Melatonin promotes cell cycle progression of neural stem cells subjected to manganese via Nurr1.

Excessive exposure to manganese (Mn) through drinking water and food during pregnancy significantly heightens the likelihood of neurodevelopmental damage in offspring. Multiple studies have indicated that melatonin (Mel) may help to relieve neurodevelopmental disorders caused by Mn, but potential mechanisms underlying this effect require further exploration. Here, we utilized primary neural stem cells (NSCs) as a model to elucidate the molecular mechanism underlying the protective function of Mel on Mn-induced cell proliferation dysfunction and cycle arrest. Our results showed that Mn disrupted the cell cycle in NSCs by suppressing positive regulatory proteins (CDK2, Cyclin A, Cyclin D1, and E2F1) and enhancing negative ones (p27KIP1 and p57KIP2), leading to cell proliferation dysfunction. Mel inhibited the Mn-dependent changes to these proteins and the cell cycle through nuclear receptor-related protein 1 (Nurr1), thus alleviating the proliferation dysfunction. Knockdown of Nurr1 using lentivirus-expressed shRNA in NSCs resulted in a diminished protective effect of Mel. We concluded that Mel mitigated Mn-induced proliferation dysfunction and cycle arrest in NSCs through Nurr1.

GETdb: A comprehensive database for genetic and evolutionary features of drug targets.

The development of an innovative drug is complex and time-consuming, and the drug target identification is one of the critical steps in drug discovery process. Effective and accurate identification of drug targets can accelerate the drug development process. According to previous research, evolutionary and genetic information of genes has been found to facilitate the identification of approved drug targets. In addition, allosteric proteins have great potential as targets due to their structural diversity. However, this information that could facilitate target identification has not been collated in existing drug target databases. Here, we construct a comprehensive drug target database named Genetic and Evolutionary features of drug Targets database (GETdb, http://zhanglab.hzau.edu.cn/GETdb/page/index.jsp). This database not only integrates and standardizes data from dozens of commonly used drug and target databases, but also innovatively includes the genetic and evolutionary information of targets. Moreover, this database features an effective allosteric protein prediction model. GETdb contains approximately 4000 targets and over 29,000 drugs, and is a user-friendly database for searching, browsing and downloading data to facilitate the development of novel targets.

Extrusion Printing of Surface-Functionalized Metal-Organic Framework Inks for a High-Performance Wearable Volatile Organic Compound Sensor.

Wearable sensors hold immense potential for real-time and non-destructive sensing of volatile organic compounds (VOCs), requiring both efficient sensing performance and robust mechanical properties. However, conventional colorimetric sensor arrays, acting as artificial olfactory systems for highly selective VOC profiling, often fail to meet these requirements simultaneously. Here, a high-performance wearable sensor array for VOC visual detection is proposed by extrusion printing of hybrid inks containing surface-functionalized sensing materials. Surface-modified hydrophobic polydimethylsiloxane (PDMS) improves the humidity resistance and VOC sensitivity of PDMS-coated dye/metal-organic frameworks (MOFs) composites. It also enhances their dispersion within liquid PDMS matrix, thereby promoting the hybrid liquid as high-quality extrusion-printing inks. The inks enable direct and precise printing on diverse substrates, forming a uniform and high particle-loading (70 wt%) film. The printed film on a flexible PDMS substrate demonstrates satisfactory flexibility and stretchability while retaining excellent sensing performance from dye/MOFs@PDMS particles. Further, the printed sensor array exhibits enhanced sensitivity to sub-ppm VOC levels, remarkable resistance to high relative humidity (RH) of 90%, and the differentiation ability for eight distinct VOCs. Finally, the wearable sensor proves practical by in situ monitoring of wheat scab-related VOC biomarkers. This study presents a versatile strategy for designing effective wearable gas sensors with widespread applications.

Identification of Treg-related prognostic molecular subtypes and individualized characteristics in clear cell renal cell carcinoma through single-cell transcriptomes and bulk RNA sequencing.

