Genetic and Epigenetic Associations with Post-Transplant Diabetes Mellitus.

Post-transplant diabetes mellitus (PTDM) is a common complication of solid organ transplantation. PTDM prevalence varies due to different diabetes definitions. Consensus guidelines for the diagnosis of PTDM have been published based on random blood glucose levels, glycated hemoglobin (HbA1c), and oral glucose tolerance test (OGTT). The task of diagnosing PTDM continues to pose challenges, given the potential for diabetes to manifest at different time points after transplantation, thus demanding constant clinical vigilance and repeated testing. Interpreting HbA1c levels can be challenging after renal transplantation. Pre-transplant risk factors for PTDM include obesity, sedentary lifestyle, family history of diabetes, ethnicity (e.g., African-Caribbean or South Asian ancestry), and genetic risk factors. Risk factors for PTDM include immunosuppressive drugs, weight gain, hepatitis C, and cytomegalovirus infection. There is also emerging evidence that genetic and epigenetic variation in the organ transplant recipient may influence the risk of developing PTDM. This review outlines many known risk factors for PTDM and details some of the pathways, genetic variants, and epigenetic features associated with PTDM. Improved understanding of established and emerging risk factors may help identify people at risk of developing PTDM and may reduce the risk of developing PTDM or improve the management of this complication of organ transplantation.

Stratification of glioma based on stemness scores in bulk and single-cell transcriptomes.

BACKGROUND: Brain tumours are known to have a high mortality and morbidity rate due to their localised and frequent invasive growth. The concept that glioma resistance could originate from the dissimilarity in the vulnerability of clonogenic glial stem cells to chemotherapeutic drugs and radiation has driven the scientific community to reexamine the comprehension of glioma growth and strategies that target these cells or modify their stemness. METHODS: Based on the enrichment scores of 12 stemness signatures, we identified glioma subtypes in both tumour bulks and single cells by clustering analysis. Furthermore, we comprehensively compared molecular and clinical features among the glioma subtypes. RESULTS: Consistently, in seven different datasets, hierarchical clustering uncovered three subtypes of glioma, termed Stem-H, Stem-M, and Stem-L, with high, medium, and low stemness signatures, respectively. Stem-H and Stem-L exhibited the most unfavorable and favourable overall and disease-free survival, respectively. Stem-H showed the highest enrichment scores of the EMT, invasion, proliferation, differentiation, and metastasis processes signatures, while Stem-L displayed the lowest. Stem-H harboured a greater proportion of late-stage tumours compared to Stem-L. Moreover, Stem-H manifested higher tumour mutation burden, DNA damage repair and cell cycle activity, intratumour heterogeneity, and a more frequent incidence of TP53 and EGFR mutations than Stem-L. In contrast, Stem-L had higher O6-Methylguanine-DNA Methyltransferase (MGMT) methylation levels. CONCLUSION: The classification of glioma based on stemness may offer new insights into the biology of the tumour, as well as more accurate clinical management of the disease.

Thermal and solutal heat transport investigations of second order fluid with the application of Cattaneo-Christov theory.

The present examination of mass and heat communication looks at the impact of induced magnetic field, variable thermal conductivity, and activation energy on the flow of second-order liquid across a stretched surface. The mass-heat transfer is also treated using the Model for generalized Fourier and Fick's Laws. The model equations are transformed as needed to produce a system of nonlinear ODEs, which are then numerically solved with the help of BVP4C integrated MATLAB approach. The heat-mass flow parameters are analyzed by the table and graphs. An increment in the estimations of 2nd grade fluid parameter (ß) with magnetic field parameter (M) increase the speed sketch. For the stronger estimations of Schmidt number (Sc), parameter of magnetic field (M) and Eckert number (Ec) have the growing behavior on the temperature profile.

Age, sex, and APOE gene-specific associations between dynapenic obesity and dementia in a large cohort.

