomycetes. We established a peptidogenomic workflow for non-model microbial strains and identified multiple novel smORFs that are potentially linked to secondary metabolism in streptomycetes. Our multi-integrated approach in this study is meaningful to improve the quality and quantity of the detected smORFs. Ultimately, the workflow we established could be extended to other organisms and would benefit the genome mining of microproteins with critical functions for regulation and engineering useful microorganisms.

Development Trend in Composition Optimization, Microstructure Manipulation, and Strengthening Methods of Die Steels under Lightweight and Integrated Die Casting.

In the general environment of lightweight automobiles, the integrated die-casting technology proposed by Tesla has become the general mode to better achieve weight reduction in automobiles. The die-casting mold required by integrated die-casting technology has the characteristics of large scale and complexity. Hence, higher requirements are put forward for the comprehensive performance of the die steel. Despite the stagnation in the progress of conventional strengthening methods, enhancing the performance of die steel has become increasingly challenging. Indeed, it necessitates exploring novel die steel and optimizing heat treatment and reinforcement technologies. This article summarizes and analyzes the development status of die steel and corresponding heat treatment and microstructure manipulation as well as strengthening methods and elaborates on an excellent nano-strengthening technology. Furthermore, this review will aid researchers in establishing a comprehensive understanding of the development status of die steel and the processes utilized for its strengthening. It will also assist them in developing die steel with improved comprehensive performance to meet the high demand for mold steel in the integrated die-casting technology of the new era.

Effect of 1 H-NMR serum lipoproteins on immunotherapy response in advanced triple-negative breast cancer patients.

We previously reported the results of a phase II trial of anti-PD-1 antibody plus anti-vascular endothelial growth factor receptor 2 inhibitors and eribulin in heavily pretreated advanced triple-negative breast cancer with a favorable objective response rate (ORR) of 37.0% (NCT04303741). Here we report updated survival outcomes and serum metabolite changes of the study. Proton nuclear magnetic resonance spectroscopy was used to detect metabolite dynamics and explore biomarkers for response. We found that treatment-sensitive patients had higher very low-density lipoprotein-related metabolite expression at baseline. A lipid proteomics model consisting of six metabolites predicted ORR and progression-free survival at 6 months with area under the receiver operating characteristic curves of 0.88 and 0.87, respectively. Serum asparagine and sarcosine concentrations were significantly higher after treatment in treatment-resistant patients. In conclusion, we constructed a model consisting of six metabolites to identify patients who benefit more from the triplet treatment, and asparagine and sarcosine may be associated with treatment resistance.

Skeletal Editing of Dibenzolactones to Fluorenes via Ni- or Pd-Catalyzed Decarboxylation.

The skeletal editing of dibenzolactones to fluorenes by Ni- or Pd-catalyzed decarboxylation is reported. In contrast to previously reported intramolecular decarboxylative couplings, inductively electron-withdrawing ortho substituents on the aryl carboxylate moiety and metal additives are not required. The decarboxylation reaction proceeds cleanly and can be applied to the skeletal editing of a natural product analogue. Mechanistic observations are consistent with stabilization of the carboxylate-ligated Ni complex over the Ni-carboxylate ion pair, which is the key factor in promoting the challenging decarboxylation step in the catalytic cycle.

Comprehensive and deep profiling of the plasma proteome with protein corona on zeolite NaY.

Proteomic characterization of plasma is critical for the development of novel pharmacodynamic biomarkers. However, the vast dynamic range renders the profiling of proteomes extremely challenging. Here, we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY. Specifically, zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY (NaY-PPC), followed by conventional protein identification using liquid chromatography-tandem mass spectrometry. NaY was able to significantly enhance the detection of low-abundance plasma proteins, minimizing the "masking" effect caused by high-abundance proteins. The relative abundance of middle- and low-abundance proteins increased substantially from 2.54% to 54.41%, and the top 20 high-abundance proteins decreased from 83.63% to 25.77%. Notably, our method can quantify approximately 4000 plasma proteins with sensitivity up to pg/mL, compared to only about 600 proteins identified from untreated plasma samples. A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states. In summary, this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.