BACKGROUND: In clear cell renal cell carcinoma (ccRCC), the role of Regulatory T cells (Treg cells) as prognostic and immunotherapy response predictors is not fully explored. METHODS: Analyzing renal clear cell carcinoma datasets from TISCH, TCGA, and GEO, we focused on 8 prognostic Treg genes to study patient subtypes in ccRCC. We assessed Treg subtypes in relation to patient prognosis, tumor microenvironment, metabolism. Using Cox regression and principal component analysis, we devised Treg scores for individual patient characterization and explored the molecular role of C1QL1, a critical gene in the Treg model, through in vivo and in vitro studies. RESULTS: Eight Treg-associated prognostic genes were identified, classifying ccRCC patients into cluster A and B. Cluster A patients showed poorer prognosis with distinct clinical and molecular profiles, potentially benefiting more from immunotherapy. Low Treg scores correlated with worse outcomes and clinical progression. Low scores also suggested that patients might respond better to immunotherapy and targeted therapies. In ccRCC, C1QL1 knockdown reduced tumor proliferation and invasion via NF-kb-EMT pathways and decreased Treg cell infiltration, enhancing immune efficacy. CONCLUSIONS: The molecular subtype and Treg score in ccRCC, based on Treg cell marker genes, are crucial in personalizing ccRCC treatment and underscore C1QL1's potential as a tumor biomarker and target for immunotherapy.

MRI quantitative assessment of the effects of low-carbohydrate therapy on Hashimoto's thyroiditis.

Objective: Hashimoto's thyroiditis is an inflammatory disease, and research suggests that a low-carbohydrate diet may have potential anti-inflammatory effects. This study aims to utilize Dixon-T2-weighted imaging (WI) sequence for a semi-quantitative assessment of the impact of a low-carbohydrate diet on the degree of thyroid inflammation in patients with Hashimoto's thyroiditis. Methods: Forty patients with Hashimoto's thyroiditis were recruited for this study and randomly divided into two groups: one with a normal diet and the other with a low-carbohydrate diet. Antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) were measured for all participants. Additionally, thyroid water content was semi-quantitatively measured using Dixon-T2WI. The same tests and measurements were repeated for all participants after 6 months. Results: After 6 months of a low-carbohydrate diet, patients with Hashimoto's thyroiditis showed a significant reduction in thyroid water content (94.84 ± 1.57% vs 93.07 ± 2.05%, P < 0.05). Concurrently, a decrease was observed in levels of TPOAb and TgAb (TPOAb: 211.30 (92.63-614.62) vs 89.45 (15.9-215.67); TgAb: 17.05 (1.47-81.64) vs 4.1 (0.51-19.42), P < 0.05). In contrast, there were no significant differences in thyroid water content or TPOAb and TgAb levels for patients with Hashimoto's thyroiditis following a normal diet after 6 months (P < 0.05). Conclusion: Dixon-T2WI can quantitatively assess the degree of thyroid inflammation in patients with Hashimoto's thyroiditis. Following a low-carbohydrate diet intervention, there is a significant reduction in thyroid water content and a decrease in levels of TPOAb and TgAb. These results suggest that a low-carbohydrate diet may help alleviate inflammation in patients with Hashimoto's thyroiditis.

Short-term effects of a new resistance exercise approach on physical function during chemotherapy after radical breast cancer surgery: a randomized controlled trial.

BACKGROUND: Approximately 30% of post-operative breast cancer patients develop shoulder joint movement disorders affecting routine upper limb movement. This study discusses the impact of a neuromuscular joint facilitation (NJF) method on the physical function of breast cancer patients experiencing shoulder dysfunction during chemotherapy after radical surgery. METHODS: This study included 162 female patients who have unilateral breast cancer in a cancer hospital in China. They developed shoulder joint mobility disorders during chemotherapy within 1-3 months postoperatively. These patients were divided into three groups: NJF, conventional rehabilitation (conventional group), and control groups. The clinical examination included the maximum passive and active range of motion (ROM) of the shoulder (flexion, extension, abduction, adduction, and external and internal rotation). Other evaluations included a pain score using a visual analog scale (VAS), grip strength, and supraspinatus muscle thickness. All tests were evaluated pre-and post-intervention. RESULTS: The NJF group showed a significant increase in all shoulder ROM angles post-intervention. In the conventional group, all other ROM values increased significantly, except passive external rotation ROM. In the control group, all other ROM values increased significantly, except passive and active external rotation ROM. All three groups had decreased VAS scores, increased grip strength, and supraspinatus muscle thickness post-intervention during active abduction. In the control group, the supraspinatus contraction rate decreased significantly at 60° and 90° abduction post-intervention compared to that at pre-intervention. CONCLUSION: This study revealed that NJF during chemotherapy had positive clinical intervention effects, improving shoulder joint mobility disorders, pain, grip strength, and external rotation following radical breast cancer surgery. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry; https://www.chictr.org.cn/ (ChiCTR2300073170), registered (03/07/2023).