OBJECTIVE: To investigate the associations between dynapenic obesity and the risk of dementia, and the modifying effects of age, sex, and the APOE gene, using a large population-based cohort. METHODS: 279,884 participants aged 55 and above from the UK Biobank were included. The participants were classified into four categories based on body mass index and hand grip strength: healthy, obesity, dynapenia, and dynapenic obesity. The incident dementia was identified based on linked hospital records and death register data. Cox proportional hazards regression models were used to estimate the associations, followed by age-, sex-, and apolipoprotein E (APOE) gene-stratified analyses. RESULTS: During the median follow-up of 12.4 years, 5,170 (1.8%) participants developed dementia. Compared with the healthy group, participants with dynapenic obesity had 67% higher dementia risk (hazard ratio [HR]: 1.67, 95% confidence interval [CI]: 1.44-1.94). Compared with the healthy group, higher risks of dementia in participants with dynapenic obesity were respectively observed in male (HR: 2.03, 95% CI: 1.65-2.50), younger (<65 years, HR: 1.97, 95% CI: 1.55-2.50), and non-ε4-carrier (HR: 1.97, 95% CI: 1.60-2.44) (all P for interaction <0.05). In participants under 65 years and non-ε4-carrier, those with dynapenic obesity had the highest risk of dementia (HR: 2.63, 95% CI: 1.91-3.62), compared with the healthy group (P for second order interaction = 0.026). CONCLUSIONS: Dynapenic obesity is associated with increased risks of dementia, especially in participants under 65 years and non-ε4-carrier, suggesting the importance of managing dynapenic obesity in the prevention of cognition-related disorders.

Numerical investigation of the impact of temperature-dependent thermal conductivity and viscosity on thermo-particle heat transfer through stationary sphere and using plume.

Nanofluids have a wide range of applications due to their unique properties, such as enhanced thermal conductivity, convective heat transfer, and mass transfer. These applications can be seen in heat exchangers, cooling systems, and electronic devices to improve thermal performance. To enhance the cooling efficiency and lifespan of electronic devices such as smartphones, televisions, and computers nanofluids are used. These novel types of fluids can be used in energy storage systems, cancer treatment, imaging, and drug deliveryKeeping in mind, the real-time applications in engineering, industry, and science, the current study is carried out. In the present study for heat and mass transportation, the two-phase Buongiorno model for nanofluid is employed to scrutinize Brownian motion and thermophoresis aspects using stationary sphere and plume region. The temperature-dependent viscosity and thermal conductivity effects are encountered in momentum and energy equations, respectively are encountered. The proposed mechanism in the partial differential equations having dimensional form is converted to a non-dimensional form using appropriate dimensionless variables. The solution of the current non-linear and coupled model is obtained using the finite difference method. The numerical solutions presented in graphs and tables indicate that along with heat and mass transfer phenomena are entirely dependent on thermophoresis, Brownian motion, temperature-dependent viscosity, and thermal conductivity. The results indicate that the quantitative behavior of the velocity field is enhanced by increasing values of thermal conductivity variation parameters for both the sphere and the plume region at each position. On the other hand, the reverse trend is noted against the rising magnitudes of the viscosity variation parameter, thermophoresis parameter, and Brownian diffusion parameter. Additionally, the temperature in the plume region declines to enhance thermal conductivity variation parameter. A test for grid independence was performed by considering various grid points. Excellent solution accuracy has been seen as the number of grid points has risen. This ensures the validity and accuracy of the currently employed method. The current results are compared with already published solutions for the validation of the current model for specific cases. It has been noted that there is excellent agreement between both of the results. This close agreement between the results indicates the validation of the current solutions.

Trajectories of Body Mass Index and Waist Circumference in Relation to the Risk of Cardiac Arrhythmia: A Prospective Cohort Study.

