Scalable decarboxylative trifluoromethylation by ion-shielding heterogeneous photoelectrocatalysis.

Electrochemistry offers a sustainable synthesis route to value-added fine chemicals but is often constrained by competing electron transfer between the electrode and redox-sensitive functionalities distinct from the target site. Here, we describe an ion-shielding heterogeneous photoelectrocatalysis strategy to impose mass-transfer limitations that invert the thermodynamically determined order of electron transfer. This strategy is showcased to enable decarboxylative trifluoromethylation of sensitive (hetero)arenes by using trifluoroacetate, an inexpensive yet relatively inert trifluoromethyl group (CF3) source. An ion-shielding layer, formed by trifluoroacetate anions electrostatically adsorbed on a positive molybdenum-doped tungsten trioxide (WO3) photoanode, prevents undesired electron transfer between substrates and photogenerated holes. The practicality of the developed method was demonstrated with robust photoanode stability (approximately 380 hours), a good substrate scope, and scaling capability to achieve 100-gram synthesis by using photoelectrochemical flow cells.

A Graph-Neural-Network-Powered Solver Framework for Graph Optimization Problems.

Backtracking combined with branching heuristics is a prevalent approach for tackling constraint satisfaction problems (CSPs) and combinatorial optimization problems (COPs). While branching heuristics specifically designed for certain problems can be theoretically efficient, they are often complex and difficult to implement in practice. On the other hand, general branching heuristics can be applied across various problems, but at the risk of suboptimality. We introduce a solver framework that leverages the Shannon entropy in branching heuristics to bridge the gap between generality and specificity in branching heuristics. This enables backtracking to follow the path of least uncertainty, based on probability distributions that conform to problem constraints. We employ graph neural network (GNN) models with loss functions derived from the probabilistic method to learn these probability distributions. We have evaluated our approach by its applications to two NP-hard problems: the (minimum) dominating-clique problem and the edge-clique-cover problem. Compared with the state-of-the-art solvers for both problems, our solver framework outputs competitive results. Specifically, for the (minimum) dominating-clique problem, our approach generates fewer branches than the solver presented by Culberson et al. (2005). For the edge-clique-cover problem, our approach produces smaller-sized edge clique covers (ECCs) than the solvers referenced by Conte et al. (2020) and Kellerman (1973).

Advances in Mechanism of HIV-1 Immune Reconstitution Failure: Understanding Lymphocyte Subpopulations and Interventions for Immunological Nonresponders.

In individuals diagnosed with AIDS, the primary method of sustained suppression of HIV-1 replication is antiretroviral therapy, which systematically increases CD4+ T cell levels and restores immune function. However, there is still a subset of 10-40% of people living with HIV who not only fail to reach normal CD4+ T cell counts but also experience severe immune dysfunction. These individuals are referred to as immunological nonresponders (INRs). INRs have a higher susceptibility to opportunistic infections and non-AIDS-related illnesses, resulting in increased morbidity and mortality rates. Therefore, it is crucial to gain new insights into the primary mechanisms of immune reconstitution failure to enable early and effective treatment for individuals at risk. This review provides an overview of the dynamics of key lymphocyte subpopulations, the main molecular mechanisms of INRs, clinical diagnosis, and intervention strategies during immune reconstitution failure, primarily from a multiomics perspective.

Causative role of a novel intronic indel variant in FBN1 and maternal germinal mosaicism in Marfan syndrome.

BACKGROUND: Marfan syndrome (MFS) is an autosomal dominant connective tissue disease with wide clinical heterogeneity, and mainly caused by pathogenic variants in fibrillin-1 (FBN1). METHODS: A Chinese 4-generation MFS pedigree with 16 family members was recruited and exome sequencing (ES) was performed in the proband. Transcript analysis (patient RNA and minigene assays) and in silico structural analysis were used to determine the pathogenicity of the variant. In addition, germline mosaicism in family member (Ι:1) was assessed using quantitative fluorescent polymerase chain reaction (QF-PCR) and short tandem repeat PCR (STR) analyses. RESULTS: Two cis-compound benign intronic variants of FBN1 (c.3464-4 A > G and c.3464-5G > A) were identified in the proband by ES. As a compound variant, c.3464-5_3464-4delGAinsAG was found to be pathogenic and co-segregated with MFS. RNA studies indicated that aberrant transcripts were found only in patients and mutant-type clones. The variant c.3464-5_3464-4delGAinsAG caused erroneous integration of a 3 bp sequence into intron 28 and resulted in the insertion of one amino acid in the protein sequence (p.Ile1154_Asp1155insAla). Structural analyses suggested that p.Ile1154_Asp1155insAla affected the protein's secondary structure by interfering with one disulfide bond between Cys1140 and Cys1153 and causing the extension of an anti-parallel ß sheet in the calcium-binding epidermal growth factor-like (cbEGF)13 domain. In addition, the asymptomatic family member Ι:1 was deduced to be a gonadal mosaic as assessed by inconsistent results of sequencing and STR analysis. CONCLUSIONS: To our knowledge, FBN1 c.3464-5_3464-4delGAinsAG is the first identified pathogenic intronic indel variant affecting non-canonical splice sites in this gene. Our study reinforces the importance of assessing the pathogenic role of intronic variants at the mRNA level, with structural analysis, and the occurrence of mosaicism.

