Bidirectional Association between Sarcopenia and Depressive Symptoms among Chinese Middle- and Older-Aged Adults: Longitudinal Observational Study.

BACKGROUND: The study aimed to examine the bidirectional relationship between sarcopenia and depressive symptoms in a national, community-based cohort study, despite the unclear temporal sequence demonstrated previously. METHODS: Data were derived from four waves (2011 baseline and 2013, 2015, and 2018 follow-ups) of the China Health and Retirement Longitudinal Study (CHARLS). A total of 17,708 participants aged 45 years or older who had baseline data on both sarcopenia status and depressive symptoms in 2011 were included in the study. For the two cohort analyses, a total of 8092 adults without depressive symptoms and 11,292 participants without sarcopenia in 2011 were included. Sarcopenia status was defined according to the Asian Working Group for Sarcopenia 2019 (AWGS 2019) criteria. Depressive symptoms were defined as a score of 20 or higher on the 10-item Center for Epidemiologic Studies Depressive Scale (CES-D-10). Cox proportional hazard regression models were conducted to examine the risk of depressive symptoms and sarcopenia risk, while cross-lagged panel models were used to examine the temporal sequence between depressive symptoms and sarcopenia over time. RESULTS: During a total of 48,305.1 person-years follow-up, 1262 cases of incident depressive symptoms were identified. Sarcopenia exhibited a dose-response relationship with a higher risk of depressive symptoms (HR = 1.7, 95%CI: 1.2-2.3 for sarcopenia, and HR = 1.5, 95%CI: 1.2-1.8 for possible sarcopenia, p trend < 0.001). In the second cohort analysis, 240 incident sarcopenia cases were identified over 39,621.1 person-years. Depressive symptoms (HR = 1.5, 95%CI: 1.2-2.0) are significantly associated with a higher risk of developing sarcopenia after multivariable adjustment (p < 0.001, Cross-lagged panel analyses demonstrated that depressive symptoms were associated with subsequent sarcopenia (ß = 0.003, p < 0.001). Simultaneously, baseline sarcopenia was also associated with subsequent depressive symptoms (ß = 0.428, p < 0.001). CONCLUSION: This study identified a bidirectional relationship between depressive symptoms and sarcopenia. It seems more probable that baseline sarcopenia is associated with subsequent depressive symptoms in a stronger pattern than the reverse pathway. The interlinkage indicated that maintaining normal muscle mass and strength may serve as a crucial intervention strategy for alleviating mood disorders.

A novel model combining genes associated with disulfidptosis and glycolysis to predict breast cancer prognosis, molecular subtypes, and treatment response.

Breast cancer (BC) is a heterogeneous malignancy with a dismal prognosis. Disulfidptosis is a novel type of regulated cell death that happens in the presence of glucose deficiency and is linked to the metabolic process of glycolysis. However, the mechanism of action of disulfidptosis and glycolysis-related genes (DGRG) in BC, as well as their prognostic value in BC patients, remain unknown. After identifying the differentially expressed DGRG in normal and BC tissues, a number of machine learning algorithms were utilized to select essential prognostic genes to develop a model, including SLC7A11, CACNA1H, SDC1, CHST1, and TFF3. The expression characteristics of these genes were then examined using single-cell RNA sequencing, and BC was classified into three clusters using "ConsensusClusterPlus" based on these genes. The DGRG model's median risk score can categorize BC patients into high-risk and low-risk groups. Furthermore, we investigated variations in clinical landscape, immunoinvasion analysis, tumor immune dysfunction and rejection (TIDE), and medication sensitivity in patients in the DGRG model's high- and low-risk groups. Patients in the low-risk group performed better on immunological and chemotherapeutic therapies and had lower TIDE scores. In conclusion, the DGRG model we developed has significant clinical application potential because it can accurately predict the prognosis of BC, TME, and pharmacological treatment responses.

Brain abnormalities in survivors of COVID-19 after 2-year recovery: a functional MRI study.

