Uncovering ghost introgression through genomic analysis of a distinct eastern Asian hickory species.

Ghost introgression, or the transfer of genetic material from extinct or unsampled lineages to sampled species, has attracted much attention. However, conclusive evidence for ghost introgression, especially in plant species, remains scarce. Here, we newly assembled chromosome-level genomes for both Carya sinensis and Carya cathayensis, and additionally re-sequenced the whole genomes of 43 C. sinensis individuals as well as 11 individuals representing 11 diploid hickory species. These genomic datasets were used to investigate the reticulation and bifurcation patterns within the genus Carya (Juglandaceae), with a particular focus on the beaked hickory C. sinensis. By combining the D-statistic and BPP methods, we obtained compelling evidence that supports the occurrence of ghost introgression in C. sinensis from an extinct ancestral hickory lineage. This conclusion was reinforced through the phylogenetic network analysis and a genome scan method VolcanoFinder, the latter of which can detect signatures of adaptive introgression from unknown donors. Our results not only dispel certain misconceptions about the phylogenetic history of C. sinensis but also further refine our understanding of Carya's biogeography via divergence estimates. Moreover, the successful integration of the D-statistic and BPP methods demonstrates their efficacy in facilitating a more precise identification of introgression types.

Neoadjuvant camrelizumab plus apatinib for locally advanced microsatellite instability-high or mismatch repair-deficient colorectal cancer (NEOCAP): a single-arm, open-label, phase 2 study.

BACKGROUND: PD-1 blockade is highly efficacious for mismatch repair-deficient colorectal cancer in both metastatic and neoadjuvant settings. We aimed to explore the activity and safety of neoadjuvant therapy with PD-1 blockade plus an angiogenesis inhibitor and the feasibility of organ preservation in patients with locally advanced mismatch repair-deficient colorectal cancer. METHODS: We initiated a single-arm, open-label, phase 2 trial (NEOCAP) at Sun Yat-sen University Cancer Center and the Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China. Patients aged 18-75 years with untreated mismatch repair-deficient or microsatellite instability-high or POLE/POLD1-mutated locally advanced colorectal cancer (cT3 or N+ for rectal cancer, and T3 with invasion ≥5mm or T4, with or without N+ for colon cancer) and an Eastern Cooperative Oncology Group performance score of 0-1 were enrolled and given 200 mg camrelizumab intravenously on day 1 and 250 mg apatinib orally from day 1-14, every 3 weeks for 3 months followed by surgery or 6 months if patients did not have surgery. Patients who had a clinical complete response did not undergo surgery and proceeded with a watch-and-wait approach. The primary endpoint was the proportion of patients with a pathological or clinical complete response. Eligible enrolled patients who received at least one cycle of neoadjuvant treatment and had at least one tumour response assessment following the baseline assessment were included in the activity analysis, and patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04715633) and is ongoing. FINDINGS: Between Sept 29, 2020, and Dec 15, 2022, 53 patients were enrolled; one patient was excluded from the activity analysis because they were found to be mismatch repair-proficient and microsatellite-stable. 23 (44%) patients were female and 29 (56%) were male. The median follow-up was 16·4 (IQR 10·5-23·5) months. 28 (54%; 95% CI 35-68) patients had a clinical complete response and 24 of these patients were managed with a watch-and-wait approach, including 20 patients with colon cancer and multiple primary colorectal cancer. 23 (44%) of 52 patients underwent surgery for the primary tumour, and 14 (61%; 95% CI 39-80) had a pathological complete response. 38 (73%; 95% CI 59-84) of 52 patients had a complete response. Grade 3-5 adverse events occurred in 20 (38%) of 53 patients; the most common were increased aminotransferase (six [11%]), bowel obstruction (four [8%]), and hypertension (four [8%]). Drug-related serious adverse events occurred in six (11%) of 53 patients. One patient died from treatment-related immune-related hepatitis. INTERPRETATION: Neoadjuvant camrelizumab plus apatinib show promising antitumour activity in patients with locally advanced mismatch repair-deficient or microsatellite instability-high colorectal cancer. Immune-related adverse events should be monitored with the utmost vigilance. Organ preservation seems promising not only in patients with rectal cancer, but also in those with colon cancer who have a clinical complete response. Longer follow-up is needed to assess the oncological outcomes of the watch-and-wait approach. FUNDING: The National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, and the Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Genomic Insights into Adaptation to Karst Limestone and Incipient Speciation in East Asian Platycarya spp. (Juglandaceae).