Influence of cachexia on immunotherapy efficacy and prognosis for malignant tumors of the digestive system.

BACKGROUND: The presence of cancer cachexia is a significant adverse prognostic indicator in patients with malignant tumors. Cancer cachexia is a multifactorial syndrome characterized by a constant loss of skeletal muscles with or without a loss of weight, leading to immune dysfunction. We performed a retrospective study to investigate the influence of cachexia on the immunotherapy efficacy and prognosis for malignant tumors of the digestive system. METHODS: The present study adopts a cross-sectional design. The prognosis data of patients with advanced cancer of the digestive system who received immunotherapy from September 2021 to December 2022 were analyzed. Cachexia was calculated using the change of the area of the psoas major muscle (PMMA) or the weight. We measured the change at the beginning of immunotherapy and at least 2 cycles afterward. The participants were categorized into the cachexia group and control group based on the evaluation criteria. Kaplan-Meier and Log-rank methods were used for survival analysis. Cox proportional hazard model as a method to assess the contribution of different clinical factors to overall survival (OS) and progression-free survival (PFS). RESULTS: A total number of 98 patients, including esophageal carcinoma (4, 4%), gastric (36, 37%), colorectal (51, 52%), and other cancer types (7, 7%), were enrolled. Fifty-four patients were diagnosed with non-cancer cachexia, and the cancer cachexia group included 44 patients. The median PFS in the cachexia group was shorter than that in the control group (130 days vs. 212 days). Their difference was not significant (p = .321). The survival rate of the patients without cachexia was longer than of those with cachexia (p = .027). The level of albumin and the number of metastatic organs were related to PFS (p = .020, p = .029). The albumin level was significantly associated with the OS of patients (p = .003). CONCLUSIONS: The presence of cachexia was significantly associated with poor OS in patients with malignant tumors of the digestive system who received immunotherapy, not with PFS or the response to immunotherapy.

Electron Manipulation and Surface Reconstruction of Bimetallic Iron-Nickel Phosphide Nanotubes for Enhanced Alkaline Water Electrolysis.

Developing high-efficiency and stable bifunctional electrocatalysts for water splitting remains a great challenge. Herein, NiMoO4 nanowires as sacrificial templates to synthesize Mo-doped NiFe Prussian blue analogs are employed, which can be easily phosphorized to Mo-doped Fe2xNi2(1-x)P nanotubes (Mo-FeNiP NTs). This synthesis method enables the controlled etching of NiMoO4 nanowires that results in a unique hollow nanotube architecture. As a bifunctional catalyst, the Mo-FeNiP NTs present lower overpotential and Tafel slope of 151.3 (232.6) mV at 100 mA cm-2 and 76.2 (64.7) mV dec-1 for HER (OER), respectively. Additionally, it only requires an ultralow cell voltage of 1.47 V to achieve 10 mA cm-2 for overall water splitting and can steadily operate for 200 h at 100 mA cm-2. First-principles calculations demonstrate that Mo doping can effectively adjust the electron redistribution of the Ni hollow sites to optimize the hydrogen adsorption-free energy for HER. Besides, in situ Raman characterization reveals the dissolving of doped Mo can promote a rapid surface reconstruction on Mo-FeNiP NTs to dynamically stable (Fe)Ni-oxyhydroxide layers, serving as the actual active species for OER. The work proposes a rational approach addressed by electron manipulation and surface reconstruction of bimetallic phosphides to regulate both the HER and OER activity.

Sfrp5 overexpression reverses oxLDL-induced lipid accumulation in HVSMCs.