Controlled Assembly and Disassembly of Higher-Order Peptide Nanotubes.

The controlled peptide self-assembly and disassembly are not only implicated in many cellular processes but also possess huge application potential in a wide range of biotechnology and biomedicine. ß-sheet peptide assemblies possess high kinetic stability, so it is usually hard to disassemble them rapidly. Here, we reported that both the self-assembly and disassembly of a designed short ß-sheet peptide IIIGGHK could be well harnessed through the variations of concentration, pH, and mechanical stirring. Microscopic imaging, neutron scattering, and infrared spectroscopy were used to track the assembly and disassembly processes upon these stimuli, especially the interconversion between thin, left-handed protofibrils and higher-order nanotubes with superstructural right-handedness. The underlying rationale for these controlled disassembly processes mainly lies in the fact that the specific His-His interactions between protofibrils were responsive to these stimuli. By taking advantage of the peptide self-assembly and disassembly, the encapsulation of the hydrophobic drug curcumin and its rapid release upon stimuli were achieved. Additionally, the peptide hydrogels facilitated the differentiation of neural cells while maintaining low cell cytotoxicity. We believe that such dynamic and reversible structural transformation in this work provides a distinctive paradigm for controlling the peptide self-assembly and disassembly, thus laying a foundation for practical applications of peptide assemblies.

Skin lightening properties of zerumbone cream: A placebo-controlled study.

OBJECTIVE: Despite the demonstrated anti-melanogenic and UV protective effects of Zerumbone (ZER) in vitro, there is a lack of clinical trials that have been done to assess these properties. The primary objective of this study was to assess the effectiveness of ZER in lightening the skin tone of human participants with a single-blind approach. METHODS: Twenty-six participants were randomly assigned to two groups to investigate the application location (left or right volar forearm) for the placebo and ZER creams. Both creams were topically administered to the volar forearms twice daily over a duration of 4 weeks. Initial skin irritation was assessed before and 30 min after applying creams. The melanin and erythema levels were quantified with Mexameter MX 18. RESULTS: Twenty participants were included in the analysis. The cream formulation had excellent physical properties and was well-received by the participants. The initial skin irritation study results indicated that neither of the creams elicited an allergic reaction. The administration of ZER cream resulted in a statistically significant reduction in melanin levels (p < 0.05) after 1 week compared to the initial baseline. Furthermore, after 2 weeks of application, ZER cream demonstrated significant differences in melanin levels compared to placebo (p < 0.05). No adverse effects were observed in the group using ZER cream. CONCLUSION: ZER demonstrated significant potential as a skin-lightening agent.

Cognitive impairment in Alzheimer's disease FAD4T mouse model: Synaptic loss facilitated by activated microglia via C1qA.

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder characterized by cognitive dysfunction. The connection between neuroinflammation and abnormal synaptic function in AD is recognized, but the underlying mechanisms remain unclear. In this study, we utilized a mouse model of AD, FAD4T mice aged 6-7 months, to investigate the molecular changes affecting cognitive impairment. Behavior tests showed that FAD4T mice exhibited impaired spatial memory compared with their wild-type littermates. Immunofluorescence staining revealed the presence of Aß plaques and abnormal glial cell activation as well as changes in microglial morphology in the cortex and hippocampus of FAD4T mice. Synaptic function was impaired in FAD4T mice. Patch clamp recordings of hippocampal neurons revealed reduced amplitude of miniature excitatory postsynaptic currents. Additionally, Golgi staining showed decreased dendritic spine density in the cortex and hippocampus of FAD4T mice, indicating aberrant synapse morphology. Moreover, hippocampal PSD-95 and NMDAR1 protein levels decreased in FAD4T mice. RNA-seq analysis revealed elevated expression of immune system and proinflammatory genes, including increased C1qA protein and mRNA levels, as well as higher expression of TNF-α and IL-18. Taken together, our findings suggest that excessive microglia activation mediated by complement factor C1qA may contribute to aberrant synaptic pruning, resulting in synapse loss and disrupted synaptic transmission, ultimately leading to AD pathogenesis and behavioral impairments in the FAD4T mouse model. Our study provides valuable insights into the underlying mechanisms of cognitive impairments and preliminarily explores a potentially effective treatment approach targeting on C1qA for AD.