BACKGROUND: The aim of the current study was to explore the trajectories, variabilities, and cumulative exposures of body mass index (BMI) and waist circumference (WC) with cardiac arrhythmia (CA) risks. METHODS: In total, 35,739 adults from the Kailuan study were included. BMI and WC were measured repeatedly during the 2006-2010 waves. CA was identified via electrocardiogram diagnosis. BMI and WC trajectories were fitted using a group-based trajectory model. The associations were estimated using Cox proportional hazards models. RESULTS: We identified four stable trajectories for BMI and WC, respectively. Neither the BMI trajectories nor the baseline BMI values were associated with the risk of CA. Compared to the low-stable WC group, participants in the high-stable WC group had a higher risk of CA (hazard ratio (HR) = 1.40, 95% confidence interval (CI): 1.06, 1.86). Interestingly, the cumulative exposures of BMI and WC instead of their variabilities were associated with the risk of CA. In the stratified analyses, the positive associations of the high-stable WC group with the risk of CA were found in females only (HR = 1.98, 95% CI: 1.02, 3.83). CONCLUSIONS: A high-stable WC trajectory is associated with a higher risk of CA among Chinese female adults, underscoring the potential of WC rather than BMI to identify adults who are at risk.

Transition to healthier lifestyle associated with reduced risk of incident dementia and decreased hippocampal atrophy.

BACKGROUND: Research has estimated the associations of lifestyle at one-time point with the risk of dementia and hippocampal volume, but the impact of lifestyle transition on dementia and hippocampal volume remains unclear. This study aims to examine the associations of lifestyle transition with the risk of dementia and hippocampal volume. METHODS: Based on data from the UK Biobank, a weighted lifestyle score was constructed by incorporating six lifestyle factors. Within each baseline lifestyle group (i.e., healthy, intermediate, and unhealthy), lifestyle transition was classified into decline, maintenance, and improvement. Cox proportional hazard regression was used to estimate the association of lifestyle transition and incident dementia (N = 16,305). A multiple linear regression model was used to estimate the association between lifestyle transition and hippocampal volume (N = 5849). RESULTS: During a median follow-up period of 8.6 years, 120 (0.7 %) dementia events were documented. Among participants with healthy baseline lifestyles, the improvement group had a lower risk of incident dementia (HR: 0.18, 95 % CI: 0.04-0.81) and a larger hippocampal volume (ß = 111.69, P = 0.026) than the decline group. Similar results were observed among participants with intermediate baseline lifestyles regarding dementia risk but not hippocampal volume. No benefits were observed in the improvement group among those with unhealthy baseline lifestyles. LIMITATIONS: A lower incidence of dementia than other cohort study and this may have resulted in an underestimation of the risk of dementia. CONCLUSIONS: Earlier transitions to healthier lifestyle were associated with reduced risk of incident dementia and decreased hippocampal atrophy.

A Novel Metabolomic Aging Clock Predicting Health Outcomes and Its Genetic and Modifiable Factors.

Existing metabolomic clocks exhibit deficiencies in capturing the heterogeneous aging rates among individuals with the same chronological age. Yet, the modifiable and non-modifiable factors in metabolomic aging have not been systematically studied. Here, a new aging measure-MetaboAgeMort-is developed using metabolomic profiles from 239,291 UK Biobank participants for 10-year all-cause mortality prediction. The MetaboAgeMort showed significant associations with all-cause mortality, cause-specific mortality, and diverse incident diseases. Adding MetaboAgeMort to a conventional risk factors model improved the predictive ability of 10-year mortality. A total of 99 modifiable factors across seven categories are identified for MetaboAgeMort. Among these, 16 factors representing pulmonary function, body composition, socioeconomic status, dietary quality, smoking status, alcohol intake, and disease status showed quantitatively stronger associations. The genetic analyses revealed 99 genomic risk loci and 271 genes associated with MetaboAgeMort. The tissue-enrichment analysis showed significant enrichment in liver. While the external validation of the MetaboAgeMort is required, this study illuminates heterogeneous metabolomic aging across the same age, providing avenues for identifying high-risk individuals, developing anti-aging therapies, and personalizing interventions, thus promoting healthy aging and longevity.

Identification of novel pathways and immune profiles related to sarcopenia.

