Protective effect of chicken yolk antibody Y against Campylobacter jejuni induced diarrhea in cats.

Campylobacter jejuni (C. jejuni) is a common pathogen that often causes diarrhea, loss of appetite, and even enteritis in domestic cats, affecting their growth and development, especially in kittens under 6 months of age. Oral passive immunization with chicken yolk antibody Y has been proved effective for the treatment of gastrointestinal pathogen infections due to its high specificity. In this study, C. jejuni was isolated from diarrheal cat feces, and the specific egg yolk antibody Y against C. jejuni was demonstrated to effectively inhibit its proliferation in vitro experiments. To evaluate the effect of anti-C. jejuni IgY, the mouse C. jejuni infection model was established and it was found that IgY could alleviate C. jejuni-induced clinical symptoms. Consistent with these results, the reduction of pro-inflammatory factors and intestinal colonization by C. jejuni in the IgY-treated groups, especially in the high dose group. We then evaluated the protective effect of IgY on young Ragdoll cats infected with C. jejuni. This specific antibody reduced the rate of feline diarrhea, protected the growth of young cats, inhibited systemic inflammatory hyperactivation, and increased fecal short-chain fatty acid concentrations. Notably, IgY may have a protective role by changing intestinal amino acid metabolism and affecting C. jejuni chemotaxis. Collectively, specific IgY is a promising therapeutic strategy for C. jejuni-induced cat diarrhea.

Dissolved organic matter influences the indigenous bacterial community and polycyclic aromatic hydrocarbons biodegradation in soils.

In polycyclic aromatic hydrocarbon (PAH) contaminated soils, bioremediation is superior to other strategies owing to its low cost and environmental friendliness. However, dissolved organic matter (DOM) and indigenous bacterial communities can affect the efficiency of PAH-degrading bacteria (PDB). This study found that exogenous PDB (C1) including the genera Acinetobacter, Stenotrophomonas, and Comamonas, decreased the bacterial diversity of Alfisol, Ultisol, Inceptisol, and Mollisol, and DOM enhanced the diffusion of PDB and the bioavailability of PAH. In addition, bacteria preferred to ingest low molecular weight DOM fractions, and the abundances of lipid-like and protein-like substances decreased by 0.12-3.03 % and 1.73-4.60 %. The DOM fractions had a more marked influence on the indigenous bacteria than the exogenous PDB, and PDB dominated the PAH biodegradation process in the soils. More COO functional groups promoted the utilization of higher molecular weight-related homologue fractions by bacteria, and lower molecular weight fractions carrying more CH2 functional groups declined during biodegradation. This study investigated the variations in bacterial communities during biodegradation and revealed the effects of DOM fractions on biodegradation in PAH-contaminated soils at the molecular level. These results will promote the development of bioremediation strategies for organics-contaminated soil and provide guidance for prediction models of soil biodegradation kinetics.

Prediction of Human Pharmacokinetics of E0703, a Novel Radioprotective Agent, Using Physiologically Based Pharmacokinetic Modeling and an Interspecies Extrapolation Approach.

E0703, a new steroidal compound optimized from estradiol, significantly increased cell proliferation and the survival rate of KM mice and beagles after ionizing radiation. In this study, we characterize its preclinical pharmacokinetics (PK) and predict its human PK using a physiologically based pharmacokinetic (PBPK) model. The preclinical PK of E0703 was studied in mice and Rhesus monkeys. Asian human clearance (CL) values for E0703 were predicted from various allometric methods. The human PK profiles of E0703 (30 mg) were predicted by the PBPK model in Gastro Plus software 9.8 (SimulationsPlus, Lancaster, CA, USA). Furthermore, tissue distribution and the human PK profiles of different administration dosages and forms were predicted. The 0.002 L/h of CL and 0.005 L of Vss in mice were calculated and optimized from observed PK data. The plasma exposure of E0703 was availably predicted by the CL using the simple allometry (SA) method. The plasma concentration-time profiles of other dosages (20 and 40 mg) and two oral administrations (30 mg) were well-fitted to the observed values. In addition, the PK profile of target organs for E0703 exhibited a higher peak concentration (Cmax) and AUC than plasma. The developed E0703-PBPK model, which is precisely applicable to multiple species, benefits from further clinical development to predict PK in humans.