Background: A variety of symptoms, particularly cognitive, psychiatric and neurological symptoms, may persist for a long time among individuals recovering from COVID-19. However, the underlying mechanism of these brain abnormalities remains unclear. This study aimed to investigate the long-term neuroimaging effects of COVID-19 infection on brain functional activities using resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Fifty-two survivors 27 months after infection (mild-moderate group: 25 participants, severe-critical: 27 participants), from our previous community participants, along with 35 healthy controls, were recruited to undergo fMRI scans and comprehensive cognitive function measurements. Participants were evaluated by subjective assessment of Cognitive Failures Questionnaire-14 (CFQ-14) and Fatigue Scale-14 (FS-14), and objective assessment of Montreal Cognitive Assessment (MoCA), N-back, and Simple Reaction Time (SRT). Each had rs-fMRI at 3T. Measures such as the amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo) were calculated. Findings: Compared with healthy controls, survivors of mild-moderate acute symptoms group and severe-critical group had a significantly higher score of cognitive complains involving cognitive failure and mental fatigue. However, there was no difference of cognitive complaints between two groups of COVID-19 survivors. The performance of three groups was similar on the score of MoCA, N-back and SRT. The rs-fMRI results showed that COVID-19 survivors exhibited significantly increased ALFF values in the left putamen (PUT.L), right inferior temporal gyrus (ITG.R) and right pallidum (PAL.R), while decreased ALFF values were observed in the right superior parietal gyrus (SPG.R) and left superior temporal gyrus (STG.L). Additionally, decreased ReHo values in the right precentral gyrus (PreCG.R), left postcentral gyrus (PoCG.L), left calcarine fissure and surrounding cortex (CAL.L) and left superior temporal gyrus (STG.L). Furthermore, significant negative correlations between the ReHo values in the STG.L, and CFQ-14 and mental fatigue were found. Interpretation: This long-term study suggests that individuals recovering from COVID-19 continue to experience cognitive complaints, psychiatric and neurological symptoms, and brain functional alteration. The rs-fMRI results indicated that the changes in brain function in regions such as the putamen, temporal lobe, and superior parietal gyrus may contribute to cognitive complaints in individuals with long COVID even after 2-year infection. Funding: The National Programs for Brain Science and Brain-like Intelligence Technology of China, the National Natural Science Foundation of China, Natural Science Foundation of Beijing Municipality of China, and the National Key Research and Development Program of China.

Galleria mellonella in vitro model for chromoblastomycosis shows large differences in virulence between isolates.

BACKGROUND: Chromoblastomycosis is the World Health Organization (WHO)-recognized fungal implantation disease that eventually leads to severe mutilation. Cladophialophora carrionii (C. carrionii) is one of the agents. However, the pathogenesis of C. carrionii is not fully investigated yet. METHODS: We investigated the pathogenic potential of the fungus in a Galleria mellonella (G. mellonella) larvae infection model. Six strains of C. carrionii, and three of its environmental relative C. yegresii were tested. The G. mellonella model was also applied to determine antifungal efficacy of amphotericin B, itraconazole, voriconazole, posaconazole, and terbinafine. RESULTS: All strains were able to infect the larvae, but virulence potentials were strain-specific and showed no correlation with clinical background of the respective isolate. Survival of larvae also varied with infection dose, and with growth speed and melanization of the fungus. Posaconazole and voriconazole exhibited best activity against Cladophialophora, followed by itraconazole and terbinafine, while limited efficacy was seen for amphotericin B. CONCLUSION: Infection behavior deviates significantly between strains. In vitro antifungal susceptibility of tested strains only partly explained the limited treatment efficacy in vivo.

Spin-degree manipulation for one-dimensional room-temperature ferromagnetism in a haldane system.

The intricate correlation between lattice geometry, topological behavior and charge degrees of freedom plays a key role in determining the physical and chemical properties of a quantum-magnetic system. Herein, we investigate the introduction of the unusual oxidation state as an alternative pathway to modulate the magnetic ground state in the well-known S = 1 Haldane system nickelate Y2BaNiO5 (YBNO). YBNO is topologically reduced to incorporate d9-Ni+ (S = 1/2) in the one-dimensional Haldane chain system. The random distribution of Ni+ for the first time results in the emergence of a one-dimensional ferromagnetic phase with a transition temperature far above room temperature. Theoretical calculations reveal that the antiferromagnetic interplay can evolve into ferromagnetic interactions with the presence of oxygen vacancies, which promotes the formation of ferromagnetic order within one-dimensional nickel chains. The unusual electronic instabilities in the nickel-based Haldane system may offer new possibilities towards unconventional physical and chemical properties from quantum interactions.