Reliability and Validity of the Star Excursion Balance Test for Evaluating Dynamic Balance of Upper Extremities.

BACKGROUND: Upper extremity (UE) dynamic balance is a significant physical fitness ability, which includes high-level neuromuscular proprioception, joint mobility, force, and coordination. The evaluation methods of UE dynamic balance are insufficient and lack experimental support. The Star Excursion Balance Test (SEBT) is a reliable assessment of dynamic balance and injury risk of the lower extremity. HYPOTHESIS: The UE-SEBT is a reliable and reproducible approach for evaluating dynamic balance of UEs. STUDY DESIGN: Observational study. LEVEL OF EVIDENCE: Level 4. METHODS: This cross-sectional study recruited 65 healthy adults. All participants were required to complete UE-SEBT, UE Y-balance test (UE-YBT), maximal voluntary isometric contraction (MVIC) of UE, closed kinetic chain UE stability test (CKCUEST), trunk flexor endurance test (TFET), trunk extensor endurance test (TEET), and lateral trunk endurance test (LTET). Intra- and inter-rater reliability and the correlation of UE-SEBT with other outcomes were measured. RESULTS: Among the participants, the intra- and interoperator reliability of UE-SEBT in all directions and composite score achieved a moderate-to-excellent (intraclass correlation coefficients [ICC], 0.729-0.946) reliability. For validity, the UE-SEBT had a moderate to very strong correlation with UE-YBT (r = 0.315-0.755, P < 0.01) and a strong correlation with CKCUEST (r = 0.4-0.67, P < 0.01). Furthermore, the UE-SEBT performance showed weak-to-strong correlations with MVIC (r = 0.26-0.43, P < 0.05). UE-SEBT was also correlated with LTET, TEET, and TFET to varying degrees. CONCLUSION: UE-SEBT has good reliability and validity to assess UE dynamic balance compared with other tests. CLINICAL RELEVANCE: UE-SEBT can be used as a clinical assessment method to evaluate UE dynamic balance and injury prevention.

MI-DenseCFNet: deep learning-based multimodal diagnosis models for Aureus and Aspergillus pneumonia.

OBJECTIVE: To build and merge a diagnostic model called multi-input DenseNet fused with clinical features (MI-DenseCFNet) for discriminating between Staphylococcus aureus pneumonia (SAP) and Aspergillus pneumonia (ASP) and to evaluate the significant correlation of each clinical feature in determining these two types of pneumonia using a random forest dichotomous diagnosis model. This will enhance diagnostic accuracy and efficiency in distinguishing between SAP and ASP. METHODS: In this study, 60 patients with clinically confirmed SAP and ASP, who were admitted to four large tertiary hospitals in Kunming, China, were included. Thoracic high-resolution CT lung windows of all patients were extracted from the picture archiving and communication system, and the corresponding clinical data of each patient were collected. RESULTS: The MI-DenseCFNet diagnosis model demonstrates an internal validation set with an area under the curve (AUC) of 0.92. Its external validation set demonstrates an AUC of 0.83. The model requires only 10.24s to generate a categorical diagnosis and produce results from 20 cases of data. Compared with high-, mid-, and low-ranking radiologists, the model achieves accuracies of 78% vs. 75% vs. 60% vs. 40%. Eleven significant clinical features were screened by the random forest dichotomous diagnosis model. CONCLUSION: The MI-DenseCFNet multimodal diagnosis model can effectively diagnose SAP and ASP, and its diagnostic performance significantly exceeds that of junior radiologists. The 11 important clinical features were screened in the constructed random forest dichotomous diagnostic model, providing a reference for clinicians. CLINICAL RELEVANCE STATEMENT: MI-DenseCFNet could provide diagnostic assistance for primary hospitals that do not have advanced radiologists, enabling patients with suspected infections like Staphylococcus aureus pneumonia or Aspergillus pneumonia to receive a quicker diagnosis and cut down on the abuse of antibiotics. KEY POINTS: • MI-DenseCFNet combines deep learning neural networks with crucial clinical features to discern between Staphylococcus aureus pneumonia and Aspergillus pneumonia. • The comprehensive group had an area under the curve of 0.92, surpassing the proficiency of junior radiologists. • This model can enhance a primary radiologist's diagnostic capacity.