When challenged by similar environmental conditions, phylogenetically distant taxa often independently evolve similar traits (convergent evolution). Meanwhile, adaptation to extreme habitats might lead to divergence between taxa that are otherwise closely related. These processes have long existed in the conceptual sphere, yet molecular evidence, especially for woody perennials, is scarce. The karst endemic Platycarya longipes, and its only congeneric species, P. strobilacea, which is widely distributed in the mountains in East Asia, provide an ideal model for examining the molecular basis of both convergent evolution and speciation. Using chromosome-level genome assemblies of both species, and whole genome resequencing data from 207 individuals spanning their entire distribution range, we demonstrate that P. longipes and P. strobilacea form two species-specific clades, which diverged around 2.09 million years ago. We find an excess of genomic regions exhibiting extreme interspecific differentiation, potentially due to long-term selection in P. longipes, likely contributing to the incipient speciation of the genus Platycarya. Interestingly, our results unveil underlying karst adaptation in both copies of the calcium influx channel gene TPC1 in P. longipes. TPC1 has previously been identified as a selective target in certain karst-endemic herbs, indicating a convergent adaptation to high calcium stress among karst-endemic species. Our study reveals the genic convergence of TPC1 among karst endemics, and the driving forces underneath the incipient speciation of the two Platycarya lineages.

Genomic Insights into Adaptation to Karst Limestone and Incipient Speciation in East Asian Platycarya spp. (Juglandaceae).

When challenged by similar environmental conditions, phylogenetically distant taxa often independently evolve similar traits (convergent evolution). Meanwhile, adaptation to extreme habitats might lead to divergence between taxa that are otherwise closely related. These processes have long existed in the conceptual sphere, yet molecular evidence, especially for woody perennials, is scarce. The karst endemic Platycarya longipes and its only congeneric species, Platycarya strobilacea, which is widely distributed in the mountains in East Asia, provide an ideal model for examining the molecular basis of both convergent evolution and speciation. Using chromosome-level genome assemblies of both species, and whole-genome resequencing data from 207 individuals spanning their entire distribution range, we demonstrate that P. longipes and P. strobilacea form two species-specific clades, which diverged around 2.09 million years ago. We find an excess of genomic regions exhibiting extreme interspecific differentiation, potentially due to long-term selection in P. longipes, likely contributing to the incipient speciation of the genus Platycarya. Interestingly, our results unveil underlying karst adaptation in both copies of the calcium influx channel gene TPC1 in P. longipes. TPC1 has previously been identified as a selective target in certain karst-endemic herbs, indicating a convergent adaptation to high calcium stress among karst-endemic species. Our study reveals the genic convergence of TPC1 among karst endemics and the driving forces underneath the incipient speciation of the two Platycarya lineages.

Development of an Ultrasensitive Competitive Double-Enzyme Cascade Fluorescence Signal Amplification Method for Factor XIa Inhibitor Screening.