Atherosclerosis (AS) is the major cause of multiple cardiovascular diseases. In addition, the lipid accumulation of human vascular smooth muscle cells (HVSMCs) can cause the occurrence of AS. Sfrp5 was known to be downregulated in atherosclerosis; however, the detailed function of Sfrp5 in HVSMCs remains unclear. Specifically, we found that Sfrp5 expression in oxLDL-treated HVSMCs was downregulated. Sfrp5 overexpression inhibited the viability of HVSMCs induced by oxLDL. In addition, oxLDL-induced proliferation and migration in HVSMCs were abolished by Sfrp5 overexpression. Sfrp5 overexpression reduced oxLDL-caused oxidative stress, lipid accumulation, and inflammation in HVSMCs. Meanwhile, oxLDL treatment increased the expressions of Wnt5a, c-Myc, and ß-catenin in HVSMCs, while this phenomenon was rescued by Sfrp5 overexpression. Furthermore, the inhibitory effect of Sfrp5 upregulation on the viability and migration of HVSMCs was reversed by R-spondin. These results indicate that Sfrp5 overexpression could reverse oxLDL-induced lipid accumulation in HVSMCs through inactivating Wnt5a/ß-catenin signaling pathway.

The complete chloroplast genome assembly of Amorphophallus tonkinensis Engler and Gehrmann 1911 from southwestern China.

Species in the Amorphophallus genus are important cash crops in many tropical and subtropical Asian countries. Although several molecular markers have been employed to determine relationships and assess genetic variation in the Amorphophallus genus, some conflicts remain in infrageneric classification and evolution. To aid in the phylogenetic research of the Amorphophallus genus, we collected one sample of Amorphophallus tonkinensis Engler and Gehrmann 1911 from southwestern China. We assembled the first chloroplast genome of this species using high-throughput sequencing. The assembled genome was 169,341 bp long with a typical quadripartite structure (GenBank accession number: PP234804). The lengths of the large single-copy region, small single-copy region, and two inverted repeats were 90,705 bp, 15,640 bp, 31,498 bp, and 31,498 bp, respectively. We annotated 129 genes across the chloroplast genome of A. tonkinensis. The phylogenetic trees suggested that the Amorphophallus species distributed in continental Asia split into two main clades. The chloroplast genome reported in our study provided valuable genomic resources for the future phylogenetic research of the Amorphophallus genus.

Beaconet: A Reference-Free Method for Integrating Multiple Batches of Single-Cell Transcriptomic Data in Original Molecular Space.

Integrating multiple single-cell datasets is essential for the comprehensive understanding of cell heterogeneity. Batch effect is the undesired systematic variations among technologies or experimental laboratories that distort biological signals and hinder the integration of single-cell datasets. However, existing methods typically rely on a selected dataset as a reference, leading to inconsistent integration performance using different references, or embed cells into uninterpretable low-dimensional feature space. To overcome these limitations, a reference-free method, Beaconet, for integrating multiple single-cell transcriptomic datasets in original molecular space by aligning the global distribution of each batch using an adversarial correction network is presented. Through extensive comparisons with 13 state-of-the-art methods, it is demonstrated that Beaconet can effectively remove batch effect while preserving biological variations and is superior to existing unsupervised methods using all possible references in overall performance. Furthermore, Beaconet performs integration in the original molecular feature space, enabling the characterization of cell types and downstream differential expression analysis directly using integrated data with gene-expression features. Additionally, when applying to large-scale atlas data integration, Beaconet shows notable advantages in both time- and space-efficiencies. In summary, Beaconet serves as an effective and efficient batch effect removal tool that can facilitate the integration of single-cell datasets in a reference-free and molecular feature-preserved mode.

Comparing Sonazoid contrast-enhanced ultrasound to contrast-enhanced CT and MRI for differentially diagnosing renal lesions: a prospective multicenter study.

PURPOSE: To evaluate the diagnostic performance of contrast-enhanced (CE) ultrasound using Sonazoid (SNZ-CEUS) by comparing with contrast-enhanced computed tomography (CE-CT) and contrast-enhanced magnetic resonance imaging (CE-MRI) for differentiating benign and malignant renal masses. MATERIALS AND METHODS: 306 consecutive patients (from 7 centers) with renal masses (40 benign tumors, 266 malignant tumors) diagnosed by both SNZ-CEUS, CE-CT or CE-MRI were enrolled between September 2020 and February 2021. The examinations were performed within 7 days, but the sequence was not fixed. Histologic results were available for 301 of 306 (98.37%) lesions and 5 lesions were considered benign after at least 2 year follow-up without change in size and image characteristics. The diagnostic performances were evaluated by sensitivity, specificity, positive predictive value, negative predictive value, and compared by McNemar's test. RESULTS: In the head-to-head comparison, SNZ-CEUS and CE-MRI had comparable sensitivity (95.60 vs. 94.51%, P = 0.997), specificity (65.22 vs. 73.91%, P = 0.752), positive predictive value (91.58 vs. 93.48%) and negative predictive value (78.95 vs. 77.27%); SNZ-CEUS and CE-CT showed similar sensitivity (97.31 vs. 96.24%, P = 0.724); however, SNZ-CEUS had relatively lower than specificity than CE-CT (59.09 vs. 68.18%, P = 0.683). For nodules > 4 cm, CE-MRI demonstrated higher specificity than SNZ-CEUS (90.91 vs. 72.73%, P = 0.617) without compromise the sensitivity. CONCLUSIONS: SNZ-CEUS, CE-CT, and CE-MRI demonstrate desirable and comparable sensitivity for the differentiation of renal mass. However, the specificity of all three imaging modalities is not satisfactory. SNZ-CEUS may be a suitable alternative modality for patients with renal dysfunction and those allergic to gadolinium or iodine-based agents.