Soluble Gd6Cu24 clusters: effective molecular electrocatalysts for water oxidation.

The water oxidation half reaction in water splitting for hydrogen production is extremely rate-limiting. This study reports the synthesis of two heterometallic clusters (Gd6Cu24-IM and Gd6Cu24-AC) for application as efficient water oxidation catalysts. Interestingly, the maximum turnover frequency of Gd6Cu24-IM in an NaAc solution of a weak acid (pH 6) was 319 s-1. The trimetallic catalytic site, H2O-GdIIICuII2-H2O, underwent two consecutive two-electron two-proton coupled transfer processes to form high-valent GdIII-O-O-CuIII2 intermediates. Furthermore, the O-O bond was formed via intramolecular interactions between the CuIII and GdIII centers. The results of this study revealed that synergistic catalytic water oxidation between polymetallic sites can be an effective strategy for regulating O-O bond formation.

Analysis of the differentially expressed genes in the combs and testes of Qingyuan partridge roosters at different developmental stages.

BACKGROUND: The sexual maturity of chickens is an important economic trait, and the breeding of precocious and delayed puberty roosters is an important selection strategy for broilers. The comb serves as an important secondary sexual characteristic of roosters and determines their sexual precocity. Moreover, comb development is closely associated with gonad development in roosters. However, the underlying molecular mechanism regulating the sexual maturity of roosters has not yet been fully explored. RESULTS: In order to identify the genes related to precocious puberty in Qingyuan partridge roosters, and based on the synchrony of testis and combs development, combined with histological observation and RNA-seq method, the developmental status and gene expression profile of combs and testis were obtained. The results showed that during the early growth and development period (77 days of age), the development of combs and testis was significant in the high comb (H) group versus the low comb (L) group (p < 0.05); however, the morphological characteristic of the comb and testicular tissues converged during the late growth and development period (112 days of age) in the H and L groups. Based on these results, RNA-sequencing analysis was performed on the comb and testis tissues of the 77 and 112 days old Qingyuan Partridge roosters with different comb height traits. GO and KEGG analysis enrichment analysis showed that the differentially expressed genes were primarily enriched in MAPK signaling, VEGF signaling, and retinol metabolism pathways. Moreover, weighted correlation network analysis and module co-expression network analysis identified WNT6, AMH, IHH, STT3A, PEX16, KPNA7, CATHL2, ROR2, PAMR1, WISP2, IL17REL, NDRG4, CYP26B1, and CRHBP as the key genes associated with the regulation of precocity and delayed puberty in Qingyuan Partridge roosters. CONCLUSIONS: In summary, we identified the key regulatory genes of sexual precocity in roosters, which provide a theoretical basis for understanding the developmental differences between precocious and delayed puberty in roosters.

2,6-diaminopurine (Z)-containing toehold probes improve genotyping sensitivity.

2,6-diaminopurine (Z), a naturally occurring noncanonical nucleotide base found in bacteriophages, enhances DNA hybridization by forming three hydrogen bonds with thymine (T). These distinct biochemical characteristics make it particularly valuable in applications that rely on the thermodynamics of DNA hybridization. However, the practical use of Z-containing oligos is limited by their high production cost and the challenges associated with their synthesis. Here, we developed an efficient and cost-effective approach to synthesize Z-containing oligos of high quality based on an isothermal strand displacement reaction. These newly synthesized Z-oligos are then employed as toehold-blockers in an isothermal genotyping assay designed to detect rare single nucleotide variations (SNV). When compared with their counterparts containing the standard adenine (A) base, the Z-containing blockers significantly enhance the accuracy of identifying SNV. Overall, our innovative methodology in the synthesis of Z-containing oligos, which can also be used to incorporate other unconventional and unnatural bases into oligonucleotides, is anticipated to be adopted for diverse applications, including genotyping, biosensing, and gene therapy.