Introduction: Sarcopenia is a progressive deterioration of skeletal muscle mass strength and function. Methods: To uncover the underlying cellular and biological mechanisms, we studied the association between sarcopenia's three stages and the patient's ethnicity, identified a gene regulatory network based on motif enrichment in the upregulated gene set of sarcopenia, and compared the immunological landscape among sarcopenia stages. Results: We found that sarcopenia (S) was associated with GnRH, neurotrophin, Rap1, Ras, and p53 signaling pathways. Low muscle mass (LMM) patients showed activated pathways of VEGF signaling, B-cell receptor signaling, ErbB signaling, and T-cell receptor signaling. Low muscle mass and physical performance (LMM_LP) patients showed lower enrichment scores in B-cell receptor signaling, apoptosis, HIF-1 signaling, and the adaptive immune response pathways. Five common genes among DEGs and the elastic net regression model, TTC39DP, SLURP1, LCE1C, PTCD2P1, and OR7E109P, were expressed between S patients and healthy controls. SLURP1 and LCE1C showed the highest expression levels among sarcopenic Chinese descent than Caucasians and Afro-Caribbeans. Gene regulatory analysis of top upregulated genes in S patients yielded a top-scoring regulon containing GATA1, GATA2, and GATA3 as master regulators and nine predicted direct target genes. Two genes were associated with locomotion: POSTN and SLURP1. TTC39DP upregulation was associated with a better prognosis and stronger immune profile in S patients. The upregulation of SLURP1 and LCE1C was associated with a worse prognosis and weaker immune profile. Conclusion: This study provides new insight into sarcopenia's cellular and immunological prospects and evaluates the age and sarcopenia-related modifications of skeletal muscle.

Gene set enrichment analysis identifies immune subtypes of kidney renal clear cell carcinoma with significantly different molecular and clinical properties.

Background: Kidney renal clear cell carcinoma (KIRC) is the most prevalent renal malignancy, marked by a high abundance of tumor-infiltrating lymphocytes (TILs) and an unfavorable prognosis upon metastasis. Numerous studies have demonstrated that KIRC possesses a tumor microenvironment that is highly heterogeneous, and this is associated with significant variations in the effectiveness of most first-line drugs administered to KIRC patients. Therefore, it is crucial to classify KIRC based on the tumor microenvironment, although these subtyping techniques are still inadequate. Methods: By applying gene set enrichment scores of 28 immune signatures, we conducted a hierarchical clustering of KIRC and determined its immune subtypes. In addition, we conducted a comprehensive exploration of the molecular and clinical features of these subtypes, including survival prognosis, proliferation, stemness, angiogenesis, tumor microenvironment, genome instability, intratumor heterogeneity, and pathway enrichment. Results: Through cluster analysis, two immune subtypes of KIRC were identified and termed Immunity-High (Immunity-H) and Immunity-Low (Immunity-L). This clustering outcome was consistent in four independent KIRC cohorts. The subtype Immunity-H exhibited elevated levels of TILs, tumor aneuploidy, homologous recombination deficiency, stemness, and proliferation potential, along with a poorer prognosis for survival. Despite this, the Immunity-L subtype demonstrated elevated intratumor heterogeneity and a stronger angiogenesis signature in contrast to Immunity-H. According to the results of pathway enrichment analysis, the Immunity-H subtype was found to be highly enriched in immunological, oncogenic, and metabolic pathways, whereas the Immunity-L subtype was highly enriched in angiogenic, neuroactive ligand-receptor interaction, and PPAR pathways. Conclusions: Based on the enrichment of immune signatures in the tumor microenvironment, KIRC can be categorized into two immune subtypes. The two subtypes demonstrate considerably distinct molecular and clinical features. In KIRC, an increase in immune infiltration is linked to a poor prognosis. Patients with Immunity-H KIRC may exhibit active responses to PPAR and immune checkpoint inhibitors, whereas patients with Immunity-L may manifest favorable responses to anti-angiogenic agents and immune checkpoint inhibitors. The immunological classification provides molecular insights into KIRC immunity, as well as clinical implications for the management of this disease.

Controlled delivery of a neurotransmitter-agonist conjugate for functional recovery after severe spinal cord injury.

