Synergistic photobiocatalysis for enantioselective triple radical sorting.

Multicomponent reactions - those where three or more substrates combine into a product - have been highly useful in rapidly building chemical building blocks of increased complexity, but achieving this enzymatically has remained rare. This limitation primarily arises because an enzyme's active site is not typically set up to address multiple substrates, especially in cases involving multiple radical intermediates. Recently, chemical catalytic radical sorting has emerged as an enabling strategy for a variety of useful reactions.

In vitro antioxidant and protective effects of the extract of Broussonetia papyrifera leaves on imiquimod-induced skin lesions in psoriasis-like mice.

Psoriasis is a chronic inflammatory immune-related skin disease. According to literature reports, the leaves of Broussonetia papyrifera exhibit antioxidant, immune-enhancing and antibacterial effects. These leaves are not only used clinically for the treatment of superficial fungal infections and hepatitis, but also used in the development of health food.

CAZ Composite Photocatalysts for H Production and Degradation under Visible Light.

g-CN/Ag-ZnO (CAZ) composite photocatalysts were synthesized successfully by the hydrothermal method. The photocatalytic performance of photocatalysts was assessed through experiments measuring both hydrogen (H) production and the degradation of methylene blue (MB). The H production rate of 60% CAZ reached 2.

Modular Access to Chiral Amines via Imine Reductase-Based Photoenzymatic Catalysis.

The development of catalysts serves as the cornerstone of innovation in synthesis, as exemplified by the recent discovery of photoenzymes. However, the repertoire of naturally occurring enzymes repurposed by direct light excitation to catalyze new-to-nature photobiotransformations is currently limited to flavoproteins and keto-reductases. Herein, we shed light on imine reductases (IREDs) that catalyze the remote C(sp)-C(sp) bond formation, providing a previously elusive radical hydroalkylation of enamides for accessing chiral amines (45 examples with up to 99% enantiomeric excess).

Repurposing Visible-Light-Excited Ene-Reductases for Diastereo- and Enantioselective Lactones Synthesis.

Repurposing enzymes to catalyze non-natural asymmetric transformations that are difficult to achieve using traditional chemical methods is of significant importance. Although radical C-O bond formation has emerged as a powerful approach for constructing oxygen-containing compounds, controlling the stereochemistry poses a great challenge. Here we present the development of a dual bio-/photo-catalytic system comprising an ene-reductase and an organic dye for achieving stereoselective lactonizations.

Rare germline mutation and MSH2-&MSH6 + expression in a double primary carcinoma of colorectal carcinoma and endometrial carcinoma: a case report.

Background: Multiple primary malignancies are rare in cancer patients, and risk factors may include genetics, viral infection, smoking, radiation, and other environmental factors. Lynch syndrome (LS) is the most prevalent form of hereditary predisposition to double primary colorectal and endometrial cancer in females. LS, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is a common autosomal dominant condition.

A light-driven enzymatic enantioselective radical acylation.

Enzymes are recognized as exceptional catalysts for achieving high stereoselectivities, but their ability to control the reactivity and stereoinduction of free radicals lags behind that of chemical catalysts. Thiamine diphosphate (ThDP)-dependent enzymes are well-characterized systems that inspired the development of N-heterocyclic carbenes (NHCs) but have not yet been proved viable in asymmetric radical transformations. There is a lack of a biocompatible and general radical-generation mechanism, as nature prefers to avoid radicals that may be harmful to biological systems.

Regulation of intestinal micro ecology between raw and salt-processed Alpinia oxyphylla on renal injury rats.

Alpinia oxyphylla Fructus is one of the traditional Chinese medicine plants in the treatment of kidney injury. In clinical practice, crude Alpinia oxyphylla Fructus (CAOF) and salt-processed Alpinia oxyphylla Fructus (SAOF) are the two commonly used drugs specificated in the prevention and treatment of diabetic nephropathy (DN). However, the intestinal micro ecology regulation between CAOF and SAOF on DN has not been reported.

The Versatile Biocatalyst of Cytochrome P450 CYP102A1: Structure, Function, and Engineering.

Wild-type cytochrome P450 CYP102A1 from is a highly efficient monooxygenase for the oxidation of long-chain fatty acids. The unique features of CYP102A1, such as high catalytic activity, expression yield, regio- and stereoselectivity, and self-sufficiency in electron transfer as a fusion protein, afford the requirements for an ideal biocatalyst. In the past three decades, remarkable progress has been made in engineering CYP102A1 for applications in drug discovery, biosynthesis, and biotechnology.

Computational redesign of cytochrome P450 CYP102A1 for highly stereoselective omeprazole hydroxylation by UniDesign.

Cytochrome P450 CYP102A1 is a prototypic biocatalyst that has great potential in chemical synthesis, drug discovery, and biotechnology. CYP102A1 variants engineered by directed evolution and/or rational design are capable of catalyzing the oxidation of a wide range of organic compounds. However, it is difficult to foresee the outcome of engineering CYP102A1 for a compound of interest.

[Effect of body mass index on short-term effectiveness of high tibial osteotomy in treatment of varus knee arthritis].

Objective: To investigate the effect of body mass index (BMI) on the short-term effectiveness of high tibial osteotomy (HTO) in the treatment of varus knee arthritis.