The direct binding of bioactive peptide Andersonin-W1 to TLR4 expedites the healing of diabetic skin wounds.

BACKGROUND: Chronic nonhealing wounds remain a considerable challenge in clinical treatment due to excessive inflammation and impeded reepithelialization and angiogenesis. Therefore, the discovery of novel prohealing agents for chronic skin wounds are urgent and important. Amphibian-derived prohealing peptides, especially immunomodulatory peptides, provide a promising strategy for the treatment of chronic skin trauma. However, the mechanism of immunomodulatory peptides accelerating the skin wound healing remains poorly understood. METHODS: The prohealing ability of peptide Andersonin-W1 (AW1) was assessed by cell scratch, cell proliferation, transwell, and tube formation. Next, full-thickness, deep second-degree burns and diabetic full-thickness skin wounds in mice were performed to detect the therapeutic effects of AW1. Moreover, the tissue regeneration and expression of inflammatory cytokines were evaluated by hematoxylin and eosin (H&E), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry staining. Molecular docking, colocalization, and western blotting were used to explore the mechanism of AW1 in promoting wound healing. RESULTS: We provide solid evidence to display excellent prohealing effects of AW1, identified as a short antimicrobial peptide in our previous report. At relative low concentration of nM, AW1 promoted the proliferation, migration, and scratch repair of keratinocyte, macrophage proliferation, and tube formation of HUVEC. AW1 also facilitated reepithelialization, granulation regeneration, and angiogenesis, thus significantly boosting the healing of full-thickness, deep second-degree burns and diabetic skin wounds in mice. Mechanistically, in macrophages, AW1 directly bound to Toll-like receptor 4 (TLR4) in the extracellular region and regulated the downstream nuclear factor-κB (NF-κB) signaling pathway to facilitate the inflammatory factor secretion and suppress excessive inflammation induced by lipopolysaccharide (LPS). Moreover, AW1 regulated macrophage polarization to promote the transition from the inflammatory to the proliferative phase and then facilitated reepithelialization, granulation regeneration, and angiogenesis, thus exhibiting excellent therapeutic effects on diabetic skin wounds. CONCLUSIONS: AW1 modulates inflammation and the wound healing process by the TLR4/NF-κB molecular axis, thus facilitating reepithelialization, granulation regeneration, and angiogenesis. These findings not only provided a promising multifunctional prohealing drug candidate for chronic nonhealing skin wounds but also highlighted the unique roles of "small" peptides in the elucidation of "big" human disease mechanisms.

Additive renal protective effects between arctigenin and puerarin in diabetic kidney disease.

Recent studies have shown that the combined use of renin angiotensin system inhibitor, SGLT2 inhibitors and/or mineralocorticoid receptor antagonist provides additional renal protection for patients with diabetic kidney disease (DKD). Similarly, in traditional Chinese medicine, the synergistic application of multiple herbs often brings more significant therapeutic effects. However, the synergistic or additive mechanisms of traditional Chinese medicine in combination therapy are not fully understood. In our previous studies, we show that arctigenin (ATG), a major component of Fructus Arctii, attenuates proteinuria and renal injury in diabetic mice by activating PP2A, and puerarin (a class of known isoflavones) can also reduce proteinuria and renal injury in diabetic mice via activation of Sirt1. Here, we further explored the potential additive renal protection of these two compounds in diabetic mice. Research has found that ATG and puerarin have a synergistic effect in reducing albuminuria in db/db mice. Mechanistically, we found that ATG reduced NF-κB p65 phosphorylation likely through activation of PP2A while puerarin reduced p65 acetylation via Sirt1 activation. Therefore, ATG and puerarin have additive inhibitory effects on the NF-κB activation, which is a key inflammatory pathway in DKD. RNA-sequencing analysis revealed distinct pathways activated by ATG and puerarin in the diabetic kidney, which may provide an additional mechanism for their additive effects in DKD. Our study suggests that ATG and puerarin could be a new combination therapy for DKD and reveals its underlined mechanisms.