Automatic Calcification Morphology and Distribution Classification for Breast Mammograms With Multi-Task Graph Convolutional Neural Network.

The morphology and distribution of microcalcifications are the most important descriptors for radiologists to diagnose breast cancer based on mammograms. However, it is very challenging and time-consuming for radiologists to characterize these descriptors manually, and there also lacks of effective and automatic solutions for this problem. We observed that the distribution and morphology descriptors are determined by the radiologists based on the spatial and visual relationships among calcifications. Thus, we hypothesize that this information can be effectively modelled by learning a relationship-aware representation using graph convolutional networks (GCNs). In this study, we propose a multi-task deep GCN method for automatic characterization of both the morphology and distribution of microcalcifications in mammograms. Our proposed method transforms morphology and distribution characterization into node and graph classification problem and learns the representations concurrently. We trained and validated the proposed method in an in-house dataset and public DDSM dataset with 195 and 583 cases,respectively. The proposed method reaches good and stable results with distribution AUC at 0.812 ± 0.043 and 0.873 ± 0.019, morphology AUC at 0.663 ± 0.016 and 0.700 ± 0.044 for both in-house and public datasets. In both datasets, our proposed method demonstrates statistically significant improvements compared to the baseline models. The performance improvements brought by our proposed multi-task mechanism can be attributed to the association between the distribution and morphology of calcifications in mammograms, which is interpretable using graphical visualizations and consistent with the definitions of descriptors in the standard BI-RADS guideline. In short, we explore, for the first time, the application of GCNs in microcalcification characterization that suggests the potential of using graph learning for more robust understanding of medical images.

O-GlcNAc transferase in astrocytes modulates depression-related stress susceptibility through glutamatergic synaptic transmission.

Major depressive disorder is a common and devastating psychiatric disease, and the prevalence and burden are substantially increasing worldwide. Multiple studies of depression patients have implicated glucose metabolic dysfunction in the pathophysiology of depression. However, the molecular mechanisms by which glucose and related metabolic pathways modulate depressive-like behaviors are largely uncharacterized. Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) is a glucose metabolite with pivotal functions as a donor molecule for O-GlcNAcylation. O-GlcNAc transferase (OGT), a key enzyme in protein O-GlcNAcylation, catalyzes protein posttranslational modification by O-GlcNAc and acts as a stress sensor. Here, we show that Ogt mRNA was increased in depression patients and that astroglial OGT expression was specifically upregulated in the medial prefrontal cortex (mPFC) of susceptible mice after chronic social-defeat stress. The selective deletion of astrocytic OGT resulted in antidepressant-like effects, and moreover, astrocytic OGT in the mPFC bidirectionally regulated vulnerability to social stress. Furthermore, OGT modulated glutamatergic synaptic transmission through O-GlcNAcylation of glutamate transporter-1 (GLT-1) in astrocytes. OGT astrocyte-specific knockout preserved the neuronal morphology atrophy and Ca2+ activity deficits caused by chronic stress and resulted in antidepressant effects. Our study reveals that astrocytic OGT in the mPFC regulates depressive-like behaviors through the O-GlcNAcylation of GLT-1 and could be a potential target for antidepressants.

Targeting CD38 to Suppress Osteoarthritis Development and Associated Pain After Joint Injury in Mice.

