The spatiotemporal transcriptional profiling of murine brain during cerebral malaria progression and after artemisinin treatment.

Cerebral malaria (CM) is a severe encephalopathy caused by Plasmodium parasite infection, resulting in thousands of annual deaths and neuro-cognitive sequelae even after anti-malarial drugs treatment. Despite efforts to dissect the mechanism, the cellular transcriptomic reprogramming within the spatial context remains elusive. Here, we constructed single-cell and spatial transcriptome atlases of experimental CM (ECM) male murine brain tissues with or without artesunate (ART) treatment.

Activity-based chemical proteomics reveals caffeic acid ameliorates pentylenetetrazol-induced seizures by covalently targeting aconitate decarboxylase 1.

Background: Epilepsy is a neurological disorder characterized by recurrent seizures, tightly associated with neuroinflammation. Activation of inflammatory cells and molecules in damaged nervous tissues plays a pivotal role in epilepsy. Caffeic acid, one of the most abundant polyphenols in coffee, has shown potent protective effects as a phytomedicine in various neurological disorders.

SNHG17 Reprograms Energy Metabolism of Breast Cancer by Activating Mitochondrial DNA Transcription.

In most solid tumors, cellular energy metabolism is primarily dominated by aerobic glycolysis, which fulfills the high demand for biomacromolecules at the expense of reduced ATP production efficiency. Elucidation of the mechanisms by which rapidly proliferating malignant cells acquire sufficient energy in this state of inefficient ATP production from glycolysis could enable the development of metabolism-targeted therapeutic strategies. In this study, we observed a significant association between elevated expression levels of the long noncoding RNA small nuclear RNA host gene 17 (SNHG17) and unfavorable prognosis in breast cancer.

A primitive cell model involving Vesicles, microtubules and asters.

Hypothesis: Simple single-chain amphiphiles (sodium monododecyl phosphate, SDP) and organic small molecules (isopentenol, IPN), both of primitive relevance, are proved to have been the building blocks of protocells on the early Earth. How do SDP-based membrane and coexisting IPN come together in specific ways to produce more complex chemical entities? What kind of cell-like behavior can be endowed with this protocell model? These are important questions in the pre-life chemical origin scenario that have not been answered to date.

Experiments: The phase behavior and formation mechanism of the aggregates for SDP/IPN/HO ternary system were characterized and studied by different electron microscopy, fluorescent probe technology, DLS, IR, ESI-MS, SAXS, etc.

A distinct subset of urothelial cells with enhanced EMT features promotes chemotherapy resistance and cancer recurrence by increasing COL4A1-ITGB1 mediated angiogenesis.

Drug resistance and tumor recurrence remain clinical challenges in the treatment of urothelial carcinoma (UC). However, the underlying mechanism is not fully understood. Here, we performed single-cell RNA sequencing and identified a subset of urothelial cells with epithelial-mesenchymal transition (EMT) features (EMT-UC), which is significantly correlated with chemotherapy resistance and cancer recurrence.

Off-the-shelf CAR-NK cells targeting immunogenic cell death marker ERp57 execute robust antitumor activity and have a synergistic effect with ICD inducer oxaliplatin.

Background: Chimeric antigen receptor natural killer (CAR-NK) therapy holds great promise for treating hematologic tumors, but its efficacy in solid tumors is limited owing to the lack of suitable targets and poor infiltration of engineered NK cells. Here, we explore whether immunogenic cell death (ICD) marker ERp57 translocated from endoplasmic reticulum to cell surface after drug treatment could be used as a target for CAR-NK therapy.

Methods: To target ERp57, a VHH phage display library was used for screening ERp57-targeted nanobodies (Nbs).

Long term rescue of Alzheimer's deficits by one-time gene-editing of C-terminus.

Gene-editing technologies promise to create a new class of therapeutics that can achieve permanent correction with a single intervention. Besides eliminating mutant alleles in familial disease, gene-editing can also be used to favorably manipulate upstream pathophysiologic events and alter disease-course in wider patient populations, but few such feasible therapeutic avenues have been reported. Here we use CRISPR-Cas9 to edit the last exon of amyloid precursor protein ( ), relevant for Alzheimer's disease (AD).