Breath volatile organic compounds for chronic kidney disease progression monitoring.

Breath analysis may provide a convenient and non-invasive method for clinical monitoring of chronic kidney disease (CKD) progression. However, few breath volatile organic compounds (VOCs) indicating progression of CKD have been reported. In this study, we used gas chromatography-mass spectrometry (GC-MS) for untargeted detection of breath VOCs in stage 1, 3, and 5 CKD patients. The results showed that, the levels of breath 4-heptanone, n-octane, and n-dodecane gradually increased from CKD stage 1 to stage 5, and their increasing rates from CKD stage 3 to stage 5 were higher than those from CKD stage 1 to stage 3. Gender, smoking habits, age, and body mass index (BMI) had insignificant impact on the levels of the three breath VOCs. The accuracies of the polynomial support vector machine (SVM) and K-nearest neighbour (KNN) models based on 4-heptanone + n-octane + n-dodecane combination in distinguishing CKD stages 1, 3, and 5 were 76.3% and 72.8%, respectively. The combination of 4-heptanone + n-octane + n-dodecane was superior to any single component for monitoring CKD progression. These discoveries have valuable implications for long-term clinical monitoring of CKD and improving our understanding of CKD.

High-Speed and Accurate Diagnosis of Gastrointestinal Disease: Learning on Endoscopy Images Using Lightweight Transformer with Local Feature Attention.

In response to the pressing need for robust disease diagnosis from gastrointestinal tract (GIT) endoscopic images, we proposed FLATer, a fast, lightweight, and highly accurate transformer-based model. FLATer consists of a residual block, a vision transformer module, and a spatial attention block, which concurrently focuses on local features and global attention. It can leverage the capabilities of both convolutional neural networks (CNNs) and vision transformers (ViT). We decomposed the classification of endoscopic images into two subtasks: a binary classification to discern between normal and pathological images and a further multi-class classification to categorize images into specific diseases, namely ulcerative colitis, polyps, and esophagitis. FLATer has exhibited exceptional prowess in these tasks, achieving 96.4% accuracy in binary classification and 99.7% accuracy in ternary classification, surpassing most existing models. Notably, FLATer could maintain impressive performance when trained from scratch, underscoring its robustness. In addition to the high precision, FLATer boasted remarkable efficiency, reaching a notable throughput of 16.4k images per second, which positions FLATer as a compelling candidate for rapid disease identification in clinical practice.

Metabolic Risk Profile and Graft Function Deterioration 2 Years After Kidney Transplant.

Importance: Studies exploring the association of body weight and metabolic status with graft function deterioration (GFD) after kidney transplantation have produced inconsistent findings. Few studies have examined whether metabolically healthy overweight or obesity (MHO) may contribute to GFD. Objective: To evaluate associations of overweight or obesity and metabolic disorders with GFD in recipients of kidney transplant. Design, Setting, and Participants: This multicenter retrospective cohort study was conducted from January 1, 2020, through June 30, 2021, with a follow-up period of 2 years after kidney transplantation. Participants included adult recipients of cadaveric kidney transplant in 4 transplantation centers in China. Participants were classified as 4 metabolic phenotypes according to their BMI and metabolic status. Data were analyzed from July to August 2023. Exposures: Overweight and obesity were characterized by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 24 or greater. Metabolic disorder was identified by existence of a minimum of 2 of 4 conditions: hypertension, hyperglycemia, increased triglyceride, and decreased high-density lipoprotein cholesterol. Main Outcome and Measures: The main outcome was GFD, defined as a decrease in estimated glomerular filtration rate of at least 25% within 6 months to 2 years after transplant. Results: A total of 1260 adult recipients of cadaveric kidney transplant (mean [SD] age, 43.97 [11.51] years; 755 [59.92%] male) were included in the study, and 127 (10.08%) participants experienced the primary outcome of GFD during follow-up. After accounting for confounding factors in multivariable analyses, overweight or obesity (odds ratio [OR], 1.64; 95% CI, 1.10-2.44; P = .02) and metabolic disorder (OR, 1.71; 95% CI, 1.12-2.63; P = .01) were associated with increased risk of GFD. The MHO subgroup exhibited a greater risk for GFD (OR, 2.37; 95% CI, 1.01-5.57; P = .048) compared with participants who did not have overweight or obesity or metabolic disorder. All components of metabolic disorder, with the exception of elevated triglyceride, were associated with GFD. There was a dose-response association of number of metabolic disorder components (OR per 1 additional condition, 1.40; 95% CI, 1.20-1.63; P < .001) and BMI (OR per 1-unit increase, 1.90; 95% CI, 1.03-1.15; P = .002) with increased risk for GFD. A nonlinear association was observed between BMI and risk of GFD. Conclusions and Relevance: In this cohort study of recipients of cadaveric kidney transplant, individuals with overweight or obesity or metabolic disorder had a significantly higher risk of experiencing GFD. Individuals with MHO had an elevated risk for graft function deterioration. Additional studies with larger sample size and longer follow-up are necessary to validate our findings.