Methods: The clinical data of 84 patients (84 knees) with varus knee arthritis treated with HTO between May 2016 and August 2020 were retrospectively analyzed. According to BMI, the patients were divided into normal group (32 patients in group A, BMI<25 kg/m ), overweight group (27 patients in group B, BMI>30 kg/m ), and obese group (25 patients in group C, BMI>30 kg/m ).

A ubiquitination-mediated degradation system to target 14-3-3-binding phosphoproteins.

The phosphorylation of 14-3-3 binding motif is involved in many cellular processes. A strategy that enables targeted degradation of 14-3-3-binding phosphoproteins (14-3-3-BPPs) for studying their functions is highly desirable for basic research. Here, we report a phosphorylation-induced, ubiquitin-proteasome-system-mediated targeted protein degradation (TPD) strategy that allows specific degradation of 14-3-3-BPPs.

Network pharmacological analysis to reveal the mechanism governing the effect of Qin Xi Tong on osteoarthritis and rheumatoid arthritis.

Introduction: Qin Xi Tong (QXT), produced by water extracts of Caulis Sinomenii, is clinically effective in the therapy of rheumatoid arthritis (RA). It is also a complementary agent for osteoarthritis (OA). This study aimed to screen the candidate targets and identify the potential mechanisms of QXT against RA and OA.

Decoding CRISPR-Cas PAM recognition with UniDesign.

The critical first step in Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated (CRISPR-Cas) protein-mediated gene editing is recognizing a preferred protospacer adjacent motif (PAM) on target DNAs by the protein's PAM-interacting amino acids (PIAAs). Thus, accurate computational modeling of PAM recognition is useful in assisting CRISPR-Cas engineering to relax or tighten PAM requirements for subsequent applications. Here, we describe a universal computational protein design framework (UniDesign) for designing protein-nucleic acid interactions.

Metaflammation in glucolipid metabolic disorders: Pathogenesis and treatment.

The public health issue of glucolipid metabolic disorders (GLMD) has grown significantly, posing a grave threat to human wellness. Its prevalence is rising yearly and tends to affect younger people. Metaflammation is an important mechanism regulating body metabolism.

Establishing an RNA fusions panel in soft tissue sarcoma with clinical validation.

The diagnosis and classification of soft tissue sarcomas (STS) remain challenging because of the rarity and overlapping morphologic manifestations of diverse STS subtypes. Characteristic gene fusions are commonly detected in STS and represent useful diagnostic markers. This study established and validated a custom-designed RNA sequencing panel that identified 64 gene fusions in STS.

Application of machine learning in Chinese medicine differentiation of dampness-heat pattern in patients with type 2 diabetes mellitus.

Background: China has become the country with the largest number of people with type 2 diabetes mellitus (T2DM), and Chinese medicine (CM) has unique advantages in preventing and treating T2DM, while accurate pattern differentiation is the guarantee for proper treatment.

Objective: The establishment of the CM pattern differentiation model of T2DM is helpful to the pattern diagnosis of the disease. At present, there are few studies on dampness-heat pattern differentiation models of T2DM.

[Risk factors for osteonecrosis of femoral head after femoral neck fracture fixation with femoral neck system].

Objective: To explore the risk factors for osteonecrosis of the femoral head (ONFH) after treatment of femoral neck fractures with femoral neck system (FNS).

Methods: Between January 2020 and February 2021, 179 patients (182 hips) with femoral neck fractures treated by FNS fixation were selected for retrospective analysis. There were 96 males and 83 females with an average age of 53.

De novo protein fold design through sequence-independent fragment assembly simulations.

De novo protein design generally consists of two steps, including structure and sequence design. Many protein design studies have focused on sequence design with scaffolds adapted from native structures in the PDB, which renders novel areas of protein structure and function space unexplored. We developed FoldDesign to create novel protein folds from specific secondary structure (SS) assignments through sequence-independent replica-exchange Monte Carlo (REMC) simulations.

[Research progress of femoral neck system in treatment of femoral neck fracture in young and middle-aged patients].

Objective: To summarize the research progress of femoral neck system (FNS) in the treatment of femoral neck fracture in young and middle-aged patients.

Methods: The literature on FNS at home and abroad in recent years was extensively reviewed, and the results of mechanical and clinical studies on FNS were summarized based on clinical experience.

Results: FNS has good mechanical stability, which can reduce complications such as femoral neck shortening, internal fixation failure, and varus caused by mechanical instability.

Current Status and Factors Associated with Clean Operating Rooms: A Survey of Hospitals in China.

Background: Indoor air quality is controlled in the clean operating room (OR) to reduce the risk of surgical-site infections (SSIs). The aim of this study is to assess the usage and management of clean ORs in China and to identify factors associated with the risk of SSIs.

Methods: An online survey was distributed to hospitals in China from August 5 to September 5, 2018 via the WeChat account of the Shanghai International Forum for Infection Control and Prevention.

Recent Advances in Improving Gene-Editing Specificity through CRISPR-Cas9 Nuclease Engineering.

CRISPR-Cas9 is the state-of-the-art programmable genome-editing tool widely used in many areas. For safe therapeutic applications in clinical medicine, its off-target effect must be dramatically minimized. In recent years, extensive studies have been conducted to improve the gene-editing specificity of the most popular CRISPR-Cas9 nucleases using different strategies.