A Fusion-Growth Protocell Model Based on Vesicle Interactions with Pyrite Particles.

Protocell models play a pivotal role in the exploration of the origin of life. Vesicles are one type of protocell model that have attracted much attention. Simple single-chain amphiphiles (SACs) and organic small molecules (OSMs) possess primitive relevance and were most likely the building blocks of protocells on the early Earth.

Revealing the drivers and genesis of NO-N pollution classification in shallow groundwater of the Shaying River Basin by explainable machine learning and pathway analysis method.

Nitrate (NO-N), as one of the ubiquitous contaminants in groundwater worldwide, has posed a serious threat to public health and the ecological environment. Despite extensive research on its genesis, little is known about the differences in the genesis of NO-N pollution across different concentrations. Herein, a study of NO-N pollution concentration classification was conducted using the Shaying River Basin as a typical area, followed by examining the genesis differences across different pollution classifications.

Dopamine modification of glycolytic enzymes impairs glycolysis: possible implications for Parkinson's disease.

Background: Parkinson's disease (PD), a chronic and severe neurodegenerative disease, is pathologically characterized by the selective loss of nigrostriatal dopaminergic neurons. Dopamine (DA), the neurotransmitter produced by dopaminergic neurons, and its metabolites can covalently modify proteins, and dysregulation of this process has been implicated in neuronal loss in PD. However, much remains unknown about the protein targets.

The PD-1- and LAG-3-targeting bispecific molecule tebotelimab in solid tumors and hematologic cancers: a phase 1 trial.

Tebotelimab, a bispecific PD-1×LAG-3 DART molecule that blocks both PD-1 and LAG-3, was investigated for clinical safety and activity in a phase 1 dose-escalation and cohort-expansion clinical trial in patients with solid tumors or hematologic malignancies and disease progression on previous treatment. Primary endpoints were safety and maximum tolerated dose of tebotelimab when administered as a single agent (n = 269) or in combination with the anti-HER2 antibody margetuximab (n = 84). Secondary endpoints included anti-tumor activity.

Multifunctional nanozyme-reinforced copper-coordination polymer nanoparticles for drug-resistance bacteria extinction and diabetic wound healing.

Background: Drug-resistant bacterial infections in chronic wounds are a persistent issue, as they are resistant to antibiotics and can cause excessive inflammation due to generation of reactive oxygen species (ROS). An effective solution would be to not only combat bacterial infections but also scavenge ROS to relieve inflammation at the wound site. Scaffolds with antioxidant properties are attractive for their ability to scavenge ROS, and there is medical demand in developing antioxidant enzyme-mimicking nanomaterials for wound healing.

Betaxolol as a Potent Inhibitor of NDM-1-Positive That Synergistically Enhances the Anti-Inflammatory Effect in Combination with Meropenem.

With significant human and economic losses, increasing bacterial resistance is a serious global threat to human life. Due to their high efficacy, broad spectrum, and cost-effectiveness, beta-lactams are widely used in the clinical management of bacterial infection. The emergence and wide spread of New Delhi metallo-β-lactamase (NDM-1), which can effectively inactivate β-lactams, has posed a challenge in the design of effective new antimicrobial treatments.

Effect and genesis of soil nitrogen loading and hydrogeological conditions on the distribution of shallow groundwater nitrogen pollution in the North China Plain.

The North China Plain (NCP) has experienced increasingly severe groundwater nitrogen (TN) pollution. However, the factors influencing TN distribution are still poorly understood. Previous studies have identified surface soil nitrogen (TSN) loading and intrinsic groundwater vulnerability (Inv) as the main factors controlling groundwater TN pollution.

Novel Insight into Functions of Transcription Factor EB (TFEB) in Alzheimer's Disease and Parkinson's Disease.