Coagulation factor XIa (FXIa) is associated with a low risk of bleeding and has been identified as an effective and safe target for the development of novel anticoagulant drugs. In this study, we established an ultrasensitive competitive dual-enzyme cascade signal amplification method for the quantitative analysis and screening of FXIa inhibitors. Due to the specific recognition of FXIa's active site by the aptamer AptE40, the AptE40-QDs-EK recognition probe modified with enterokinase (EK) and the aptamer AptE40, was attached to the MNPs-FXIa capture probe. When FXIa inhibitor was present, it competed with AptE40 for binding to FXIa, resulting in the detachment of AptE40-QDs-EK from MNPs-FXIa. After magnetic separation, the enterokinase of AptE40-QDs-EK in the supernatant hydrolyzed N-terminal hexapeptide of trypsinogen, leading to the production of a large amount of trypsin as part of the first-stage signal cascade amplification. Next, trypsin could hydrolyze the hexameric arginine peptide (RRRRRR, R6), leading to the dissociation of RQDs from the R6-RQDs signal probe; this resulted in a dramatic increase in the fluorescence intensity of the supernatant as the second-stage signal cascade was amplified. The feasibility of the method was investigated using the FXIa inhibitor aptamer FELIAP as a positive model drug. Furthermore, the method was applied to screen the FXIa inhibitors in Eupolyphaga sinensis Walker. Two fractions with more active anticoagulated ingredients were successfully identified and validated via the conventional method, and the results were consistent. The established method provides a key technique for the sensitive detection, high-throughput analysis, and screening of the FXIa inhibitors.

Co-augmentation of a transport gene mfsT1 in Mycolicibacterium neoaurum with genome engineering to enhance ergothioneine production.

Ergothioneine (EGT) is a rare thiohistidine derivative with exceptional antioxidant properties. The blood level of EGT is considered highly reliable predictors for cardiovascular diseases and mortality, yet animals lack the ability to synthesize this compound. Free plasmids have been previously used to overexpress genes involved in the EGT biosynthetic pathway of Mycolicibacterium neoaurum. Here, we tentatively introduced a putative transporter gene mfsT1 into high-copy plasmids and sharply increased the ratio of extracellular EGT concentration from 18.7% to 44.9%. Subsequently, an additional copy of egtABCDE, hisG, and mfsT1 was inserted into the genome with a site-specific genomic integration tool of M. neoaurum, leading a 2.7 times increase in EGT production. Co-enhancing the S-adenosyl-L-methionine regeneration pathway, or alternatively, the integration of three copies of egtABCDE, hisG and mfsT1 into the genome further increased the total EGT yield by 16.1% (64.6 mg/L) and 21.7% (67.7 mg/L), respectively. After 168-h cultivation, the highest titer reached 85.9 mg/L in the latter strain with three inserted copies. This study provided a solid foundation for genome engineering to increase the production of EGT in M. neoaurum.

A High-Efficiency Bioorthogonal Tumor-Membrane Reactor for In Situ Selective and Sustained Prodrug Activation.

The site-specific activation of bioorthogonal prodrugs has provided great opportunities for reducing the severe side effects of chemotherapy. However, the precise control of activation location, sustained drug production at the target site, and high bioorthogonal reaction efficiency in vivo remain great challenges. Here, we propose the construction of tumor cell membrane reactors in vivo to solve the above problems. Specifically, tumor-targeted liposomes with efficient membrane fusion capabilities are generated to install the bioorthogonal trigger, the amphiphilic tetrazine derivative, on the surface of tumor cells. These predecorated tumor cells act as many living reactors, transforming the tumor into a "drug factory" that in situ activates an externally delivered bioorthogonal prodrug, for example intratumorally injected transcyclooctene-caged doxorubicin. In contrast to the rapid elimination of cargo that is encapsulated and delivered by liposomes, these reactors permit stable retention of bioorthogonal triggers in tumor for 96 h after a single dose of liposomes via intravenous injection, allowing sustained generation of doxorubicin. Interestingly, an additional supplement of liposomes will compensate for the trigger consumed by the reaction and significantly improve the efficiency of the local reaction. This strategy provides a solution to the efficacy versus safety dilemma of tumor chemotherapy.