GALNT5 functions as a suppressor of ferroptosis and a predictor of poor prognosis in pancreatic adenocarcinoma.

Mucin-type O-glycosylation, a posttranslational modification of membrane and secretory proteins, facilitates metastasis and immune escape in tumor cells. N-acetylgalactosaminyl-transferase 5 (GALNT5), the enzyme initiating mucin-type O-glycosylation, is known to advance the progression of various tumors. Yet, the comprehensive role of GALNT5 in pan-cancer scenarios remains to be elucidated. In this research, we conducted a database-centric pan-cancer expression analysis of GALNT5. We examined its aberrant expression, assessed its prognostic implications, and explored the correlations between GALNT5 expression and factors such as ferroptosis, immune cell infiltration levels, and immune checkpoint gene expression across multiple tumor types. To substantiate GALNT5's role, we analyzed cell proliferation, migration, invasion, and ferroptosis in PAAD cells after GALNT5 knockdown. Additionally, RNA-seq was employed to discern potential downstream pathways influenced by GALNT5. Our findings indicate that GALNT5 expression is heightened in the majority of tumors, correlating with the prognosis of multiple cancers. There's a notable association between GALNT5 levels and ferroptosis-related genes, immune cell infiltration, and immune checkpoint genes. In PAAD specifically, the role of GALNT5 was further probed. Knockdown of GALNT5 curtailed the proliferation, migration, and invasion capacities of PAAD cells, concurrently promoting ferroptosis. Moreover, in vivo studies demonstrated that GALNT5 inhibition stunted PAAD tumor growth. The RNA-seq analysis unveiled inflammation and immune-centric pathways, such as the TNF signaling pathway, as potential downstream conduits of GALNT5. In conclusion, our pan-cancer study underscores GALNT5 as a potential therapeutic target for enhancing PAAD prognosis, given its strong ties with ferroptosis and immune cell infiltration. Our experiments further define GALNT5 as a novel suppressor of ferroptosis.

GaitSG: Gait Recognition with SMPLs in Graph Structure.

Gait recognition aims to identify a person based on his unique walking pattern. Compared with silhouettes and skeletons, skinned multi-person linear (SMPL) models can simultaneously provide human pose and shape information and are robust to viewpoint and clothing variances. However, previous approaches have only considered SMPL parameters as a whole and are yet to explore their potential for gait recognition thoroughly. To address this problem, we concentrate on SMPL representations and propose a novel SMPL-based method named GaitSG for gait recognition, which takes SMPL parameters in the graph structure as input. Specifically, we represent the SMPL model as graph nodes and employ graph convolution techniques to effectively model the human model topology and generate discriminative gait features. Further, we utilize prior knowledge of the human body and elaborately design a novel part graph pooling block, PGPB, to encode viewpoint information explicitly. The PGPB also alleviates the physical distance-unaware limitation of the graph structure. Comprehensive experiments on public gait recognition datasets, Gait3D and CASIA-B, demonstrate that GaitSG can achieve better performance and faster convergence than existing model-based approaches. Specifically, compared with the baseline SMPLGait (3D only), our model achieves approximately twice the Rank-1 accuracy and requires three times fewer training iterations on Gait3D.