Proteome-Wide Analysis of Lysine 2-Hydroxyisobutyrylation in Aspergillus fumigatus.

Aspergillus fumigatus is the significant causative agent in cases of invasive aspergillosis, leading to a high mortality rate in immunocompromised patients. A comprehensive understanding of its growth patterns and metabolic processes within the host is a critical prerequisite for the development of effective antifungal strategies. Lysine 2-hydroxyisobutyrylation (Khib) is a highly conserved protein posttranslational modifications (PTM) found in various organisms. In this study, we investigate the biological impact of Khib in A. fumigatus. Using a combination of antibody enrichment with the conventional LC-MS/MS method, the pattern of Khib-modification in proteins and their respective sites were analyzed in a wild type strain of A. fumigatus. Our findings revealed 3494 Khib-modified proteins with a total of 18,091 modified sites in this strain. Functional enrichment analysis indicated that these Khib-modified proteins participate in a diverse range of cellular functions, spanning various subcellular locations such as ribosome biosynthesis, protein synthesis and nucleocytoplasmic transport. Notably, when compared with other reported eukaryotes, A. fumigatus exhibited consistently higher numbers of Khib-modified proteins, suggesting the potential significance of this modification in this organism. An interesting observation is the prevalence of Khib modifications in most enzymes involved in the ergosterol synthesis pathway. The insights gathered from this study provide new avenue for studying PTM-associated mechanisms in fungal growth and offer potential implication for antifungal drug development.

Integration of eQTL and machine learning to dissect causal genes with pleiotropic effects in genetic regulation networks of seed cotton yield.

The dissection of a gene regulatory network (GRN) that complements the genome-wide association study (GWAS) locus and the crosstalk underlying multiple agronomical traits remains a major challenge. In this study, we generate 558 transcriptional profiles of lint-bearing ovules at one day post-anthesis from a selective core cotton germplasm, from which 12,207 expression quantitative trait loci (eQTLs) are identified. Sixty-six known phenotypic GWAS loci are colocalized with 1,090 eQTLs, forming 38 functional GRNs associated predominantly with seed yield. Of the eGenes, 34 exhibit pleiotropic effects. Combining the eQTLs within the seed yield GRNs significantly increases the portion of narrow-sense heritability. The extreme gradient boosting (XGBoost) machine learning approach is applied to predict seed cotton yield phenotypes on the basis of gene expression. Top-ranking eGenes (NF-YB3, FLA2, and GRDP1) derived with pleiotropic effects on yield traits are validated, along with their potential roles by correlation analysis, domestication selection analysis, and transgenic plants.

Accuracy of lung and diaphragm ultrasound in predicting infant weaning outcomes: a systematic review and meta-analysis.

Background: Although lung and diaphragm ultrasound are valuable tools for predicting weaning results in adults with MV, their relevance in children is debatable. The goal of this meta-analysis was to determine the predictive value of lung and diaphragm ultrasound in newborn weaning outcomes. Methods: For eligible studies, the databases MEDLINE, Web of Science, Cochrane Library, PubMed, and Embase were thoroughly searched. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) method was used to evaluate the study's quality. Results were gathered for sensitivity, specificity, diagnostic odds ratio (DOR), and the area under the curve of summary receiver operating characteristic curves (AUSROC). To investigate the causes of heterogeneity, subgroup analyses and meta-regression were conducted. Results: A total of 11 studies were suitable for inclusion in the meta-analysis, which included 828 patients. The pooled sensitivity and specificity of lung ultrasound (LUS) were 0.88 (95%CI, 0.85-0.90) and 0.81 (95%CI, 0.75-0.87), respectively. The DOR for diaphragmatic excursion (DE) is 13.17 (95%CI, 5.65-30.71). The AUSROC for diaphragm thickening fraction (DTF) is 0.86 (95%CI, 0.82-0.89). The most sensitive and specific method is LUS. The DE and DTF were the key areas where study heterogeneity was evident. Conclusions: Lung ultrasonography is an extremely accurate method for predicting weaning results in MV infants. DTF outperforms DE in terms of diaphragm ultrasound predictive power.