[Efficacy of therapeutic hypothermia on mild neonatal hypoxic-ischemic encephalopathy: a prospective randomized controlled study]. / æ–°ç”Ÿå„¿è½»åº¦ç¼ºæ°§ç¼ºè¡€æ€§è„‘ç— äºšä½Žæ¸©æ²»ç–—æ•ˆæžœçš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To investigate the efficacy of therapeutic hypothermia on mild neonatal hypoxic-ischemic encephalopathy (HIE). METHODS: A prospective study was performed on 153 neonates with mild HIE who were born from September 2019 to September 2023. These neonates were randomly divided into two groups: therapeutic hypothermia (n=77) and non-therapeutic hypothermia group (n=76). The short-term clinical efficacy of the two groups were compared. Barkovich scoring system was used to analyze the severity of brain injury shown on magnetic resonance imaging (MRI) between the two groups. RESULTS: There were no significant differences in gestational age, gender, birth weight, mode of birth, and Apgar score between the therapeutic hypothermia and non-therapeutic hypothermia groups (P>0.05). There were no significant differences in the incidence rates of sepsis, arrhythmia, persistent pulmonary hypertension and pulmonary hemorrhage and the duration of mechanical ventilation within the first 72 hours after birth between the two groups. The therapeutic hypothermia group had longer prothrombin time within the first 72 hours after birth and a longer hospital stay (P<0.05). Compared with the non-therapeutic hypothermia group, the therapeutic hypothermia group had lower incidence rates of MRI abnormalities (30% vs 57%), moderate to severe brain injury on MRI (5% vs 28%), and watershed injury (27% vs 51%) (P<0.05), as well as lower medium watershed injury score (0 vs 1) (P<0.05). CONCLUSIONS: Therapeutic hypothermia can reduce the incidence rates of MRI abnormalities and watershed injury, without obvious adverse effects, in neonates with mild HIE, suggesting that therapeutic hypothermia may be beneficial in neuroprotection in these neonates.

Dead-End Hybridization in Walnut Trees Revealed by Large-Scale Genomic Sequence Data.

Although hybridization plays a large role in speciation, some unknown fraction of hybrid individuals never reproduces, instead remaining as genetic dead-ends. We investigated a morphologically distinct and culturally important Chinese walnut, Juglans hopeiensis, suspected to have arisen from hybridization of Persian walnut (J. regia) with Asian butternuts (J. cathayensis, J. mandshurica, and hybrids between J. cathayensis and J. mandshurica). Based on 151 whole-genome sequences of the relevant taxa, we discovered that all J. hopeiensis individuals are first-generation hybrids, with the time for the onset of gene flow estimated as 370,000 years, implying both strong postzygotic barriers and the presence of J. regia in China by that time. Six inversion regions enriched for genes associated with pollen germination and pollen tube growth may be involved in the postzygotic barriers that prevent sexual reproduction in the hybrids. Despite its long-recurrent origination and distinct traits, J. hopeiensis does not appear on the way to speciation.

Virus-like Iron-Gold Heterogeneous Nanoparticles for Drug Target Screening.

Drug-target recognition has great impacts on revealing mechanisms of pharmacological activities, especially drug resistance and off-target effects. In recent years, chemoproteomics has been widely used for drug target screening and discovery due to its high-throughput, high accuracy, and sensitivity. However, there still remain challenges on how to efficiently and unambiguously track target proteins from complex biological matrices. Herein, we report a drug target screening method based on virus-like iron-gold heterogeneous nanoparticles (Au@Fe3O4 NPs). The unique structure of Au@Fe3O4 NPs not only maintains the magnetism of Fe3O4 NPs to facilitate protein enrichment and purification, but also increases drug modification by introducing more active sites on the surface of Au NPs. After coincubating the drug modified NPs with the cell lysate, the high loading of drug on the surface of Au@Fe3O4 NPs was beneficial for capturing target proteins with low abundance. This well-designed heterogeneous nanomaterial provides a novel strategy for improving the efficiency and accuracy of affinity-based proteomics.

Multimorbidity patterns and the association with health status of the oldest-old in long-term care facilities in China: a two-step analysis.

