Single-cell transcriptomic atlas of blood and lung from mice infected with SARS-CoV-2 revealing distinct virulence characteristics between prototype and Omicron BA.1 strain.

The markedly reduced pathogenicity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron variant in comparison to earlier strains has raised critical questions regarding its underlying mechanisms. To elucidate the host immune responses driving these differences, we performed single-cell transcriptomic profiling of lung and blood samples from human angiotensin-converting enzyme 2 (hACE2) transgenic mice infected with either the SARS-CoV-2 prototype strain or the Omicron BA.1 variant at 5 days post-inoculation.

Whole Exome Sequencing in Chinese Pediatric Patients With Nephrolithiasis.

Introduction: The incidence of pediatric nephrolithiasis has been increasing, and the role of genetic factors has garnered attention in recent years. This study aimed to explore the genetic basis underlying pediatric nephrolithiasis in Chinese population.

Methods: Whole exome sequencing (WES) was conducted in a consecutive cohort of 456 children over a 11-year period.

Phenotypic and genotypic characterization of familial adult myoclonus epilepsy in a Chinese case series.

Familial adult myoclonus epilepsy is a type of repeat expansion disorders caused by insertion of the causative pentanucleotide TTTCA repeat into an intronic polymorphic TTTTA repeat in different genes. We aimed to characterize the clinical features and elucidate the exact genetic basis of TTTTA/TTTCA repeat expansion in familial adult myoclonus epilepsy from mainland China. Eighty-five individuals including 36 patients and 49 normal phenotype relatives from seven pedigrees with familial adult myoclonus epilepsy, were recruited in a case series from mainland China.

Independent and joint air pollutants exposure associated with kidney dysfunction mediating by hematocyte.

Air pollution is associated with hyperuricemia; however, its underlying mechanism remains poorly understood. In this retrospective analysis, 233 anonymous health data and urban air pollutants data were obtained. The mean daily exposure dose (DED) for combined air pollutants (CAPs) was 1.

Protocol for isolating the single bacteriocyte from whiteflies for single-cell RNA-seq analysis.

Bacteriocytes are specialized insect cells adapted to harbor symbionts. However, their low number in individual whiteflies makes obtaining enough for transcriptome sequencing challenging. Here, we present a protocol for the isolation of whitefly bacteriocytes.

Generalizing Treatment Effect to a Target Population Without Individual Patient Data in a Real-World Setting.

The innovative use of real-world data (RWD) can answer questions that cannot be addressed using data from randomized clinical trials (RCTs). While the sponsors of RCTs have a central database containing all individual patient data (IPD) collected from trials, analysts of RWD face a challenge: regulations on patient privacy make access to IPD from all regions logistically prohibitive. In this research, we propose a double inverse probability weighting (DIPW) approach for the analysis sponsor to estimate the population average treatment effect (PATE) for a target population without the need to access IPD.

Rice BARENTSZ genes are required to maintain floral developmental stability against temperature fluctuations.

BARENTSZ (BTZ), a core component of the exon junction complex, regulates diverse developmental processes in animals. However, its evolutionary and developmental roles in plants remain elusive. Here, we revealed that three groups of paralogous BTZ genes existed in Poaceae, and Group 2 underwent loss-of-function mutations during evolution.

Two-stage stratified designs with survival outcomes and adjustment for misclassification in predictive biomarkers.

Biomarker stratified clinical trial designs are versatile tools to assess biomarker clinical utility and address its relationship with clinical endpoints. Due to imperfect assays and/or classification rules, biomarker status is prone to errors. To account for biomarker misclassification, we consider a two-stage stratified design for survival outcomes with an adjustment for misclassification in predictive biomarkers.

Regional consistency assessment in multiregional clinical trials.

Multiregional clinical trials (MRCTs) have become a favored strategy for new drug development. The accurate evaluation of treatment effects across different regions is crucial for interpreting the results of MRCTs. Consistency between regional and overall results ensures the extrapolability of the overall conclusions to individual regions.

The effect of STAT1, miR-99b, and MAP2K1 in alcoholic liver disease (ALD) mouse model and hepatocyte.

Alcoholic liver disease (ALD) serves as the leading cause of chronic liver diseases-related morbidity and mortality, which threatens the life of millions of patients in the world. However, the molecular mechanisms underlying ALD progression remain unclear. Here, we applied microarray analysis and experimental approaches to identify miRNAs and related regulatory signaling that associated with ALD.

Design and monitoring of clinical trials with an interim analysis and a negative binomial endpoint.

There are very rich publications devoted to group sequential design, adaptive design and trial monitoring for continuous, binary and time to event endpoints. Many authors also discuss fixed design, blinded sample size re-estimation design and group sequential design for studies with a negative binomial outcome. Nonetheless, literature is sparse in adaptive design for a trial with a negative binomial endpoint.

A case study: Assessing the efficacy of the revised dosage regimen via prediction model for recurrent event rate using biomarker data.

In recently conducted phase III trials in a rare disease area, patients received monthly treatment at a high dose of the drug, which targets to lower a specific biomarker level, closely associated with the efficacy endpoint, to around 10% across patients. Although this high dose demonstrated strong efficacy, treatments were withheld due to the reports of serious adverse events. Dosing in these studies were later resumed at a reduced dosage which targets to lower the biomarker level to 15%-35% across patients.