Comparative genomics predict specific genes in potential mucorales identification.

Mucoralean fungi could cause mucormycosis in humans, particularly in immunodeficient individuals and those with diabetes mellitus or trauma. With plenty of species and genera, their molecular identification and pathogenicity have a large deviation. Reported cases of mucormycosis showed frequent occurrence in Rhizopus species, Mucor species, and Lichtheimia species. We analyzed the whole genome sequences of 25 species of the top 10 Mucorales genera, along with another 22 important pathogenic non-Mucorales species, to dig the target genes for monitoring Mucorales species and identify potential genomic imprints of virulence in them. Mucorales-specific genes have been found in various orthogroups extracted by Python script, while genus-specific genes were annotated covering cellular structure, biochemistry metabolism, molecular processing, and signal transduction. Proteins related to the virulence of Mucorales species varied with distinct significance in copy numbers, in which Orthofinder was conducted. Based on our fresh retrospective analysis of mucormycosis, a comparative genomic analysis of pathogenic Mucorales was conducted in more frequent pathogens. Specific orthologs between Mucorales and non-Mucoralean pathogenic fungi were discussed in detail. Referring to the previously reported virulence proteins, we included more frequent pathogenic Mucorales and compared them in Mucorales species and non-Mucorales species. Besides, more samples are needed to further verify the potential target genes.

Calibration of local chemical pressure by optical probe.

Chemical stabilization of a high-pressure metastable state is a major challenge for the development of advanced materials. Although chemical pressure (Pchem) can effectively simulate the effect of physical pressure (Pphy), experimental calibration of the pressure passed to local structural motifs, denoted as local chemical pressure (Pchem-Δ) which significantly governs the function of solid materials, remains absent due to the challenge of probing techniques. Here we establish an innovative methodology to experimentally calibrate the Pchem-Δ and build a bridge between Pchem and Pphy via an optical probe strategy. Site-selective Bi3+-traced REVO4 (RE = Y, Gd) is adopted as a prototype to introduce Bi3+ optical probes and on-site sense of the Pchem-Δ experienced by the REO8 motif. The cell compression of RE0.98Bi0.02VO4 under Pphy is chemically simulated by smaller-ion substitution (Sc3+ → RE3+) in RE0.98-xScxBi0.02VO4. The consistent red shift (Δλ) of the emission spectra of Bi3+, which is dominated by locally pressure-induced REO8 dodecahedral variation in RE0.98Bi0.02VO4 (Pphy) and RE0.98-xScxBi0.02VO4 (Pchem-Δ), respectively, is evidence of their similar pressure-dependent local structure evolution. This innovative Δλ-based experimental calibration of Pchem-Δ in the crystal-field dimension portrays the anisotropic transmission of Pchem to the local structure and builds a bridge between Pchem-Δ and Pphy to guide a new perspective for affordable and practical interception of metastable states.

The Domestic Isolation of Terbinafine- and Itraconazole-Resistant Trichophyton indotineae in Chinese Mainland.