Effects of species-relevant auditory stimuli on stress in cats exposed to novel environment.

Environmental changes like vet visit could cause stress in cats. Studies have attempted to develop stress management strategies targeting sensory systems. Even though species-appropriate music which includes cat affiliative sound (e.g., cats' purring and suckling sound) has been shown to relieve stress in cats. Little is known whether the cat sound alone works in stress management. This study was conducted to investigate the effects of species-relevant auditory stimuli on stress in cats exposed to a novel environment. During the 28-day experiment periods, 20 cats received four types of sound treatments which included silence (T1), purr of cats (T2), eating sound in cats (T3), and the mixed sound of T2 and T3 (T4) in a novel environment in random orders with intervals of 1 week between treatments. Cats' behaviors were recorded during each 10-min test. Results showed that T4 reduced visual scanning (P = 0.017) without significantly affecting other behaviors, compared with other treatments. Together, the two types of cat-specific sounds did not exert pronounced effects of relieving stress on cats exposed to a novel environment.

Relationship between Macrophages and Tissue Microenvironments in Diabetic Kidneys.

Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease. Increasing evidence has suggested that inflammation is a key microenvironment involved in the development and progression of DN. Studies have confirmed that macrophage accumulation is closely related to the progression to human DN. Macrophage phenotype is highly regulated by the surrounding microenvironment in the diabetic kidneys. M1 and M2 macrophages represent distinct and sometimes coexisting functional phenotypes of the same population, with their roles implicated in pathological changes, such as in inflammation and fibrosis associated with the stage of DN. Recent findings from single-cell RNA sequencing of macrophages in DN further confirmed the heterogeneity and plasticity of the macrophages. In addition, intrinsic renal cells interact with macrophages directly or through changes in the tissue microenvironment. Macrophage depletion, modification of its polarization, and autophagy could be potential new therapies for DN.

Superhydrophobic, stretchable kirigami pencil-on-paper multifunctional device platform.

Wearable electronics with applications in healthcare, human-machine interfaces, and robotics often explore complex manufacturing procedures and are not disposable. Although the use of conductive pencil patterns on cellulose paper provides inexpensive, disposable sensors, they have limited stretchability and are easily affected by variations in the ambient environment. This work presents the combination of pencil-on-paper with the hydrophobic fumed SiO2 (Hf-SiO2) coating and stretchable kirigami structures from laser cutting to prepare a superhydrophobic, stretchable pencil-on-paper multifunctional sensing platform. The resulting sensor exhibits a large response to NO2 gas at elevated temperature from self-heating, which is minimally affected by the variations in the ambient temperature and relative humidity, as well as mechanical deformations such as bending and stretching states. The integrated temperature sensor and electrodes with the sensing platform can accurately detect temperature and electrophysiological signals to alert for adverse thermal effects and cardiopulmonary diseases. The thermal therapy and electrical stimulation provided by the platform can also deliver effective means to battle against inflammation/infection and treat chronic wounds. The superhydrophobic pencil-onpaper multifunctional device platform provides a low-cost, disposable solution to disease diagnostic confirmation and early treatment for personal and population health.

Shear wave elastography parameters adds prognostic value to adverse outcome in kidney transplantation recipients.