BACKGROUND: The increasing prevalence of multimorbidity has created a serious global public health problem in aging populations. Certain multimorbidity patterns across different age ranges and their association with health status remain unclear. The main aim of this study is to identify multimorbidity patterns discrepancies and associated health status between younger-old and oldest-old. METHODS: The Ethics Committee of Nanjing Medical University approved the study protocol (No.2019-473). Convenience sampling method was used to recruit older adults aged ≥ 60 years with multimorbidity from July to December 2021 from 38 Landsea long-term care facilities in China. The multimorbidity patterns were analyzed using network analysis and two-step cluster analysis. One-Way ANOVA was utilized to explore their association with health status including body function, activity of daily living, and social participation. A Sankey diagram visualized the flow of health status within different multimorbidity patterns. This study is reported following the STROBE guidelines. RESULTS: A total of 214 younger-old (60-84 years) and 173 oldest-old (≥ 85 years) were included. Leading coexisting diseases were cardiovascular disease (CD), metabolic and endocrine disease (MED), neurological disease (ND), and orthopedic disease (OD). Cluster 1 (53, 24.8%) of CD-ND (50, 94.3%; 31, 58.8%), cluster 2 (39, 18.2%) of MED-ND-CD (39, 100%; 39, 100%; 37, 94.9%), cluster 3 (37, 17.3%) of OD-CD-MED-ND (37, 100%; 33, 89.2%; 27, 73.0%; 16, 43.2%), and cluster 4 (34, 15.9%) of CD-MED (34, 100%; 34, 100%) were identified in the younger-old. In the oldest-old, the primary multimorbidity patterns were: cluster 1 (33, 19.1%) of CD-respiratory disease-digestive disease-urogenital disease (CD-RD-DSD-UD) (32, 97.0%; 9, 27.3%; 8, 24.2%; 7, 21.2%), cluster 2 (42, 24.3%) of ND-CD-MED (42, 100%; 35, 83.3%; 14, 33.3%), cluster 3 (28, 16.2%) of OD-CD-MED (28, 100%; 25, 89.3%; 18, 64.3%), and cluster 4 (35, 20.2%) of CD-MED (35, 100%; 35, 100%). Younger-old with CD-ND or MED-ND-CD, and oldest-old with ND-CD-MED have worse health status compared with other multimorbidity patterns (e.g., CD-MED and OD-CD-MED). CONCLUSION: Discrepancies in common patterns of multimorbidity across age groups suggest that caregivers in long-term care facilities should consider changes in multimorbidity patterns with ageing when developing prevention plans for individualized management. Neurological disease concurrent with other diseases was the major determinant of health status, especially for the oldest-old. Interventions targeting multimorbidity need to be focused, yet generic. It is essential to assess complex needs and health outcomes that arise from different multimorbidity patterns and manage them through an interdisciplinary approach and consider their priorities to gain high-quality primary care for older adults living in long-term care facilities.

Operative strategies for ankylosing spondylitis-related thoracolumbar kyphosis: focus on the cervical stiffness, coronal imbalance and hip involvement.

BACKGROUND: Cervical stiffness, coronal imbalance and limited hip movement all play crucial roles in designing the corrective surgery for ankylosing spondylitis-related thoracolumbar kyphosis (AS-TLK). However, a comprehensive classification and tailored strategies for directing clinical work are lacking. This study aims to investigate the types and surgical strategies for AS-TLK that consider cervical stiffness, coronal imbalance and hip involvement as the key factors. METHODS: 25 consecutive AS-TLK patients were divided into three types according to their accompanying features: Type I: with a flexible cervical spine; Type IIA: with a stiff cervical spine; Type IIB: with coronal imbalance; Type IIC: with limited hip movement. Type III is the mixed type with at least two conditions of Type II. Individual strategies were given correspondingly. Spinal-pelvic-femoral parameters were measured, Scoliosis Research Society outcome instrument-22 (SRS-22) was used and complications were recorded and analysed. RESULTS: All patients (Type I 10, Type II 8 and Type III 7) underwent surgery successfully. 13 cases with 16 complications were recorded and cured. The patients were followed up for 24-65 months with an average of 33.0 ± 9.6 months. Both the sagittal and coronal parameters were corrected and decreased significantly (all, p < 0.05). SRS-22 scores showed a satisfactory outcome. CONCLUSION: Thoracolumbar kyphosis secondary to ankylosing spondylitis are complex and variable. Considering the factors of cervical stiffness, coronal imbalance and hip involvement assists in making decisions individually and achieving a desired surgical result.