Despite considerable unmet medical needs, effective pharmacological treatments that promote functional recovery after spinal cord injury remain limited. Although multiple pathological events are implicated in spinal cord injuries, the development of a microinvasive pharmacological approach that simultaneously targets the different mechanisms involved in spinal cord injury remains a formidable challenge. Here we report the development of a microinvasive nanodrug delivery system that consists of amphiphilic copolymers responsive to reactive oxygen species and an encapsulated neurotransmitter-conjugated KCC2 agonist. Upon intravenous administration, the nanodrugs enter the injured spinal cord due to a disruption in the blood-spinal cord barrier and disassembly due to damage-triggered reactive oxygen species. The nanodrugs exhibit dual functions in the injured spinal cord: scavenging accumulated reactive oxygen species in the lesion, thereby protecting spared tissues, and facilitating the integration of spared circuits into the host spinal cord through targeted modulation of inhibitory neurons. This microinvasive treatment leads to notable functional recovery in rats with contusive spinal cord injury.

Association of Sarcopenia with Cognitive Function and Dementia Risk Score: A National Prospective Cohort Study.

The relationship between skeletal muscle and cognitive disorders has drawn increasing attention. This study aims to examine the associations of sarcopenia with cognitive function and dementia risk score. Data on 1978 participants (aged 65 years and older) from the 2011 wave of the China Health and Retirement Longitudinal Study, with four follow-up waves to 2018, were used. Cognitive function was assessed by four dimensions, with a lower score indicating lower cognitive function. Dementia risk was assessed by a risk score using the Rotterdam Study Basic Dementia Risk Model (BDRM), with a higher score indicating a greater risk. Sarcopenia was defined when low muscle mass plus low muscle strength or low physical performance were met. We used generalized estimating equations to examine the associations of sarcopenia. In the fully adjusted models, sarcopenia was significantly associated with lower cognitive function (standardized, ß = -0.15; 95% CIs: -0.26, -0.04) and a higher BDRM score (standardized, ß = 0.42; 95% CIs: 0.29, 0.55). Our findings may provide a new avenue for alleviating the burden of cognitive disorders by preventing sarcopenia.

Visit-to-visit HbA1c variability, dementia, and hippocampal atrophy among adults without diabetes.

OBJECTIVES: Adults without diabetes are not completely healthy; they are probably heterogeneous with several potential health problems. The management of hemoglobin A1c (HbA1c) is crucial among patients with diabetes; but whether similar management strategy is needed for adults without diabetes is unclear. Thus, this study aimed to investigate the associations of visit-to-visit HbA1c variability with incident dementia and hippocampal volume among middle-aged and older adults without diabetes, providing potential insights into this question. METHODS: We conducted a prospective analysis for incident dementia in 10,792 participants (mean age 58.9 years, 47.8 % men) from the UK Biobank. A subgroup of 3793 participants (mean age 57.8 years, 48.6 % men) was included in the analysis for hippocampal volume. We defined HbA1c variability as the difference in HbA1c divided by the mean HbA1c over the 2 sequential visits ([latter - former]/mean). Dementia was identified using hospital inpatient records with ICD-9 codes. T1-structural brain magnetic resonance imaging was conducted to derive hippocampal volume (normalized for head size). The nonlinear and linear associations were examined using restricted cubic spline (RCS) models, Cox regression models, and multiple linear regression models. RESULTS: During a mean follow-up (since the second round) of 8.4 years, 90 (0.8 %) participants developed dementia. The RCS models suggested no significant nonlinear associations of HbA1c variability with incident dementia and hippocampal volume, respectively (All P > 0.05). Above an optimal cutoff of HbA1c variability at 0.08, high HbA1c variability (increment in HbA1c) was associated with an increased risk of dementia (Hazard Ratio, 1.88; 95 % Confidence Interval, 1.13 to 3.14, P = 0.015), and lower hippocampal volume (coefficient, -96.84 mm3, P = 0.037), respectively, in models with adjustment of covariates including age, sex, etc. Similar results were found for a different cut-off of 0. A series of sensitivity analyses verified the robustness of the findings. CONCLUSIONS: Among middle-aged and older adults without diabetes, increasing visit-to-visit HbA1c variability was associated with an increased dementia risk and lower hippocampal volume. The findings highlight the importance of monitoring and controlling HbA1c fluctuation in apparently healthy adults without diabetes.

