BACKGROUND: While emotional distress, encompassing anxiety and depression, has been associated with negative clinical outcomes, its impact across various clinical departments and general hospitals has been less explored. Previous studies with limited sample sizes have examined the effectiveness of specific treatments (e.g., antidepressants) rather than a systemic management strategy for outcome improvement in non-psychiatric inpatients. To enhance the understanding of the importance of addressing mental health care needs among non-psychiatric patients in general hospitals, this study retrospectively investigated the impacts of emotional distress and the effects of early detection and management of depression and anxiety on hospital length of stay (LOS) and rate of long LOS (LLOS, i.e., LOS >30 days) in a large sample of non-psychiatric inpatients. METHODS: This retrospective cohort study included 487,871 inpatients from 20 non-psychiatric departments of a general hospital. They were divided, according to whether they underwent a novel strategy to manage emotional distress which deployed the Huaxi Emotional Distress Index (HEI) for brief screening with grading psychological services (BS-GPS), into BS-GPS ( n = 178,883) and non-BS-GPS ( n = 308,988) cohorts. The LOS and rate of LLOS between the BS-GPS and non-BS-GPS cohorts and between subcohorts with and without clinically significant anxiety and/or depression (CSAD, i.e., HEI score ≥11 on admission to the hospital) in the BS-GPS cohort were compared using univariable analyses, multilevel analyses, and/or propensity score-matched analyses, respectively. RESULTS: The detection rate of CSAD in the BS-GPS cohort varied from 2.64% (95% confidence interval [CI]: 2.49%-2.81%) to 20.50% (95% CI: 19.43%-21.62%) across the 20 departments, with a average rate of 5.36%. Significant differences were observed in both the LOS and LLOS rates between the subcohorts with CSAD (12.7 days, 535/9590) and without CSAD (9.5 days, 3800/169,293) and between the BS-GPS (9.6 days, 4335/178,883) and non-BS-GPS (10.8 days, 11,483/308,988) cohorts. These differences remained significant after controlling for confounders using propensity score-matched comparisons. A multilevel analysis indicated that BS-GPS was negatively associated with both LOS and LLOS after controlling for sociodemographics and the departments of patient discharge and remained negatively associated with LLOS after controlling additionally for the year of patient discharge. CONCLUSION Emotional distress significantly prolonged the LOS and increased the LLOS of non-psychiatric inpatients across most departments and general hospitals. These impacts were moderated by the implementation of BS-GPS. Thus, BS-GPS has the potential as an effective, resource-saving strategy for enhancing mental health care and optimizing medical resources in general hospitals.
Humans ; Retrospective Studies ; Male ; Length of Stay/statistics & numerical data* ; Female ; Middle Aged ; Adult ; Psychological Distress ; Inpatients/psychology* ; Aged ; Anxiety/diagnosis* ; Depression/diagnosis*

Nuclear receptor corepressor (NCoR1) interacts with various nuclear receptors and regulates the anabolism and catabolism of lipids. An imbalance in lipid/energy homeostasis is also an important factor in obesity and metabolic syndrome development. In this study, we found that the deletion of NCoR1 in intestinal epithelial cells (IECs) mainly activated the nuclear receptor PPARα and attenuated metabolic syndrome by stimulating thermogenesis. The increase in brown adipose tissue thermogenesis was mediated by gut-derived tricarboxylic acid cycle intermediate succinate, whose production was significantly enhanced by PPARα activation in the fed state. Additionally, NCoR1 deletion derepressed intestinal LXR, increased cholesterol excretion, and impaired duodenal lipid absorption by decreasing bile acid hydrophobicity, thereby reversing the possible negative effects of intestinal PPARα activation. Therefore, the simultaneous regulatory effect of intestinal NCoR1 on both lipid intake and energy expenditure strongly suggests that it is a promising target for developing metabolic syndrome treatment.

Pregnane X receptor (PXR) is a ligand-activated nuclear receptor that transcriptionally upregulates drug-metabolizing enzymes [e.g., cytochrome P450 3A4 (CYP3A4)] and transporters. Although the regulation of PXR target genes is well-characterized, less is known about the regulation of PXR protein level. By screening an RNAi library, we identified the F-box-only protein 44 (FBXO44) as a novel E3 ligase for PXR. PXR abundance increases upon knockdown of FBXO44, and, inversely, decreases upon overexpression of FBXO44. Further analysis revealed that FBXO44 interacts with PXR, leading to its ubiquitination and proteasomal degradation, and we determined that the F-box associated domain of FBXO44 and the ligand binding domain of PXR are required for the functional interaction. In summary, FBXO44 regulates PXR protein abundance, which has downstream consequences for CYP3A4 levels and drug-drug interactions. The results of this study provide new insight into the molecular mechanisms that regulate PXR protein level and activity and suggest the importance of considering how modulating E3 ubiquitin ligase activities will affect PXR-mediated drug metabolism.

