Aspartic acid residues in BBE-like enzymes from promote a function shift from oxidative cyclization to dehydrogenation.

Berberine bridge enzyme (BBE)-like enzymes catalyze various oxidative cyclization and dehydrogenation reactions in natural product biosynthesis, but the molecular mechanism underlying the selectivity remains unknown. Here, we elucidated the catalytic mechanism of BBE-like oxidases from involved in the oxidative cyclization and dehydrogenation of moracin C. X-ray crystal structures of a functionally promiscuous flavin adenine dinucleotide (FAD)-bound oxidase, MaDS1, with and without an oxidative dehydrogenation product were determined at 2.

Impact of early and delayed azvudine administration on COVID-19 mortality: a retrospective study.

Azvudine is recommended for patients with coronavirus disease 19 (COVID-19); however, its optimum therapeutic time window and its impact on mortality of patients are unclear. This single-centre, retrospective study from 1 November 2022 to 27 February 2023 conducted at the Peking Union Medical College Hospital was to discuss the dosing window of azvudine and compare the prognostic impact on COVID-19 patients of azvudine use within and after the defined time window. Therapeutic time window referred to the time interval between the onset of the disease and the drug administration.

Structural basis of auxin recognition and transport by the plant influx carrier AUX1.

Auxin regulates numerous aspects of plant growth and development, featuring polar auxin transport mediated by auxin efflux and influx carriers. AUX1 is the major auxin importer that actively takes up natural and synthetic auxins. However, the precise mechanisms underlying AUX1-mediated auxin recognition and transport remain elusive.

Structural Basis for Inhibition of Urate Reabsorption in URAT1.

The urate transporter 1 (URAT1) is the primary urate transporter in the kidney responsible for urate reabsorption and, therefore, is crucial for urate homeostasis. Hyperuricemia causes the common human disease gout and other pathological consequences. Inhibition of urate reabsorption through URAT1 has been shown as a promising strategy in alleviating hyperuricemia, and clinical and preclinical drug candidates targeting URAT1 are emerging.

Advances in macro-bioactive materials enhancing dentin bonding.

The long-term stability of dentin bonding is equally crucial for minimally invasive aesthetic restoration. Although the dentin bonding meets clinical standards at the initial stage, its long-term efficacy remains suboptimal owing to the impact of physiological factors. Herein, we present a comprehensive analysis of macro-bioactive materials, including nanomaterials and polymer materials, to improve the longevity of dentin bonding and extend the lifespan of adhesive prosthetics through various mechanisms to achieve sustained and stable dentin bonding effects over an extended period.

Lower respiratory tract microbiome is associated with checkpoint inhibitor pneumonitis in lung cancer patients.

Background: The gut microbiome is associated with the occurrence and severity of immune-related adverse events (irAEs) in cancer patients undergoing immunotherapy. However, the relationship between the lower respiratory tract (LRT) microbiome and checkpoint inhibitor pneumonitis (CIP) in lung cancer patients who underwent immunotherapy is unclear. The aim of the present study was to investigate the associations between the LRT microbiome and CIP in lung cancer patients receiving immunotherapy.

Longer duration of high-dose corticosteroids provides benefit for hospitalized COVID-19 patients with high oxygen requirement.

The optimal corticosteroids dose in patients with coronavirus disease 2019 (COVID-19) requiring high oxygen remains unknown. In this retrospective study of patients with COVID-19 requiring high oxygen and receiving corticosteroids, the efficacy, safety, and duration of high-dose treatment were evaluated. The primary outcome was all-cause mortality during follow-up.

Structure-guided discovery of bile acid derivatives for treating liver diseases without causing itch.

Chronic itch is a debilitating symptom profoundly impacting the quality of life in patients with liver diseases like cholestasis. Activation of the human G-protein coupled receptor, MRGPRX4 (hX4), by bile acids (BAs) is implicated in promoting cholestasis itch. However, the detailed underlying mechanisms remain elusive.

Effectiveness and safety of azvudine versus nirmatrelvir-ritonavir in adult patients infected with COVID-19 omicron strains: a retrospective study in Beijing.

The study was to evaluate the clinical outcomes of azvudine versus nirmatrelvir-ritonavir against omicron strains of coronavirus disease 2019 infections and determine their comparative effectiveness. This retrospective study included 716 patients who received nirmatrelvir-ritonavir (NR group) or azvudine (FNC group) at Peking Union Medical College Hospital between 1 November 2022 and 27 February 2023. Patients in the FNC group (n = 304) were younger, exhibited less severe symptoms, started antiviral therapy later, received corticosteroids more frequently, and used tocilizumab less frequently than patients in the NR group (n = 412).

Structural basis of TRPV1 inhibition by SAF312 and cholesterol.

Transient Receptor Potential Vanilloid 1 (TRPV1) plays a central role in pain sensation and is thus an attractive pharmacological drug target. SAF312 is a potent, selective, and non-competitive antagonist of TRPV1 and shows promising potential in treating ocular surface pain. However, the precise mechanism by which SAF312 inhibits TRPV1 remains poorly understood.

Application of a cloud platform that identifies patient-ventilator asynchrony and enables continuous monitoring of mechanical ventilation in intensive care unit.