OBJECTIVE: This study was undertaken to determine the role of CD38, which can function as an enzyme to degrade NAD+ , in osteoarthritis (OA) development. METHODS: Human knee cartilage from normal donors and OA donors were examined for CD38 expression. "Gain-of-function," through overexpression of CD38 via transient transfection, and "loss-of-function," through pharmacologic inhibition of CD38, approaches were used to assess the effects of CD38 on intracellular NAD+ :NADH ratio and catabolic activity in chondrocytes. We also initiated joint injury-induced OA by surgical destabilization of the medial meniscus (DMM) in CD38 knockout mice and wild-type (WT; C57BL/6) mice and in WT male mice in the presence or absence of apigenin treatment. Cartilage degradation, synovial inflammation, subchondral bone changes, and pain behavior were evaluated after DMM surgery. We also examined expression of CD38 and the neuropeptide calcitonin gene-related peptide (CGRP) in knee sections from these mice. RESULTS: CD38 expression was up-regulated in human knee OA cartilage and in chondrocytes stimulated with the proinflammatory cytokine interleukin-1ß (IL-1ß). Overexpression of CD38 in chondrocytes resulted in reduced cellular NAD+ :NADH ratio and augmented catabolic responses to IL-1ß. These effects were reversed by pharmacologic inhibition of CD38. Cartilage degradation and synovial inflammation, associated with increased CD38 expression in cartilage and synovium, osteophyte formation and subchondral bone sclerosis, and pain-like behavior linked to increased CGRP expression in the synovium were observed in WT mice after joint injury. Such effects were significantly reduced in mice deficient in CD38 through either genetic knockout or pharmacologic inhibition. CONCLUSION: CD38 deficiency exerts OA disease-modifying effects. Inhibition of CD38 has the potential to be a novel therapeutic approach for OA treatment.

Early cholecystectomy following percutaneous transhepatic gallbladder drainage is effective for moderate to severe acute cholecystitis in the octogenarians.

BACKGROUND: Acute cholecystitis (AC) is a life-threatening infectious/inflammatory disease in older patients. This study aimed to investigate the safety and optimal timing of surgery in patients aged ≥ 80 years with moderate to severe AC who received percutaneous transhepatic gallbladder drainage (PTGBD). METHODS: From January 2008 to February 2021, 152 patients were retrospectively enrolled. Clinical outcomes were compared among patients who received laparoscopic cholecystectomy (LC), open cholecystectomy (OC), and conversion surgery, and between those who received early (< 6 weeks after PTGBD) and delayed cholecystectomy (≥ 6 weeks after PTGBD). Logistic regression analysis was used to identify risk factors for recurrent AC, further biliary events, conversion, and perioperative complications. RESULTS: Sixty-seven patients underwent LC, 62 underwent OC, and 23 underwent conversion surgery. Operation-related complications and mortality rates did not differ among the types of surgery; however, LC group had shorter operative time than the other groups. Eighty-two patients underwent early cholecystectomy, while 70 underwent delayed cholecystectomy. There were no differences in operative time, operation-related complications, and mortality rates between the groups. However, higher rates of recurrent AC and biliary events were observed in the delayed cholecystectomy group (52.9% vs. 4.9% and 57.1% vs. 8.5%, p < 0.001). On multivariate analysis, delayed cholecystectomy was a significant risk factor for recurrent AC (odds ratio [OR] = 19.42, p < 0.001) and further biliary events (OR = 15.95, p < 0.001). CONCLUSIONS: Early cholecystectomy is recommended for patients aged ≥ 80 years with moderate to severe AC following PTGBD.

Transitions in Frailty and 4-Year Mortality Risk in Taiwan Longitudinal Study on Aging.

OBJECTIVES: To explore the associations of (1) the frailty phenotype or frailty index transition with cause-specific mortality, and (2) different combinations of transition in frailty phenotype and frailty index with all-cause mortality. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Data from 3529 respondents aged >50 years who completed the 1999 and 2003 surveys of the Taiwan Longitudinal Study on Aging were analyzed. METHODS: Cox regression and subdistribution hazard models were constructed to investigate frailty phenotype or frailty index transitions (by categories of frailty phenotype, absolute and percentage changes in frailty index, and combined categories of the 2 measurements) and subsequent 4-year all-cause and cause-specific mortality, respectively. RESULTS: Among the frailty phenotype transition groups, the improved frailty group had overall mortality risk comparable to that of the maintained robustness/prefrailty group [hazard ratio (HR): 0.9; 95% CI: 0.7-1.2] and lower risk of mortality due to organ failure (HR: 0.4; 95% CI: 0.2-0.8; P = .015), whereas the worsened frailty group had the highest risk of all-cause mortality and death from infection, malignancy, cardiometabolic/cerebrovascular diseases, and other causes (HR: 1.8-3.7; all P < .03). The rapidly increased frailty index group had significantly higher all-cause and every cause-specific mortality than the decreased frailty index group (HR: 1.8-7.7; all P < .05). When frailty phenotype and frailty index transition groups were combined, participants with worsened frailty/rapidly increased frailty index had increased risk under the same frailty index/frailty phenotype transition condition, particularly for large changes in each factor (HR: 1.5-2.2; P < .01 for worsened frailty; 1.7-4.5, P < .03 for rapidly increased frailty index). CONCLUSIONS AND IMPLICATIONS: We found that considering both frailty phenotype and frailty index provided best mortality prediction. These associations were independent of baseline frailty status and comorbidities. Nevertheless, even capturing transitions in frailty phenotype or frailty index only can provide good mortality prediction, which supported adopting these approaches in different clinical settings.