BACKGROUND: Trichophyton indotineae, a new species of dermatophytes, has become a significant concern in treating dermatophytosis due to the high level of terbinafine resistance reported in India and even worldwide. OBJECTIVES: This study aimed to report the terbinafine- and itraconazole-resistant T. indotineae in Chinese mainland, by identifying the phylogenetic classification of the isolate strain, and detecting the drug resistance, gene mutation and expression. PATIENTS/METHODS: The skin scales of the patient were cultured on SDA and the isolate was authenticated by DNA sequencing and MALDI-TOF MS. Antifungal susceptibility testing was performed following the M38-A2 CLSI protocol to examine the MICs values of terbinafine, itraconazole, fluconazole, etc. The strain was screened for mutations in the squalene epoxidase (SQLE) gene by Sanger sequencing and detected the expression of CYP51A and CYP51B by qRT-PCR. RESULTS: A multi-resistant ITS genotype VIII sibling of the T. mentagrophytes complex (T. indotineae) was isolated in Chinese mainland. The strain harbored high terbinafine MIC of > 32 µg/mL and itraconazole MIC of 1.0 µg/mL, which was identified a mutation in the squalene epoxidase gene with amino acid substitution (Phe397Leu, mutation 1191C > A). In addition, overexpression of CYP51A and CYP51B was observed. With multiple relapses, the patient finally achieved clinical cure by itraconazole pulse therapy and topical clotrimazole cream for 5 weeks. CONCLUSIONS: The first domestic strain of terbinafine- and itraconazole-resistant T. indotineae from a patient in Chinese mainland was isolated. Itraconazole pulse therapy can be an effective method for the treatment of T. indotineae.

The phenotype and prediction of long-term physical, mental and cognitive COVID-19 sequelae 20 months after recovery, a community-based cohort study in China.

Long-term sequelae clustering phenotypes are important for precise health care management in COVID-19 survivors. We reported findings for 1000 survivors 20 months after diagnosis of COVID-19 in a community-based cohort in China. Sequelae symptoms were collected from a validated questionnaire covering 27 symptoms involved in five organ systems including self-reported physical condition, dyspnea, cognitive function and mental health. The generalized symptoms were reported with the highest rate (60.7%), followed by the mental (48.3%), cardiopulmonary (39.8%), neurological (37.1%; cognitive impairment, 15.6%), and digestive symptoms (19.1%). Four clusters were identified by latent class analysis: 44.9% no or mild group (cluster 1), 29.2% moderate group with mainly physical impairment (cluster 2), 9.6% moderate group with mainly cognitive and mental health impairment (cluster 3), and 16.3% severe group (cluster 4). Physical comorbidities or history of mental disorders, longer hospitalization periods and severe acute illness predicted severe group. For moderate group, adults less than 60 years, with physical comorbidities and severe acute illness were more likely to have physical symptoms, while adult women with longer hospitalization stays had increased risk of cognitive and mental health impairment. Overall, among more than half of community COVID-19 survivors who presented moderate or severe sequelae 20 months after recovery, three-tenth had physical vulnerability that may require physical therapy aiming to improve functioning, one-tenth mental or cognitive vulnerable cases need psychotherapy and cognitive rehabilitation, and one-sixth severe group needs multidisciplinary clinical management. The remaining half is free to clinical intervention. Our findings introduced an important framework to map numerous symptoms to precise classification of the clinical sequelae phenotype and provide information to guide future stratified recovery interventions.

A systematic review and meta-analysis of long term physical and mental sequelae of COVID-19 pandemic: call for research priority and action.

The long-term physical and mental sequelae of COVID-19 are a growing public health concern, yet there is considerable uncertainty about their prevalence, persistence and predictors. We conducted a comprehensive, up-to-date meta-analysis of survivors' health consequences and sequelae for COVID-19. PubMed, Embase and the Cochrane Library were searched through Sep 30th, 2021. Observational studies that reported the prevalence of sequelae of COVID-19 were included. Two reviewers independently undertook the data extraction and quality assessment. Of the 36,625 records identified, a total of 151 studies were included involving 1,285,407 participants from thirty-two countries. At least one sequelae symptom occurred in 50.1% (95% CI 45.4-54.8) of COVID-19 survivors for up to 12 months after infection. The most common investigation findings included abnormalities on lung CT (56.9%, 95% CI 46.2-67.3) and abnormal pulmonary function tests (45.6%, 95% CI 36.3-55.0), followed by generalized symptoms, such as fatigue (28.7%, 95% CI 21.0-37.0), psychiatric symptoms (19.7%, 95% CI 16.1-23.6) mainly depression (18.3%, 95% CI 13.3-23.8) and PTSD (17.9%, 95% CI 11.6-25.3), and neurological symptoms (18.7%, 95% CI 16.2-21.4), such as cognitive deficits (19.7%, 95% CI 8.8-33.4) and memory impairment (17.5%, 95% CI 8.1-29.6). Subgroup analysis showed that participants with a higher risk of long-term sequelae were older, mostly male, living in a high-income country, with more severe status at acute infection. Individuals with severe infection suffered more from PTSD, sleep disturbance, cognitive deficits, concentration impairment, and gustatory dysfunction. Survivors with mild infection had high burden of anxiety and memory impairment after recovery. Our findings suggest that after recovery from acute COVID-19, half of survivors still have a high burden of either physical or mental sequelae up to at least 12 months. It is important to provide urgent and appropriate prevention and intervention management to preclude persistent or emerging long-term sequelae and to promote the physical and psychiatric wellbeing of COVID-19 survivors.