Cinepazide maleate promotes recovery from spinal cord injury by inhibiting inflammation and prolonging neuronal survival.

This study aimed to investigate the therapeutic effects of cinepazide maleate (CM) on spinal cord injury (SCI) in rats, thereby providing an experimental basis for the use of CM as a preventative and therapeutic strategy for SCI. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining and western blot analysis were used to assess neural cell apoptosis. enzyme-linked immunosorbent assay was used to analyze the expression of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) in spinal cord tissues and cerebrospinal fluid. CD68 staining and western blot analysis were used to investigate the effect of CM on microglia activation. The effects of CM on motor function and histological damage in rats after SCI were investigated using the Basso-Beattie-Bresnahan (BBB) score, footprint assay, hematoxylin and eosin staining, and NeuN staining. In vitro models of neuronal cell injury and microglial inflammation were developed to investigate the effects of CM on apoptosis and inflammation. Functional tests (BBB score and footprint test) revealed that CM-treated rats had significantly improved motor function. In vivo CM treatment reduced the number of apoptotic cells at the site of injury. Similarly, in vitro CM treatment reduced H2 O2 -induced neuronal apoptosis. In vivo CM treatment reduced the number of CD68-positive microglia and the expression levels of TNF-α, IL-1ß, and IL-6. Similarly, in vitro CM treatment reduced LPS-induced pro-inflammatory cytokines in microglia. CM promotes the recovery of motor function by inhibiting SCI-induced apoptosis and inflammatory responses and reducing the area of the post-SCI cavity in rats. These findings indicate that CM is a potential drug worthy of translational studies for SCI treatment.

Core-Shell Reactor Partitioning Enzyme and Prodrug by ZIF-8 for NADPH-Sensitive In Situ Prodrug Activation.

Enzyme-prodrug therapies have shown unique advantages in efficiency, selectivity, and specificity of in vivo prodrug activation. However, precise spatiotemporal control of both the enzyme and its substrate at the target site, preservation of enzyme activity, and in situ substrate depletion due to low prodrug delivery efficiency continue to be great challenges. Here, we propose a novel core-shell reactor partitioning enzyme and prodrug by ZIF-8, which integrates an enzyme with its substrate and increases the drug loading capacity (DLC) using a prodrug as the building ligand to form a Zn-prodrug shell. Cytochrome P450 (CYP450) is immobilized in ZIF-8, and the antitumor drug dacarbazine (DTIC) is coordinated and deposited in its outer layer with a high DLC of 43.6±0.8 %. With this configuration, a much higher prodrug conversion efficiency of CYP450 (36.5±1.5 %) and lower IC50 value (26.3±2.6 µg/mL) are measured for B16-F10 cells with a higher NADPH concentration than those of L02 cells and HUVECs. With the tumor targeting ability of hyaluronic acid, this core-shell enzyme reactor shows a high tumor suppression rate of 96.6±1.9 % and provides a simple and versatile strategy for enabling in vivo biocatalysis to be more efficient, selective, and safer.

Aryl-to-Vinyl 1,4-Nickel Migration/Reductive Cross-Coupling Reaction for the Stereoselective Synthesis of Multisubstituted Olefins.