Immunoglobulin Y Specific for SARS-CoV-2 Spike Protein Subunits Effectively Neutralizes SARS-CoV-2 Infectivity and Ameliorates Disease Manifestations In Vivo.

(Background) The coronavirus disease 2019 (COVID-19) that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carries high infectivity and mortality. Efficient intervention strategies are urgently needed. Avian immunoglobulin Y (IgY) showed efficacy against viral infection whereas the in vivo efficacy remains unclear. (Methods) We immunized laying hens with S1, S1 receptor-binding domain (S1-RBD), or S2 subunits of the SARS-CoV-2 spike (S) protein. After immunization, IgYs were collected and extracted from the egg yolks. The neutralization potential of IgYs was examined by the plaque reduction neutralization test (PRNT). The bioutility of IgYs was examined in Syrian hamsters in vivo. (Results) IgYs exhibited typical banding patterns in SDS-PAGE and Western blot and were immunoreactive against S1, S1-RBD, and S2 subunits. The plaque reduction neutralization test (PRNT) showed that all purified IgYs potently neutralized different SARS-CoV-2 strains in vitro. In Syrian hamsters, the combination of IgYs for S1-RBD and S2 subunits administered before or after SARS-CoV-2 infection effectively restored body weight loss and reduced intrapulmonary lesions and the amount of immunoreactive N protein-positive cells, which were caused by SARS-CoV-2 infection. (Conclusions) Collectively, IgYs specific for S protein subunits effectively neutralized SARS-CoV-2 in vitro and in vivo and may serve as prophylactic or therapeutic antibodies in the prevention or treatment of COVID-19.

Case report: Acute Talaromyces marneffei mediastinitis in an HIV-negative patient.

Talaromyces marneffei (T. marneffei) is one of the most important opportunistic human pathogens endemic in Southeast Asia. Talaromycosis, which was once regarded as an opportunistic infectious disease in patients with acquired immunodeficiency syndrome, is being increasingly reported in HIV-negative populations. Since T. marneffei infection can be localized or disseminated, patients may present with a variety of symptoms. However, mediastinal infection attributed to T. marneffei is extremely rare. We report the case of a 32-year-old female who manifested a large mediastinal mass and was eventually diagnosed as acute T. marneffei mediastinitis. The patient was HIV-negative and had no direct contact with intermediate hosts. We successfully managed to treat the patient with inhaled amphotericin B deoxycholate and observed lesion absorption in subsequent CT examinations. To our knowledge, this is the first published case of T. marneffei mediastinitis and first use of inhaled antifungal monotherapy on patients with T. marneffei infection.

Astrocyte dysfunction drives abnormal resting-state functional connectivity in depression.