Selective 1,2-Hydroarylation(Alkenylation) of gem-Difluoroalkenes to Access (-CF2 H) Motifs.

An emerging class of C-C coupling transformations that furnish drug-like building blocks involves catalytic hydrocarbonation of alkenes. However, despite notable advances in the field, hydrocarbon addition to gem-difluoroalkenes without additional electronic activation remains largely unsuccessful. This owes partly to poor reactivity and the propensity of difluoroalkenes to undergo defluorinative side reactions. Here, we report a nickel catalytic system that promotes efficient 1,2-selective hydroarylation and hydroalkenylation, suppressing defluorination and providing straightforward access to a diverse assortment of prized organofluorides bearing difluoromethyl-substituted carbon centers. In contrast to radical-based pathways and reactions triggered by hydrometallation via a nickel-hydride complex, our experimental and computational studies support a mechanism in which a catalytically active nickel-bromide species promotes selective carbonickelation with difluoroalkenes followed by alkoxide exchange and hydride transfer, effectively overcoming the difluoroalkene's intrinsic electronic bias.

Vascular endothelial growth factor B improves impaired glucose tolerance through insulin-mediated inhibition of glucagon secretion.

BACKGROUND: Impaired glucose tolerance (IGT) is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes. When IGT occurs, insulin sensitivity decreases, causing a reduction in insulin secretion and an increase in glucagon secretion. Recently, vascular endothelial growth factor B (VEGFB) has been demonstrated to play a positive role in improving glucose metabolism and insulin sensitivity. Therefore, we constructed a mouse model of IGT through high-fat diet feeding and speculated that VEGFB can regulate hyperglycemia in IGT by influencing insulin-mediated glucagon secretion, thus contributing to the prevention and cure of prediabetes. AIM: To explore the potential molecular mechanism and regulatory effects of VEGFB on insulin-mediated glucagon in mice with IGT. METHODS: We conducted in vivo experiments through systematic VEGFB knockout and pancreatic-specific VEGFB overexpression. Insulin and glucagon secretions were detected via enzyme-linked immunosorbent assay, and the protein expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) was determined using western blot. Further, mRNA expression of forkhead box protein O1, phosphoenolpyruvate carboxykinase, and glucose-6 phosphatase was detected via quantitative polymerase chain reaction, and the correlation between the expression of proteins was analyzed via bioinformatics. RESULTS: In mice with IGT and VEGFB knockout, glucagon secretion increased, and the protein expression of PI3K/AKT decreased dramatically. Further, in mice with VEGFB overexpression, glucagon levels declined, with the activation of the PI3K/AKT signaling pathway. CONCLUSION: VEGFB/vascular endothelial growth factor receptor 1 can promote insulin-mediated glucagon secretion by activating the PI3K/AKT signaling pathway to regulate glucose metabolism disorders in mice with IGT.

Effect of N2 and CO2 on the Explosion Properties of High Equivalence Ratios of Hydrogen.

The explosion characteristics of premixed gases under different equivalence ratios (1.0-3.0) and inert gas addition (5-20%) are experimentally investigated, and sensitivity analysis of the radical reactions is carried out using the USC Mech II model to analyze the molar fraction of radicals. The results show that at high equivalence ratios, inert gas has little effect on flame stability. The addition of an inert gas reduces the tensile rate in the early stage of flame growth. At high equivalence ratios, CO2 inhibits explosive flame propagation twice as effectively as N2. Due to the large heat capacity and chemical kinetic effects, CO2 has a stronger inhibitory effect on the explosion pressure than N2, and the inhibition efficiency on the explosion strength is nearly twice that high. To further analyze the effect of different inert gas addition ratios on chemical kinetics, sensitivity analysis, and molar fraction simulations were performed. The thermal and chemical kinetic effects of CO2 cause later generation of H and OH radicals and the partial chain reaction involving CO2 causes a lower peak of H radicals than the peak of H radicals generated under an N2 atmosphere. However, CO2 is a direct reactant and the third body to produce a small chemical kinetic effect.

A 'one stone, two birds' approach with mesenchymal stem cells for acute respiratory distress syndrome and Type II diabetes mellitus.