The aryl-to-vinyl nickel 1,4-migration (1,4-Ni migration) reaction has been reported for the first time. The generated alkenyl Ni species undergo a reductive coupling reaction with unactivated brominated alkanes affording a series of trisubstituted olefins. This tandem reaction exhibits mild conditions, a broad substrate scope, high regioselectivity, and excellent Z/E stereoselectivity. A series of controlled experiments have shown that the critical 1,4-Ni migration process is reversible. In addition, the alkenyl nickel intermediates obtained after migration are highly Z/E stereoselective and do not undergo Z/E isomerization. The obtained trace isomerization products are caused by the instability of the product.

New Bioactive Polyacetylenes from the Marine Sponge Petrosia sp.

Three new polyacetylenes, pellynols P (1), Q (2), and R (3) were isolated from the marine sponge Petrosia sp., along with the known compound pellynol H (4). Their structures were determined by analyses of extensive NMR, HR-MS, and ESI-MS/MS data. All compounds displayed potent cytotoxicities against human hepatocellular carcinoma HepG2, human melanoma A375, and human colorectal carcinoma HT29 cell lines with IC50 values at the range of 1.4-4.4 µM.

[Overview of Meta-analysis of Lianhua Qingwen preparations in treatment of viral diseases].

This study aims to obtain higher-level evidence by overviewing the Meta-analysis of Lianhua Qingwen preparations in the treatment of viral diseases including influenza, coronavirus disease 2019(COVID-19), and hand, foot and mouth disease(HFMD). CNKI, Wanfang, VIP, China Clinical Trial Registry(ChiCTR), PubMed, EMbase, Web of Science, and Cochrane Library were searched for the Meta-analysis about the treatment of viral diseases with Lianhua Qingwen preparations from the database establishment to April 1, 2022. After literature screening and data extraction, AMSTAR2 and the grading of recommendations assessment, development and evaluations(GRADE) system were used to assess the methodological quality and evidence quality, respectively, and then the efficacy and safety outcomes of Lianhua Qingwen preparations in the treatment of viral diseases were summarized. Thirteen Meta-analysis were finally included, three of which were rated as low grade by AMSTAR2 and ten as very low grade. A total of 75 outcome indicators were obtained, involving influenza, COVID-19, and HFMD. According to the GRADE scoring results, the 75 outcome indicators included 5(6.7%) high-level indicators, 18(24.0%) mediate-level indicators, 25(33.3%) low-level evidence indicators, and 27(36.0%) very low-level indicators.(1)In the treatment of influenza, Lianhua Qingwen preparations exhibited better clinical efficacy than other Chinese patent medicines and Ribavirin and had similar clinical efficacy compared with Oseltamivir. Lianhua Qingwen preparations were superior to other Chinese patent medicines, Oseltamivir, and Ribavirin in alleviating clinical symptoms. They showed no significant differences from Oseltamivir or conventional anti-influenza treatment in terms of the time to and rate of negative result of viral nucleic acid test.(2)In the treatment of COVID-19, Lianhua Qingwen preparation alone or combined with conventional treatment was superior to conventional treatment in terms of total effective rate, main symptom subsidence rate and time, fever clearance rate, duration of fever, time to fever clearance, cough subsidence rate, time to cough subsidence, fatigue subsidence rate, time to fatigue subsidence, myalgia subsidence rate, expectoration subsidence rate, chest tightness subsidence rate, etc. Lianhua Qingwen preparations no difference from conventional treatment in terms of subsiding sore throat, nausea, diarrhea, loss of appetite, headache, and dyspnea. In terms of chest CT improvement rate, rate of progression to severe case, cure time, and hospitalization time, Lianhua Qingwen alone or in combination with conventional treatment was superior to conventional treatment.(3)In the treatment of HFMD, Lianhua Qingwen Granules was superior to conventional treatment in terms of total effective rate, average fever clearance time, time to herpes subsidence, and time to negative result of viral nucleic acid test.(4)In terms of safety, Lianhua Qingwen preparations led to low incidence of adverse reactions, all of which were mild and disappeared after drug withdrawal. The available evidence suggests that in the treatment of influenza, COVID-19, and HFMD, Lianhua Qingwen preparations can relieve the clinical symptoms, shorten the hospitalization time, and improve the chest CT. They have therapeutic effect and good safety in the treatment of viral diseases. However, due to the low quality of available studies, more high-quality clinical trials are needed to support the above conclusions.