Major depressive disorder (MDD) is a devastating mental disorder that affects up to 17% of the population worldwide. Although brain-wide network-level abnormalities in MDD patients via resting-state functional magnetic resonance imaging (rsfMRI) exist, the mechanisms underlying these network changes are unknown, despite their immense potential for depression diagnosis and management. Here, we show that the astrocytic calcium-deficient mice, inositol 1,4,5-trisphosphate-type-2 receptor knockout mice (Itpr2-/- mice), display abnormal rsfMRI functional connectivity (rsFC) in depression-related networks, especially decreased rsFC in medial prefrontal cortex (mPFC)-related pathways. We further uncover rsFC decreases in MDD patients highly consistent with those of Itpr2-/- mice, especially in mPFC-related pathways. Optogenetic activation of mPFC astrocytes partially enhances rsFC in depression-related networks in both Itpr2-/- and wild-type mice. Optogenetic activation of the mPFC neurons or mPFC-striatum pathway rescues disrupted rsFC and depressive-like behaviors in Itpr2-/- mice. Our results identify the previously unknown role of astrocyte dysfunction in driving rsFC abnormalities in depression.

Effects of the Short-Foot Exercise on Foot Alignment and Muscle Hypertrophy in Flatfoot Individuals: A Meta-Analysis.

This study aimed to conduct a meta-analysis of randomized controlled trials to examine the effects of the short-foot exercise (SFE) compared to foot orthosis or other types of interventions. Eligibility criteria involved participants with flatfoot engaging in the SFE compared to other forms of intervention or control groups without specific intervention. Relevant studies published before the end of June 2022 were identified from databases. A meta-analysis was performed by calculating the mean differences (MD) and standard MD (SMD) using the random effects model. Six trials with 201 patients (out of 609 records) that met selection criteria were reviewed. Five of the six trials implemented distinct interventions in the control group such as shoe insoles and muscle strengthening exercises, while in the remaining trial, controls received no intervention. The SFE group significantly reduced the navicular drop test (NDT) values (MD: -0.23; 95% confidence interval: -0.45 to -0.02; p = 0.04) and the foot posture index (FPI-6) score (MD: -0.67; 95% confidence interval: -0.98 to -0.36; p < 0.0001) when compared to the control group. The muscle hypertrophy did not differ significantly between the groups. The SFE may contribute more benefits than other intervention as it affects flatfoot individuals' foot alignment. Hence, the SFE is recommended as a beneficial dynamic support when facing flatfoot problems.

Identifying Soybean Pod Borer (Leguminivora glycinivorella) Resistance QTLs and the Mechanism of Induced Defense Using Linkage Mapping and RNA-Seq Analysis.

The soybean pod borer (Leguminivora glycinivorella) (SPB) is a major cause of soybean (Glycine max L.) yield losses in northeast Asia, thus it is desirable to elucidate the resistance mechanisms involved in soybean response to the SPB. However, few studies have mapped SPB-resistant quantitative trait loci (QTLs) and deciphered the response mechanism in soybean. Here, we selected two soybean varieties, JY93 (SPB-resistant) and K6 (SPB-sensitive), to construct F2 and F2:3 populations for QTL mapping and collected pod shells before and after SPB larvae chewed on the two parents to perform RNA-Seq, which can identify stable QTLs and explore the response mechanism of soybean to the SPB. The results show that four QTLs underlying SPB damage to seeds were detected on chromosomes 4, 9, 13, and 15. Among them, qESP-9-1 was scanned in all environments, hence it can be considered a stable QTL. All QTLs explained 0.79 to 6.09% of the phenotypic variation. Meanwhile, 2298 and 3509 DEGs were identified for JY93 and K6, respectively, after the SPB attack, and most of these genes were upregulated. Gene Ontology enrichment results indicated that the SPB-induced and differently expressed genes in both parents are involved in biological processes such as wound response, signal transduction, immune response, and phytohormone pathways. Interestingly, secondary metabolic processes such as flavonoid synthesis were only significantly enriched in the upregulated genes of JY93 after SPB chewing compared with K6. Finally, we identified 18 candidate genes related to soybean pod borer resistance through the integration of QTL mapping and RNA-Seq analysis. Seven of these genes had similar expression patterns to the mapping parents in four additional soybean germplasm after feeding by the SPB. These results provide additional knowledge of the early response and induced defense mechanisms against the SPB in soybean, which could help in breeding SPB-resistant soybean accessions.