A key pathological feature of neurodegenerative diseases (NDs) such as Alzheimer's disease (AD) and Parkinson's disease (PD) is the accumulation of aggregated and misfolded protein aggregates with limited effective therapeutic agents. TFEB (transcription factor EB), a key regulator of lysosomal biogenesis and autophagy, plays a pivotal role in the degradation of protein aggregates and has thus been regarded as a promising therapeutic target for these NDs. Here, we systematically summarize the molecular mechanisms and function of TFEB regulation.

Circulating Tumor DNA as a Predictive Biomarker for Clinical Outcomes With Margetuximab and Pembrolizumab in Pretreated HER2-Positive Gastric/ Gastroesophageal Adenocarcinoma.

Purpose: To assess the ability of circulating tumor DNA (ctDNA)-based testing to identify patients with HER2 (encoded by ERBB2)-positive gastric/gastroesophageal adenocarcinoma (GEA) who progressed on or after trastuzumab-containing treatments were treated with combination therapy of anti-HER2 and anti-PD-1 agents.

Methods: ctDNA analysis was performed retrospectively using plasma samples collected at study entry from 86 patients participating in the phase 1/2 CP-MGAH22-05 study (NCT02689284).

Results: Objective response rate (ORR) was significantly higher in evaluable ERBB2 amplification-positive vs - negative patients based on ctDNA analysis at study entry (37% vs 6%, respectively; P = .

The activity and mechanism of vidofludimus as a potent enzyme inhibitor against NDM-1-positive E. coli.

New Delhi metallo-β-lactamase-1 (NDM-1) is the most important and prevalent enzyme among all metallo-β-lactamases. NDM-1 can hydrolyze almost all-available β-lactam antibiotics including carbapenems, resulting in multidrug resistance, which poses an increasing clinical threat. However, there is no NDM-1 inhibitor approved for clinical treatment.

Single-cell transcriptome analysis reveals liver injury induced by glyphosate in mice.

Background: Glyphosate (GLY), as the active ingredient of the most widely used herbicide worldwide, is commonly detected in the environment and living organisms, including humans. Its toxicity and carcinogenicity in mammals remain controversial. Several studies have demonstrated the hepatotoxicity of GLY; however, the underlying cellular and molecular mechanisms are still largely unknown.

Energy supply and influencing factors of mountain marathon runners from Baiyin marathon accident in China.

High temperature impacts the performance of marathon athletes, and hypothermia harms athletes. Twenty-one runners died, and eight were injured in the China Baiyin marathon on May 22, 2021. It's a typical human life test.

Coupling of multi-hydrochemical and statistical methods for identifying apparent background levels of major components and anthropogenic anomalous activities in shallow groundwater of the Liujiang Basin, China.

Natural background levels (NBLs) is a prerequisite for distinguishing anthropogenic groundwater pollution and judging the evolution of groundwater quality. However, due to regional differences of hydrogeochemitry and water-rock interaction, coupled with long-term anthropogenic activities, it is no longer accurate to assess NBLs with only statistical methods or without considering human impact. Herein, multi-hydrochemical and statistical methods were examined to identify apparent background levels and anthropogenic anomalous activities of shallow groundwater by selecting Liujiang Basin as a study area.

Impairment of the autophagy-lysosomal pathway in Alzheimer's diseases: Pathogenic mechanisms and therapeutic potential.

Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by memory loss and cognitive dysfunction. The accumulation of misfolded protein aggregates including amyloid beta (A) peptides and microtubule associated protein tau (MAPT/tau) in neuronal cells are hallmarks of AD. So far, the exact underlying mechanisms for the aetiologies of AD have not been fully understood and the effective treatment for AD is limited.

Quantifying the Effect of Public Activity Intervention Policies on COVID-19 Pandemic Containment Using Epidemiologic Data From 145 Countries.

Objectives: Most countries have adopted public activity intervention policies to control the coronavirus disease 2019 (COVID-19) pandemic. Nevertheless, empirical evidence of the effectiveness of different interventions on the containment of the epidemic was inconsistent.

Methods: We retrieved time-series intervention policy data for 145 countries from the Oxford COVID-19 Government Response Tracker from December 31, 2019, to July 1, 2020, which included 8 containment and closure policies.