Ruthenium-Catalyzed Stereo- and Site-Selective ortho- and meta-C-H Glycosylation and Mechanistic Studies.

C-aryl glycosides are popular basic skeletons in biochemistry and pharmaceutical chemistry. Herein, ruthenium-catalyzed highly stereo- and site-selective ortho- and meta-CAr -H glycosylation is described. A series of C-aryl pyranosides and furanosides were synthesized by this method. The strategy showed good substrate scope, and various N-heterocyclic directing groups were compatible with the reaction system. A mechanistic study suggested that the key pathway of ortho-CAr -H glycosylation might involve oxidative addition/reduction elimination, whereas aryl meta-C-H glycosylation was mediated by σ-activation. Density functional theory calculations also showed that the high stereoselectivity of meta-CAr -H glycosylation was due to steric hindrance.

Insights into the Reactive and Deactivation Mechanisms of Manganese Oxides for Ozone Elimination: The Roles of Surface Oxygen Species.

Manganese oxides with varied Mn valance states but identical morphologies were synthesized via a facile thermal treatment of γ-MnOOH. Also, their catalytic performance on ozone decomposition was investigated following the order of Mn3O4 < Mn2O3 < MnO2 < MnO2-H-200. In combination with X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET), transmission electron microscopy (TEM), H2-temperature-programmed reduction (TPR), O2-temperature-programmed desorption (TPD), and X-ray photoelectron spectroscopy (XPS) characterization, it was deduced that the superior O3 decomposition capacity for MnO2-H-200 was strongly associated with abundant oxygen vacancies on its surface. Among Mn3O4, Mn2O3, and MnO2, the difference in O3 decomposition efficiency was dependent on the divergent nature of oxygen vacancy. Density functional theory (DFT) calculation revealed that Mn3O4 and MnO2 possessed lower formation energy of oxygen vacancy, while MnO2 had the minimum desorption energy of peroxide species (O2*). It was deduced that the promotion of the O3 decomposition capability was attributed to the easier O2* desorption. Insights into the deactivation mechanism for MnO2-H-200 further validated the assumptions. As the reaction proceeded, adsorbed oxygen species accumulated on the catalyst surface, and a portion of them were transformed to lattice oxygen. The consumption of oxygen vacancy led to the deactivation of the catalyst.

Adjuvant PD-1 inhibitor versus high-dose interferon α-2b for Chinese patients with cutaneous and acral melanoma: A retrospective cohort analysis.

The clinical efficacy of PD-1 inhibitors as an adjuvant treatment for Asian melanoma patients has not yet been determined. This retrospective study analyzed the clinical data of 90 Chinese patients with completely resected, stage III cutaneous or acral melanoma who received either adjuvant PD-1 inhibitor or high-dose interferon α-2b (HDI). Anti-PD-1 treatment resulted in significantly longer RFS and DMFS than HDI in cutaneous melanoma patients, with hazard ratios (HRs) (anti-PD-1 versus HDI) of 0.402 (95% CI, 0.183-0.886) and 0.324 (95%CI, 0.122 to 0.861) for RFS and DMFS, respectively. However, adjuvant anti-PD-1 treatment had no advantage over HDI in acral melanoma patients with HRs (anti-PD-1 versus HDI) of 1.204 (95% CI, 0.521 to 2.781) and 1.968(95% CI, 0.744-5.209) for RFS and DMFS, respectively. Adjuvant anti-PD-1 treatment yielded a significantly better prognosis than HDI in Chinese patients with stage IIIB/C cutaneous melanoma, but a significant difference was not observed in those with acral melanoma.