Expression Significance of Estrogen Receptor ER-α36 in Breast Cancer Treated by Chemotherapy: A Meta-Analysis.

Estrogen receptor (ER) is a molecular marker and target for diagnosing and treating breast cancer (BC). ER-α36, a novel estrogen receptor subtype, involved in the proliferation, differentiation, metastasis, and invasion of tumor cells. It is closely linked to the progression of various cancers.

Development and validation of a prognostic model for 90-day survival in patients with alcohol-associated cirrhosis and acute decompensation.

Background/purpose: Patients with alcohol-associated cirrhosis and acute decompensation are considered critically ill and have a higher risk of short-term mortality. This study aimed to establish a nomogram to evaluate their 90-day survival and identify factors that affect disease progression.

Methods: We included patients from September 2008 to December 2016 (n = 387 in the derivation group) and from January 2017 to August 2020 (n = 157 in the validation group).

End Group Engineering for Constructing A-D-A Fused-Ring Photosensitizers with Balanced Phototheranostics Performance.

Phototheranostics continues to flourish in cancer treatment. Due to the competitive relationships between these photophysical processes of fluorescence emission, photothermal conversion, and photodynamic action, it is critical to balance them through subtle photosensitizer designs. Herein, it is provided a useful guideline for constructing A-D-A photosensitizers with superior phototheranostics performance.

Mitochondria-Targeting Multimodal Phototheranostics Based on Triphenylphosphonium Cation Modified Amphiphilic Pillararenes and A-D-A Fused-Ring Photosensitizers.

Tumor-targeting phototheranostics has gradually developed as a powerful tool for the precise diagnosis and treatment of cancer. However, the designs of tumor-targeting phototheranostics agents with excellent multimodal phototherapy and fluorescence imaging (FLI) capability, as well as very few components, are still scarce and challenging for cancer treatment. Herein, a mitochondria-targeting multimodal phototheranostics system has been constructed by combining a designed amphiphilic pillararene WP5-2PEG-2TPP and the A-D-A fused-ring photosensitizer F8CA5.

Eliminating Ferroelectric Hysteresis in All-Two-Dimensional Gate-Stack Negative-Capacitance Transistors.

Boltzmann distribution thermal tails of carriers restrain the subthreshold swing (SS) of field-effect transistors (FETs) to be lower than 60 mV/decade at room temperature, which restrains the reduction of operate-voltage and power consumption of transistors. The negative-capacitance FET (NC FET) is expected to break through this physical limit and obtain a steep SS by amplifying the gate voltage through the negative capacitance effect of the ferroelectric thin film, providing a new way to further reduce the power consumption of the transistor at the end of Moore's law. Here, we show a MoS NC FET with a CuInPS ferroelectric, exhibiting a large on/off ratio of 10, a steep SS as low as 6 mV/decade, and a wide sub-60 mV/decade drain current range of more than 4 orders of magnitude while sacrificially inducing a huge hysteresis larger than 500 mV.

Bacterial, short-chain fatty acid and gas profiles of partially hydrolyzed guar gum in vitro fermentation by human fecal microbiota.

Carbohydrates with different structures have metabolic differences in the human body, as well as individual differences. The present study aimed to investigate the effects of bacterial, short-chain fatty acids (SCFAs) and gas profiles of partially hydrolyzed guar gum (PHGG) on the fecal microbiota of 41 Chinese individuals by simulated fermentation in vitro. Results showed that PHGG stimulated the growth of Bifidobacterium and Faecalibacterium, inhibited the growth of Escherichia-Shigella, Klebsiella, and Dorea, and induced the production of fermentation gases (CO2, and H2) and SCFAs (acetic acid, butyric acid).

Integrating Pillar[5]arene and BODIPY for a Supramolecular Nanoplatform To Achieve Synergistic Photodynamic Therapy and Chemotherapy.

BODIPY photosensitizers have been integrated with a hypoxia-activated prodrug to achieve synergistic photodynamic therapy (PDT) and chemotherapy. A novel BODIPY derivative BDP-CN was designed and synthesized. It had two cyano groups to make it complex well with a water-soluble pillar[5]arene.

Full-length transcriptome sequencing and transgenic tobacco revealed the key genes in the chlorogenic acid synthesis pathway of Sambucus chinensis L.

Chlorogenic acid is a key chemical in antioxidation and antisepsis. Sambucus chinensis L. is an herbaceous plant rich in chlorogenic acid and a potential genetic resource for breeding high-chlorogenic acid plants.

Utilization of treatment effect on a surrogate endpoint for planning a study to evaluate treatment effect on a final endpoint.

To design a phase III study with a final endpoint and calculate the required sample size for the desired probability of success, we need a good estimate of the treatment effect on the endpoint. It is prudent to fully utilize all available information including the historical and phase II information of the treatment as well as external data of the other treatments. It is not uncommon that a phase II study may use a surrogate endpoint as the primary endpoint and has no or limited data for the final endpoint.

Characterization of network hierarchy reflects cell state specificity in genome organization.

Dynamic chromatin structure acts as the regulator of transcription program in crucial processes including cancer and cell development, but a unified framework for characterizing chromatin structural evolution remains to be established. Here, we performed graph inferences on Hi-C data sets and derived the chromatin contact networks. We discovered significant decreases in information transmission efficiencies in chromatin of colorectal cancer (CRC) and T-cell acute lymphoblastic leukemia (T-ALL) compared to corresponding normal controls through graph statistics.