Design, synthesis, and biological evaluation of imidazolidinone derivatives as potent PPARα/δ agonists for the treatment of cholestatic liver diseases.

Cholestatic liver disease (CLD) represents a significant and growing public health concern, and there is a lack of effective therapeutic drug in clinical practice. Peroxisome proliferator-activator receptors α/δ (PPARα/δ) are regarded as potential therapeutic targets for CLD. In this study, a series of novel imidazolidinone PPARα/δ agonists were developed, and the preferred compound 8 displayed potent and well-balanced agonistic activity.

LTX-315 is a novel broad-spectrum antimicrobial peptide against clinical multidrug-resistant bacteria.

Introduction: Infections stemming from multidrug-resistant bacteria present a substantial threat to public health today. Discovering or synthesizing novel compounds is crucial to alleviate this pressing situation.

Objective: The main purpose of this study is to verify the antibacterial activity of LTX-315 and explore its primary action mode.

Counterintuitive DNA destabilization by monovalent salt at high concentrations due to overcharging.

Monovalent salts are generally believed to stabilize DNA duplex by weakening inter-strand electrostatic repulsion. Unexpectedly, our force-induced hairpin unzipping experiments and thermal melting experiments show that LiCl, NaCl, KCl, RbCl, and CsCl at concentrations beyond ~1 M destabilize DNA, RNA, and RNA-DNA duplexes. The two types of experiments yield different changes in free energy during melting, while the results that high concentration monovalent salts destabilize duplexes are common.

Effects of the interaction between body mass index and dietary patterns on severe NAFLD incidence: A prospective cohort study.

Background: It remains unclear whether the associations between dietary patterns and non-alcoholic fatty liver disease (NAFLD) vary by body mass index (BMI). We aimed to explore the association between dietary patterns and severe NAFLD incidence, and further investigate the interaction of BMI with dietary patterns.

Methods: In a prospective cohort study using UK Biobank data, we included White participants with baseline food frequency questionnaire (FFQ) information.

Scaling Laws for Protein Folding under Confinement.

Spatial confinement significantly affects protein folding. Without the confinement provided by chaperones, many proteins cannot fold correctly. However, the quantitative effect of confinement on protein folding remains elusive.

Correction: Association of daytime napping with incidence of chronic kidney disease and end-stage kidney disease: A prospective observational study.

[This corrects the article DOI: 10.1371/journal.pone.

A high-throughput system for drug screening based on the movement analysis of zebrafish.

Zebrafish is a highly advantageous model animal for drug screening and toxicity evaluation thanks to its amenability to optical imaging (i.e., transparency), possession of organ structures similar to humans, and the ease with which disease models can be established.

Study on the effect factors of discharge readiness of total hip arthroplasty patients.

Introduction: In order to explore the correlation between discharge readiness and Harris score or self-care ability of patients undergoing total hip arthroplasty (THA) based on the enhanced recovery after surgery (ERAS) concept. We carried out this single center retrospective study.

Methods: We enrolled 331 patients who underwent THA.

Combined Chemotherapy and Immunotherapy Induction for Screening of Patients with Cervical Esophageal Carcinoma for Subsequent Local Treatment: A New Treatment Paradigm.

Background: Definitive chemoradiotherapy is recommended as the primary treatment for cervical esophageal carcinoma (CEC). However, local control rates remain unsatisfactory for some patients. Therefore, in this study, we introduced a new treatment paradigm for individuals with CEC, customizing the choice between subsequent local treatments based on their response to induction chemotherapy and immunotherapy.

From Chips-in-Lab to Point-of-Care Live Cell Device: Development of a Microfluidic Device for On-Site Cell Culture and High-Throughput Drug Screening.

Live cell assays provide real-time data of cellular responses. In combination with microfluidics, applications such as automated and high-throughput drug screening on live cells can be accomplished in small devices. However, their application in point-of-care testing (POCT) is limited by the requirement for bulky equipment to maintain optimal cell culture conditions.

Achieving deep intratumoral penetration and multimodal combined therapy for tumor through algal photosynthesis.

Background: Elevated interstitial fluid pressure within tumors, resulting from impaired lymphatic drainage, constitutes a critical barrier to effective drug penetration and therapeutic outcomes.

Results: In this study, based on the photosynthetic characteristics of algae, an active drug carrier (CP@ICG) derived from Chlorella pyrenoidosa (CP) was designed and constructed. Leveraging the hypoxia tropism and phototropism exhibited by CP, we achieved targeted transport of the carrier to tumor sites.

Sijunzi decoction, a classical Chinese herbal formula, improves fatigue symptoms with changes in gut microbiota in chronic fatigue syndrome: A randomized, double-blind, placebo-controlled, multi-center clinical trial.