In Vitro Antifungal Activity of Azoles and Other Antifungal Agents Against Pathogenic Yeasts from Vulvovaginal Candidiasis in China.

BACKGROUND: Vulvovaginal candidiasis (VVC) is a public health issue worldwide. Little is known of the optimal treatment of recurrent VVC (RVVC) has not been established. OBJECTIVE: Through the in vitro antifungal susceptibility profiling of VVC isolates, we hope to foster significant improvements in the control and treatment of this disease. METHODS: Candida isolates from VVC patients were collected from 12 hospitals in 10 cities across China. Species were identified by phenotype analysis and DNA sequencing. Species were identified by phenotype analysis and DNA sequencing. Susceptibilities to 11 drugs were determined by Clinical and Laboratory Standards Institute broth microdilution. RESULTS: 543 strains were isolated from those VVC patients enrolled in this study, of which, 15.7% were from RVVC. The most commonly identified species was C. albicans (460, 84.71%), and the most commonly non-albicans Candida spp. (NAC) was C. glabrata (47, 8.66%). NAC also included C. Krusei, Meyerozyma Guillermondii, Meyerozyma Caribbica, C. Tropicalis, C. Parapsilosis, and C. Nivariensis. Most C. albicans isolates were susceptible to caspofungin (99.8%), followed by fluconazole (92%) and voriconazole (82.6%). The proportion of C. albicans strains with wild type (WT) MICs that were susceptible to amphotericin B and caspofungin were 98%, followed by posaconazole at 95%, itraconazole at 86%, fluconazole at 74% and voriconazole at 54%. The fluconazole MICs for C. albicans were lower than those for NAC (P < 0.05), while the itraconazole MICs showing no significant difference (P > 0.05). The susceptible rate of uncomplicated VVC to fluconazole was 92%. The proportion of WT strains to fluconazole in RVVC was much lower than that in other types of VVC (67 vs. 77%, P < 0.05). However, the proportions of WT strains to itraconazole in RVVC was over 85%, which was much higher than that to fluconazole (87 vs. 67%, P < 0.05). CONCLUSIONS: C. albicans was still the predominant pathogen for VVC in China, while C. glabrata was the main species in NAC. Fluconazole could still be used as an empirical treatment for uncomplicated VVC. However, fluconazole may not be the first choice for the therapy of RVVC. In such cases, itraconazole appears to be the more appropriate treatment. As for VVC caused by NAC, nonfluconazole drugs, such as itraconazole, may be a good choice.

Biofilm Alterations on the Stepwise Acquisition of Fluconazole-resistant Candida Albicans Isolates.

By assessing and comparing the phenotypic changes on the stepwise acquisition of fluconazole resistant Candida albicans isolates, we could find and describe the relationship between drug resistance and biofilm formation ability in a series of clonal strains. Methods: We performed antifungal susceptibility of five drugs (fluconazole, itraconazole, voriconazole, caspofungin and amphotericin B) to further verify the antifungal activity of the six isolates in vitro. Then we combined hyphal formation assay, cell surface hydrophobicity test positively related to adherence ability, and biofilm assays in vitro to observe and compare the phenotypic characteristics of our six clonal strains. Results: Biofilm capability is enhanced for four drug- intermediate strains, whereas the initial susceptible strain and the final resistant strain are both poor in adherence, hyphal growth and biofilm formation. Conclusions: It was suggested that the biofilm formation ability were not absolutely related to the degree of fluconazole resistance.