This review explores the intricate relationship between acute respiratory distress syndrome (ARDS) and Type II diabetes mellitus (T2DM). It covers ARDS epidemiology, etiology and pathophysiology, along with current treatment trends and challenges. The lipopolysaccharides (LPS) role in ARDS and its association between non-communicable diseases and COVID-19 are discussed. The review highlights the therapeutic potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) for ARDS and T2DM, emphasizing their immunomodulatory effects. This review also underlines how T2DM exacerbates ARDS pathophysiology and discusses the potential of hUC-MSCs in modulating immune responses. In conclusion, the review highlights the multidisciplinary approach to managing ARDS and T2DM, focusing on inflammation, oxidative stress and potential therapy of hUC-MSCs in the future.

Recent Advances in First-Row Transition Metal-Catalyzed Reductive Coupling Reactions for π-Bond Functionalization and C-Glycosylation.

ConspectusEfficient construction of ubiquitous carbon-carbon bonds between two electrophiles has garnered interest in recent decades, particularly if it is mediated by nonprecious, first-row transition metals. Reductive coupling has advantages over traditional cross-coupling by obviating the need for stoichiometric air- and moisture-sensitive organometallic reagents. By harnessing transition metal-catalyzed reductive coupling as a powerful tool, intricate molecular architectures can be readily assembled through the installation of two C-C bonds across π systems (alkenes/alkynes) via reaction with two appropriate electrophiles. Despite advances in reductive alkene difunctionalization, there remains significant potential for the discovery of novel reaction pathways. In this regard, development of reductive protocols that enable the union of challenging alkyl/alkynyl electrophiles in high regio- and chemoselectivity remains a highly sought-after goal.Apart from π-bond functionalization, reductive coupling has found application in carbohydrate chemistry, particularly in the synthesis of valuable C-glycosyl compounds. In this vein, suitable glycosyl donors can be used to generate reactive glycosyl radical intermediates under reductive conditions. Through elaborately designed reactions, these intermediates can be trapped to furnish pharmaceutically relevant glycoconjugates. Consequently, diversification in C-glycosyl compound synthesis using first-row transition metal catalysis holds strong appeal.In this Account, we summarize our efforts in the development of first-row transition metal-catalyzed reductive coupling reactions for applications in alkene/alkyne functionalization and C-glycosylation. We will first discuss the nickel (Ni)-catalyzed reductive difunctionalization of alkenes, aided by an 8-aminoquinoline (AQ) directing auxiliary. Next, we highlight the Ni-catalyzed hydroalkylation of alkenyl amides tethered with a similar AQ-derived directing auxiliary. Lastly, we discuss an efficient synthesis of 1,3-enynes involving site- and stereoselective reductive coupling of terminal alkynes with alkynyl halides and NHPI esters.Beyond alkene dicarbofunctionalization, we extended the paradigm of transition metal-catalyzed reductive coupling toward the construction of C-glycosidic linkages in carbohydrates. By employing an earth-abundant iron (Fe)-based catalyst, we show that useful glycosyl radicals can be generated from glycosyl chlorides under reductive conditions. These intermediates can be captured in C-C bond formation to furnish valuable C-aryl, C-alkenyl, and C-alkynyl glycosyl compounds with high diastereoselectivity. Our Ni-catalyzed multicomponent union of glycosyl chlorides, aryl/alkyl iodides, and isobutyl chloroformate under reductive conditions led to the stereoselective synthesis of C-acyl glycosides. In addition to Fe and Ni, we discovered a Ti-catalyzed/Mn-promoted synthetic route to access C-alkyl and C-alkenyl glycosyl compounds, through the reaction of glycosyl chlorides with electron-deficient alkenes/alkynes. We further developed an electron donor-acceptor (EDA) photoactivation system leveraging decarboxylative and deaminative strategies for C-glycosylation under Ni catalysis. This approach has been demonstrated to selectively activate carboxyl and amino motifs to furnish glycopeptide conjugates. Finally, through two distinct catalytic transformations of bench-stable heteroaryl glycosyl sulfones, we achieved stereodivergent access to both α- and ß-anomers of C-aryl glycosides, one of which involves a Ni-catalyzed reductive coupling with aryl iodides.The findings presented in this Account are anticipated to have far-reaching implications beyond our research. We foresee that these results will pave the way for new transformations founded on the concept of reductive coupling, leading to the discovery of novel applications in the future.