Downregulation of UBE4B promotes CNS axon regrowth and functional recovery after stroke.

The limited intrinsic regrowth capacity of corticospinal axons impedes functional recovery after cortical stroke. Although the mammalian target of rapamycin (mTOR) and p53 pathways have been identified as the key intrinsic pathways regulating CNS axon regrowth, little is known about the key upstream regulatory mechanism by which these two major pathways control CNS axon regrowth. By screening genes that regulate ubiquitin-mediated degradation of the p53 proteins in mice, we found that ubiquitination factor E4B (UBE4B) represses axonal regrowth in retinal ganglion cells and corticospinal neurons. We found that axonal regrowth induced by UBE4B depletion depended on the cooperative activation of p53 and mTOR. Importantly, overexpression of UbV.E4B, a competitive inhibitor of UBE4B, in corticospinal neurons promoted corticospinal axon sprouting and facilitated the recovery of corticospinal axon-dependent function in a cortical stroke model. Thus, our findings provide a translatable strategy for restoring corticospinal tract-dependent functions after cortical stroke.

Porous microneedle patch with sustained delivery of extracellular vesicles mitigates severe spinal cord injury.

The transplantation of mesenchymal stem cells-derived secretome, particularly extracellular vesicles is a promising therapy to suppress spinal cord injury-triggered neuroinflammation. However, efficient delivery of extracellular vesicles to the injured spinal cord, with minimal damage, remains a challenge. Here we present a device for the delivery of extracellular vesicles to treat spinal cord injury. We show that the device incorporating mesenchymal stem cells and porous microneedles enables the delivery of extracellular vesicles. We demonstrate that topical application to the spinal cord lesion beneath the spinal dura, does not damage the lesion. We evaluate the efficacy of our device in a contusive spinal cord injury model and find that it reduces the cavity and scar tissue formation, promotes angiogenesis, and improves survival of nearby tissues and axons. Importantly, the sustained delivery of extracellular vesicles for at least 7 days results in significant functional recovery. Thus, our device provides an efficient and sustained extracellular vesicles delivery platform for spinal cord injury treatment.

High expression of the ANXA3 gene promotes immune infiltration and improves tumor prognosis in ovarian serous carcinoma using bioinformatics analyses.

Background: Annexin A3 (ANXA3) expression change is related to tumor cell proliferation and might serve as a novel diagnostic and prognostic biomarker for cancer. However, its roles and mechanisms in ovarian serous cystadenocarcinoma (OV) have not yet been elucidated. This study aimed to investigate ANXA3 expression in OV, its association with immune infiltrates, and its prognostic roles in OV. Methods: The clinical data and gene expression profiles of 379 patients (189 with low ANXA3 expression and 190 with high ANXA3 level) with an OV diagnosis confirmed by histopathological examination were downloaded from The Cancer Genome Atlas database (https://portal.gdc.cancer.gov). The survival rate and expected survival time were used to measure disease prognosis. Survival curves were generated using the Kaplan-Meier method. Cox regression and a nomogram prediction model were used to analyze the relationship between ANXA3 and the survival rate. Logistic regression was used to analyze the relationship between clinicopathological features and ANXA3 expression. Protein-protein interactions among ANXA3 relevant proteins were established using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. The signaling pathways interacting with ANXA3 were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Results: High ANXA3 expression significantly correlated with lymph node infiltration (odds ratio =0.448, P=0.025) and overall favorable survival (hazard ratio =0.69, P=0.011). The Federation International of Gynecology and Obstetrics stages, primary therapy outcome, age, and residual tumor might serve as independent prognostic factors, whereas the ANXA3 levels could not independently predict OV prognosis. ANXA3 expression negatively and statistically (P<0.05) correlated with lymphatic invasion in Th17 cells, T follicular helper (TFH) cells, and T effector memory cells. The GO/KEGG pathway enrichment analysis confirmed the involvement of three signaling pathways in controlling the interaction of extracellular vesicles with ANXA3. Conclusions: High ANXA3 expression may contribute to tumor inhibition and a favorable prognosis to a certain extent by promoting the infiltration of TFH cells and Th17 lymphocytes or acting on extracellular vesicles inducing a stronger T-cell-mediated immunity against tumor cells.