INTRODUCTION: The tissue stiffness of donor kidneys in transplantation may increase due to pathological changes such as glomerulosclerosis and interstitial fibrosis, and those changes associate worse outcomes in kidney transplantation recipients. Ultrasound elastography is a noninvasive imaging examination with the ability to quantitatively reflect tissue stiffness. Aim of this study was to evaluate the prognostic value of ultrasound elastography for adverse kidney outcome in kidney transplantation recipients. METHODS: Shear wave elastography (SWE) examinations were performed by two independent operators in kidney transplantation recipients. The primary outcome was a composite of kidney graft deterioration, all-cause re-hospitalization, and all-cause mortality. Survival analysis was calculated by Kaplan-Meier curves with the log-rank test and Cox regression analysis. RESULTS: A total of 161 patients (mean age 46 years, 63.4% men) were followed for a median of 20.1 months. 27 patients (16.77%) reached the primary endpoint. The mean and median tissue stiffness at the medulla (hazard ratio: 1.265 and 1.229, respectively), estimated glomerular filtration rate (eGFR), and serum albumin level were associated with the primary outcome in univariate Cox regression. Adding mean or median medulla SWE to a baseline model containing eGFR and albumin significantly improved its discrimination (C-statistics: 0.736 for the baseline, 0.766 and 0.772 for the model added mean and median medulla SWE, respectively). CONCLUSION: The medullary tissue stiffness of kidney allograft measured by shear wave elastography may provide incremental prognostic value to adverse outcomes in kidney transplantation recipients. Including SWE parameters in kidney transplantation recipients management could be considered to improve risk stratification.

Facile fabrication of PMIA composite separator with bi-functional sodium-alginate coating layer for synergistically increasing performance of lithium-ion batteries.

Lack of safety and unenough electrochemical performance have been known as a fundamental obstacle limiting the extensive application of lithium-ion batteries (LIBs). It is really preferable but challenging to fabricate thermal-response separator with shutdown function for high-performance LIBs. Herein, a thermal-response sodium-alginate modified PMIA (Na-Alg/PMIA) composite separator with shutdown function was designed and prepared by non-solvent phase induced separation (NIPs). PMIA and Na-Alg are combined by hydrogen bonding. While Na-Alg increases polar groups and makes Li+ easy to be transported, a small amount of Na+ can provide Li+ active sites, accelerate Li+ deposition coating and effectively inhibit the formation of Li dendrites. The as-prepared Na-Alg/PMIA composite separators can close pores at 200 °C and maintain dimensional integrity without obvious thermal shrinkage. In addition, the Na-Alg/PMIA composite separators has excellent wettability and ionic conductivity, resulting in high specific capacity and retention during the charge-discharge cycles. After 50 cycles, the capacity retention of cells with the Na-Alg/PMIA-20 composite separator is 84.3 %. At 2 C, cells with the Na-Alg/PMIA-20 composite separators still held 101.1 mAh g-1. This facile yet effective method improves the electrochemical performance while ensuring the safety of the LIBs, which provides ideas for the commercial application of PMIA separators.

Paxlovid for hospitalized COVID-19 patients with chronic kidney disease.

BACKGROUND: COVID-19 causes significant mortality during the recent pandemic. Data regarding the effectiveness of Paxlovid on COVID-19 patients with chronic kidney disease (CKD, eGFR <90 ml/min) are limited. METHODS: A retrospective cohort study was performed on the clinical data of the hospitalized adult patients with confirmed COVID-19 infection collected at Renji Hospital from April 7, 2022 to June 21, 2022. The association of Paxlovid treatment with early (within 5 days post diagnosis) or late (5 days or later post diagnosis) initiation time with clinical outcomes was assessed by Cox proportional hazards regression model with time-dependent covariates. RESULT: 1279 of 2387 enrollees were included in the study. Patients with early initiation of Paxlovid had a lower all-cause death rate compared to those with late initiation or without Paxlovid treatment (P = 0.046). For the CKD patients with Charlson comorbidity index (CCI) > 7, the early initiation of Paxlovid was associated with a lower all-cause death rate compared to the later initiation or the lack of Paxlovid treatment (P = 0.041). Cox regression analyses revealed that eGFR (HR 4.21 [95%, CI 1.62-10.99]), Paxlovid treatment (0.32 [0.13-0.77]), CCI (4.32 [1.64-11.40]), ICU admission (2.65 [1.09-6.49]), hsCRP (3.88 [1.46-7.80]), chronic liver disease (4.02 [1.09-14.85]) were the independent risk factors for all-cause death for CKD patients after adjusting for demographics and biochemical indexes. CONCLUSIONS: All-cause death, invasive ventilation, and ICU admission were all significantly lowered by an early initiation of Paxlovid treatment in COVID-19 patients with severe CKD.