Although somatic cells can be reprogrammed to pluripotent stem cells (PSCs) with pure chemicals, authentic pluripotency of chemically induced pluripotent stem cells (CiPSCs) has never been achieved through tetraploid complementation assay. Spontaneous reprogramming of spermatogonial stem cells (SSCs) was another non-transgenic way to obtain PSCs, but this process lacks mechanistic explanation. Here, we reconstructed the trajectory of mouse SSC reprogramming and developed a five-chemical combination, boosting the reprogramming efficiency by nearly 80- to 100-folds. More importantly, chemical induced germline-derived PSCs (5C-gPSCs), but not gPSCs and chemical induced pluripotent stem cells, had authentic pluripotency, as determined by tetraploid complementation. Mechanistically, SSCs traversed through an inverted pathway of in vivo germ cell development, exhibiting the expression signatures and DNA methylation dynamics from spermatogonia to primordial germ cells and further to epiblasts. Besides, SSC-specific imprinting control regions switched from biallelic methylated states to monoallelic methylated states by imprinting demethylation and then re-methylation on one of the two alleles in 5C-gPSCs, which was apparently distinct with the imprinting reprogramming in vivo as DNA methylation simultaneously occurred on both alleles. Our work sheds light on the unique regulatory network underpinning SSC reprogramming, providing insights to understand generic mechanisms for cell-fate decision and epigenetic-related disorders in regenerative medicine.
Male ; Mice ; Animals ; Cellular Reprogramming/genetics* ; Tetraploidy ; Pluripotent Stem Cells/metabolism* ; Induced Pluripotent Stem Cells/metabolism* ; DNA Methylation ; Spermatogonia/metabolism* ; Germ Cells/metabolism*

INTRODUCTION: Our aim was to study the prevalence of frailty and its associated factors in a subacute geriatric ward. METHODS: This was a cross-sectional study of 167 participants between June 2018 and June 2019. Baseline demographics and participants' Mini Nutritional Assessment, Geriatric Depression Scale, Mini Mental State Examination, Charlson's Comorbidity Index and LACE index scores were obtained. Functional measurements such as modified Barthel's Index scores and hand grip strength (HGS) were taken. Frailty was assessed using the Clinical Frailty Scale (CFS) and the FRAIL scale. Data on history of healthcare utilisation, medications, length of stay, selected blood investigations and presence of geriatric syndromes were also collected. RESULTS: The prevalence of pre-frailty (CFS 4) and frailty (CFS ≥ 5) was 16.2% and 63.4%, respectively. There were significant associations between CFS and age (pre-frail vs. non-frail: odds ratio [OR] 1.14, 95% confidence interval [CI] 1.04-1.25, P = 0.006; frail vs. non-frail: OR 1.08, 95% CI 1.01-1.15, P = 0.021), HGS at discharge (frail vs. non-frail: OR 0.90, 95% CI 0.82-0.99, P = 0.025), serum albumin (frail vs. non-frail: OR 0.90, 95% CI 0.82-0.99, P = 0.035) and the presence of urinary incontinence (frail vs. non-frail: OR 3.03, 95% CI 1.19-7.77, P = 0.021). CONCLUSION Frailty is highly prevalent in the subacute geriatric setting and has many associated factors. In this study, independent factors associated with frailty were age, HGS at discharge, serum albumin and urinary incontinence. This has implications for future resource allocation for frail older inpatients and may help direct further research to study the effectiveness of frailty-targeted interventions.
Humans ; Aged ; Frailty/epidemiology* ; Frail Elderly ; Hand Strength ; Prevalence ; Singapore/epidemiology* ; Cross-Sectional Studies ; Fatigue Syndrome, Chronic ; Geriatric Assessment ; Urinary Incontinence ; Serum Albumin

Animals ; Epithelial Cells ; Epithelial-Mesenchymal Transition/genetics* ; MicroRNAs/genetics* ; Rats ; Rats, Inbred SHR ; Transforming Growth Factor beta/genetics* ; Transforming Growth Factor beta1/pharmacology*

Humans ; COVID-19/epidemiology* ; Pandemics ; Orthopedics ; Orthopedic Procedures ; Telemedicine

Synechocystis sp.PCC 6803(hereafter:Synechocystis)is a model organism for studying photosynthesis,energy metabolism,and environmental stress.Although known as the first fully sequenced phototrophic organism,Synechocystis still has almost half of its proteome without func-tional annotations.In this study,by using co-fractionation coupled with liquid chromatography-tandem mass spectrometry(LC-MS/MS),we define 291 multi-protein complexes,encompassing 24,092 protein-protein interactions(PPIs)among 2062 distinct gene products.This information not only reveals the roles of photosynthesis in metabolism,cell motility,DNA repair,cell division,and other physiological processes,but also shows how protein functions vary from bacteria to higher plants due to changes in interaction partners.It also allows us to uncover the functions of hypothetical proteins,such as S110445,S110446,and S110447 involved in photosynthesis and cell motility,and Sill 334 involved in regulation of fatty acid biogenesis.Here we present the most exten-sive PPI data for Synechocystis so far,which provide critical insights into fundamental molecular mechanisms in cyanobacteria.