Evaluation of the role of vaccination in the COVID-19 pandemic based on the data from the 50 U.S. States.

Vaccination is considered as the ultimate weapon to end the pandemic. However, the role of vaccines in the pandemic remains controversial. To explore the impact of vaccination on the COVID-19 pandemic, we used logistic regression models to predict numbers of population-adjusted confirmed cases, deaths, intensive care unit (ICU) cases, case fatality rates and ICU admission rates of COVID-19 in the 50 U.S. states, based on 17 related variables. The logistic regression analysis showed that percentages of people vaccinated correlated inversely with the numbers of COVID-19 deaths and case fatality rates but showed no significant correlation with numbers of confirmed cases or ICU cases, or ICU admission rates. The Spearman correlation analysis showed that the percentages of people vaccinated correlated inversely with the numbers of COVID-19 deaths, ICU cases, ICU case rates, and case fatality rates but showed no significant correlation with numbers of confirmed cases. The number of deaths and mortality in the group after the vaccine usage were significantly lower than those in the group before the vaccine usage. However, after delta became the dominant strain, there were no longer significant differences in the number of deaths and the mortality rate between before and after delta became the dominant strain, although vaccines were used in both periods. Vaccination can significantly reduce COVID-19 deaths and mortality, while it cannot reduce the risk of COVID-19 infection. In addition to vaccination, other measures, such as social distancing, remain important in containing COVID-19 transmission and lower the risk of COVID-19 severe outcomes.

Gallbladder volvulus.

Gallbladder volvulus is a rare entity. The condition results in rotation of the gallbladder on its mesentery along the axis of cystic duct and artery. Gallbladder volvulus is a condition in which the organ twists on its long axis to the point where its vascular supply is compromised.

Comparisons of the immunological landscape of COVID-19 patients based on sex and disease severity by multi-omics analysis.

OBJECTIVE: To determine the differences in the immune response against SARS-CoV-2 infection of patients based on sex and disease severity. METHODS: We used an analytical framework of 382 transcriptional modules and multi-omics analyses to discriminate COVID-19 patients based on sex and disease severity. RESULTS: Male and female patients overexpressed modules related to the innate immune response. The expression of modules related to the adaptive immune response showed lower enrichment levels in males than females. Inflammation modules showed ascending overexpression in male and female patients, while a higher level was observed in severe female patients. Moderate female patients demonstrated significant overexpression to interferon, cytolytic lymphocyte, T & B cells, and erythrocytes modules. Moderate female patients showed a higher adaptive immune response than males matched group. Pathways involved in metabolism dysregulation and Hippo signaling were upregulated in females than in male patients. Females and moderate cases showed higher levels of metabolic dysregulation. CONCLUSIONS: The immune landscape in COVID-19 patients was noticeably different between the sexes, and these differences may highlight disease vulnerability in males. This study suggested that certain treatments that increase or decrease the immune responses to SARS-CoV-2 might be necessary for male and female patients at certain disease stages.

A biocompatible two-photon absorbing fluorescent mitochondrial probe for deep in vivo bioimaging.

Mitochondria, key organelles which keep in tune with energy demands for eukaryotic cells, are firmly associated with neurological conditions and post-traumatic rehabilitation. In vivo fluorescence imaging of mitochondria, especially with deep tissue penetration, would open a window to investigate the actual context of the brain. However, the depth of traditional two-photon mitochondrial fluorescence imaging is still limited due to the poor biological compatibility or low two-photon absorption cross-sections. A biocompatible mitochondria-targeted two-photon fluorescent dye (FO2) with an excellent two-photon absorption cross-section (the maximum of 1184 GM at 790 nm) and low cellular toxicity was designed and synthesized to overcome this problem. With this dye, we reached an imaging depth of ca. 640 µm during mitochondrial imaging of cortical cells in live animals. FO2 could be an excellent mitochondrial probe for live animal neural imaging to investigate the function and dysfunction of mitochondria in the brain.