Inflammation and coagulation abnormalities via the activation of the HMGB1­RAGE/NF­κB and F2/Rho pathways in lung injury induced by acute hypoxia.

High­altitude acute hypoxia is commonly associated with respiratory cardiovascular diseases. The inability to adapt to acute hypoxia may lead to cardiovascular dysfunction, lung injury and even death. Therefore, understanding the molecular basis of the adaptation to high­altitude acute hypoxia may reveal novel therapeutic approaches with which to counteract the detrimental consequences of hypoxia. In the present study, a high­altitude environment was simulated in a rat model in order to investigate the role of the high mobility group protein­1 (HMGB1)/receptor for advanced glycation end products (RAGE)/NF­κB and F2/Rho signaling pathways in lung injury induced by acute hypoxia. It was found that acute hypoxia caused inflammation through the HMGB1/RAGE/NF­κB pathway and coagulation dysfunction through the F2/Rho pathway, both of which may be key processes in acute hypoxia­induced lung injury. The present study provides new insight into the molecular basis of lung injury induced by acute hypoxia. The simultaneous activation of the HMGB1/RAGE/NF­κB and F2/Rho signaling pathways plays a critical role in hypoxia­induced inflammatory responses and coagulation abnormalities, and provides a theoretical basis for the development of potential therapeutic strategies.

Nirmatrelvir/ritonavir for patients with SARS-CoV-2 infection and impaired kidney function during the Omicron surge.

Background: Nirmatrelvir/ritonavir has demonstrated effectiveness in high-risk patients with coronavirus disease 2019 (COVID-19). However, investigations on the efficacy and safety of nirmatrelvir/ritonavir in patients with kidney dysfunction are limited. Methods: Data were collected from the patients admitted to a COVID-19 referral center in Shanghai, China. Patients were at least 18 years of age and had a baseline estimated glomerular filtration rate (eGFR) of <60 ml/min/1·73 m2. The primary endpoint was a composite of all-cause mortality, intensive care unit admission, or cardiovascular events. The secondary endpoint was viral shedding. Results: Among the 195 participants, 73 received nirmatrelvir/ritonavir. A lower risk of the primary endpoint was observed in nirmatrelvir/ritonavir recipients compared with non-recipients [adjusted HR 0.56 (95% CI: 0.32-0.96); p = 0.035]. Nirmatrelvir/ritonavir recipients experienced a shorter duration of viral shedding [adjusted HR 3·70 (95%CI: 2.60-5.28); p < 0.001) and faster viral load clearance versus non-recipients. Among the nirmatrelvir/ritonavir users, earlier initiation of nirmatrelvir/ritonavir within 5 days since COVID-19 diagnosis was related with shorter viral shedding time (adjusted HR 7.84 [95% CI: 3.28-18.76]; p < 0.001) compared to late initiation. No patients reported serious adverse events during treatment. Conclusion: Our findings support the early initiation of nirmatrelvir/ritonavir for high-risk patients with impaired kidney function. This could improve patient outcomes and shorten the viral shedding period.

Adaptive immune dysfunction in patients with COVID-19 and impaired kidney function during the omicron surge.

BACKGROUND: Little is known about the characteristics of lymphocyte subsets and the association with patient outcomes in COVID-19 with and without impaired kidney function. METHODS: Lymphocyte subsets were compared in COVID-19 patients with or without kidney dysfunction. The primary outcome was a composite of all-cause mortality or intensive care unit admission. Secondary outcomes included duration of viral shedding, length of hospital stay, and acute kidney injury. RESULTS: Lymphocyte subset cell counts demonstrated the lowest in patients with severe/critical COVID-19 and kidney dysfunction. Among all lymphocyte subset parameters, Th cell count was the most significant indicator for outcomes. ROC of the combined model of Th cell count and eGFR presented better predictive value than that of the other parameters. Th cell count <394.5 cells/µl and eGFR <87.5 ml/min/1·73m2 were independently associated with poor outcomes. The propensity score matching analysis revealed consistent results. CONCLUSIONS: Reduced Th cell count and eGFR may be applied as promising predictive indicators for identifying COVID-19 patients with high risk and poor outcomes.