Backgroud: Chronic fatigue syndrome (CFS) severely impact patients' quality of life and lacks well-acknowledged drug therapy. Sijunzi decoction (SJZD), a classical Chinese herbal formula, has been widely used for spleen deficiency syndrome like fatigue in China. However, there is a lack of evidence on the efficacy of SJZD in treating CFS.

Design, synthesis, and biological evaluation of piperazine derivatives as pan-PPARs agonists for the treatment of liver fibrosis.

Liver fibrosis is commonly occurred in chronic liver diseases, but there is no approved drug for clinical use. The nuclear receptor peroxisome proliferator-activated receptors (PPARs) could not only regulate metabolic homeostasis but also possess anti-inflammatory and antifibrotic effects, and pan-PPARs agonist was considered as a potential anti-liver fibrosis agent. In this study, a series of novel piperazine pan-PPARs agonists were developed, and the preferred compound 12 displayed potent and well-balanced pan-PPARs agonistic activity.

Association of daytime napping with incidence of chronic kidney disease and end-stage kidney disease: A prospective observational study.

Background And Aims: Few studies have examined the relationship between daytime napping and risk of kidney diseases. We aimed to investigate the association of daytime napping with the incidence of chronic kidney disease (CKD) and end-stage kidney disease (ESKD). We also examined whether sleep duration modified the association of nap with CKD or ESKD.

Dietary habits and nutrition status in esophageal cancer patients after esophageal reconstruction.

Background: Surgery is the cornerstone of the treatment of esophageal cancer (EC). This study is to evaluate the dietary habits and nutrition status in EC patients who underwent esophagectomy followed by esophageal reconstruction.

Methods: This retrospective study included patients with EC who underwent esophagectomy followed by esophageal reconstruction in the Department of Thoracic Surgery I of Peking University Cancer Hospital between February 2014 and December 2018.

Discovery of Novel PD-L1 Small-Molecular Inhibitors with Potent Anti-tumor Immune Activity.

Programmed death-ligand 1 (PD-L1) has surfaced as a promising therapeutic target for various cancers due to its pivotal role in facilitating tumor immune evasion. Herein, we report a series of novel small-molecule PD-L1 inhibitors exhibiting remarkable inhibitory activity against the PD-1/PD-L1 interaction (: IC = 1.3 nM) and reinstating the suppressive effect of PD-L1 on T cells (: EC = 152.

Long-Term Survival and Recurrence Patterns in Locally Advanced Esophageal Squamous Cell Carcinoma Patients with Pathologic Complete Response After Neoadjuvant Chemotherapy Followed by Surgery.

Background: The higher pathologic complete response (pCR) after neoadjuvant chemoradiotherapy compared with neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC) has not translated into significant gains in overall survival. Data on the long-term survival of patients who obtained a pCR after neoadjuvant chemotherapy are scarce. Therefore, this study aimed to evaluate the long-term prognosis and recurrence patterns in these patients.

Kidney Function Measures and Mortality: A Mendelian Randomization Study.

Rationale & Objective: Individuals with a low estimated glomerular filtration rate (eGFR) are at a high risk of death. However, the causes underpinning this association are largely uncertain. This study aimed to assess the causal relationship of low eGFR with all-cause and cause-specific mortality.

Collaborative multidisciplinary management and expertise of cT2-3 locally advanced operable esophageal squamous cell carcinoma: a report of two cases.

Background: The accurate clinical staging of esophageal squamous cell carcinoma (ESCC) is pivotal for guiding treatment strategies. However, the current precision in staging for clinical T (cT)2 and cT3 stages remains unsatisfactory. This article discusses the role of multidisciplinary teams (MDTs) in the clinical staging and formulation of neoadjuvant treatment strategies for locally advanced operable ESCC.

Clinical study of NFNC in the treatment of acute exacerbation chronic obstructive pulmonary disease patients with respiratory failure.

Background: Most patients with acute exacerbation chronic obstructive pulmonary disease (AECOPD) have respiratory failure that necessitates active correction and the improvement of oxygenation is particularly important during treatment. High flow nasal cannula (HFNC) oxygen therapy is a non-invasive respiratory aid that is widely used in the clinic that improves oxygenation state, reduces dead space ventilation and breathing effort, protects the loss of cilia in the airways, and improves patient comfort.

Aim: To compare HFNC and non-invasive positive pressure ventilation in the treatment of patients with AECOPD.

Cystatin C-based estimated glomerular filtration rate and risk of stroke in the general population: a prospective cohort study.

Background: Previous results on the association between the estimated glomerular filtration rate (eGFR) and stroke are mixed. Most studies derived the eGFR from serum creatinine, which is affected by non-kidney determinants and thus has possibly biased the association with stroke risk.

Methods: In this cohort study, we included 429 566 UK Biobank participants (94.