Background: Patient-ventilator asynchrony (PVA) frequently occurs in mechanically ventilated patients within the ICU and has the potential for harm. Depending solely on the health care team cannot accurately and promptly identify PVA. To address this issue, our team has developed a cloud-based platform for monitoring mechanical ventilation (MV), comprising the PVA-RemoteMonitor system and the 24-h MV analysis report.

Structural Pharmacology of TRPV4 Antagonists.

The nonselective calcium-permeable Transient Receptor Potential Cation Channel Subfamily V Member4 (TRPV4) channel regulates various physiological activities. Dysfunction of TRPV4 is linked to many severe diseases, including edema, pain, gastrointestinal disorders, lung diseases, and inherited neurodegeneration. Emerging TRPV4 antagonists show potential clinical benefits.

The evolutionary origin of naturally occurring intermolecular Diels-Alderases from Morus alba.

Biosynthetic enzymes evolutionarily gain novel functions, thereby expanding the structural diversity of natural products to the benefit of host organisms. Diels-Alderases (DAs), functionally unique enzymes catalysing [4 + 2] cycloaddition reactions, have received considerable research interest. However, their evolutionary mechanisms remain obscure.

Enzymatic Degradation of Deoxynivalenol with the Engineered Detoxification Enzyme Fhb7.

In the era of global climate change, the increasingly severe head blight (FHB) and deoxynivalenol (DON) contamination have caused economic losses and brought food and feed safety concerns. Recently, an FHB resistance gene coding a glutathione-S transferase (GST) to degrade DON by opening the critical toxic epoxide moiety was identified and opened a new window for wheat breeding and DON detoxification. However, the poor stability of Fhb7 and the elusiveness of the catalytic mechanism hinder its practical application.

Potential molecular biomarkers for the diagnosis and prognosis of bladder cancer.

Bladder cancer (BC) is a common malignant tumor of urinary system, which can be divided into muscle-invasive BC (MIBC) and nonmuscle-invasive BC (NMIBC). The number of BC patients has been gradually increasing currently. At present, bladder tumours are diagnosed and followed-up using a combination of cystoscopic examination, cytology and histology.

Effectiveness of azvudine in reducing mortality of COVID-19 patients: a systematic review and meta-analysis.

Background: Azvudine has been approved for the treatment of coronavirus disease 2019 (COVID-19) patients in China, and this meta-analysis aims to illustrate the safety of azvudine and its effectiveness in reducing mortality.

Methods: PubMed, Embase, Web of science, Cochrane Library and the Epistemonikos COVID-19 Living Overview of Evidence database (L.OVE) were searched to aggregate currently published studies.

FeCoCuMnRuB Nanobox with Dual Driving of High-Entropy and Electron-Trap Effects as the Efficient Electrocatalyst for Water Oxidation.

High-entropy borides hold potential as electrocatalysts for water oxidation. However, the synthesis of the tailored nanostructures remains a challenge due to the thermodynamic immiscibility of polymetallic components. Herein, a FeCoCuMnRuB nanobox decorated with a nanosheet array was synthesized for the first time by a "coordination-etch-reduction" method.

Case report: Checkpoint inhibitor pneumonitis with positive anti-melanoma differentiation-associated gene 5 antibodies in a patient with lung cancer.

With the widespread use of immune checkpoint inhibitors to treat various cancers, pulmonary toxicity has become a topic of increasing concern. Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibodies are strongly associated with rapidly progressive interstitial lung disease (RP-ILD) in patients with clinically amyopathic dermatomyositis. However, anti-MDA5 antibody expression has not been reported in patients with immune-related adverse events.

Efficacy and safety of azvudine in symptomatic adult COVID-19 participants who are at increased risk of progressing to critical illness: a study protocol for a multicentre randomized double-blind placebo-controlled phase III trial.

Background: Severe acute respiratory syndrome coronavirus 2 will coexist with humans for a long time, and it is therefore important to develop effective treatments for coronavirus disease 2019 (COVID-19). Recent studies have demonstrated that antiviral therapy is a key factor in preventing patients from progressing to severe disease, even death. Effective and affordable antiviral medications are essential for disease treatment and are urgently needed.

Lack of CFAP54 causes primary ciliary dyskinesia in a mouse model and human patients.

Primary ciliary dyskinesia (PCD) is a highly heterogeneous recessive inherited disorder. FAP54, the homolog of CFAP54 in Chlamydomonas reinhardtii, was previously demonstrated as the C1d projection of the central microtubule apparatus of flagella. A Cfap54 knockout mouse model was then reported to have PCD-relevant phenotypes.

Gelatin-Functionalized Carbon Nanotubes Loaded with Cisplatin for Anti-Cancer Therapy.

Cisplatin (Cp), a chemotherapeutic agent, interacts with purines on tumor DNA, causing tumor cell apoptosis. However, cisplatin has the characteristics of non-specific distribution and lack of selectivity, resulting in systemic toxicity. Moreover, it cannot maintain the drug's high concentration in the tumor-weak acid environment.

Structural basis of human Slo2.2 channel gating and modulation.

The sodium-activated Slo2.2 channel is abundantly expressed in the brain, playing a critical role in regulating neuronal excitability. The Na-binding site and the underlying mechanisms of Na-dependent activation remain unclear.