A new tandem repeat-enriched lncRNA XLOC_008672 promotes gastric carcinogenesis by regulating G3BP1 expression.

Aberrant expression of forkhead box transcription factor 1 (FOXM1) plays critical roles in a variety of human malignancies and predicts poor prognosis. However, little is known about the crosstalk between FOXM1 and long noncoding RNAs (lncRNAs) in tumorigenesis. The present study identifies a previously uncharacterized lncRNA XLOC_008672 in gastric cancer (GC), which is regulated by FOXM1 and possesses multiple copies of tandem repetitive sequences. LncRNA microarrays are used to screen differentially expressed lncRNAs in FOXM1 knockdown GC cells, and then the highest fold downregulation lncRNA XLOC_008672 is screened out. Sequence analysis reveals that the new lncRNA contains 62 copies of 37-bp tandem repeats. It is transcriptionally activated by FOXM1 and functions as a downstream effector of FOXM1 in GC cells through in vitro and in vivo functional assays. Elevated expression of XLOC_008672 is found in GC tissues and indicates worse prognosis. Mechanistically, XLOC_008672 can bind to small nuclear ribonucleoprotein polypeptide A (SNRPA), thereby enhancing mRNA stability of Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) and, consequently, facilitating GC cell proliferation and migration. Our study discovers a new uncharacterized lncRNA XLOC_008672 involved in GC carcinogenesis and progression. Targeting FOXM1/XLOC_008672/SNRPA/G3BP1 signaling axis might be a promising therapeutic strategy for GC.

Assembly and analysis of the chloroplast genome of Amorphophallus kachinensis Engler & Gehrmann (Araceae) from Southwestern China: implications for conservation and utilization.

Konjac glucomannan consists of D-mannose and D-glucose units and is a hydrocolloid obtained from the corm of Amorphophallus species. Due to its bioactive properties, biodegradability, and hydrophilic ability, glucomannan is widely used in the fields of food, medicine, and industry. Amorphophallus species have been cultivated as cash crops in many Asian countries. Amorphophallus kachinensis Engler & Gehrmann 1911 is naturally distributed in southwestern China, Laos, and northern Thailand. To help the genetic assessment and conservation of this species, the first chloroplast genome of A. kachinensis was sequenced on the Illumina sequencing platform. We assembled the chloroplast genome using the software GetOrganelle and annotated the genome by Geseq and Cpgavas 2. The assembled chloroplast genome was 173,330 bp long, and the average GC content was 35% (GenBank accession number: PP072244). The chloroplast genome of A. kachinensis contained one large single copy, one small single copy, and two inverted repeats, with lengths of 92,030 bp, 15,118 bp, 33,091 bp, and 33,091 bp, respectively. We successfully annotated 132 genes across the genome, which was consistent with other Amorphophallus species. The phylogenetic tree indicates a sub-divergence in the Amorphophallus genus with two main genetic groups detected among eight species. The two genetic groups should be treated as distinct evolutionarily significant units when making conservation strategies. Our study enriched the chloroplast genome resources of the Amorphophallus genus and could help future phylogeographic studies, protection, and utilization of wild resources.

A phase IV study to evaluate the safety of fruquintinib in Chinese patients in real-world clinical practice.

INTRODUCTION: Fruquintinib is approved in China for patients with metastatic colorectal cancer (CRC) who progressed after 2 lines of chemotherapy. This postmarketing study was conducted to evaluate the safety of fruquintinib in the Chinese population, including previously treated patients with advanced CRC and other solid tumors. METHODS: Patients in the first cycle of fruquintinib or expected to start fruquintinib within a week were enrolled. Fruquintinib was administrated according to the label or per physicians' discretion. Patient characteristics and safety information were collected at baseline, 1 month, and 6 months after consent (or 30 days after the last dose). RESULTS: Overall, 3005 patients enrolled between April 24, 2019 and September 27, 2022. All enrolled patients received at least one dose of fruquintinib. Most patients had metastases at baseline. The median age was 60 years. More than half (64.0%) of the patients started fruquintinib at 5 mg, and the median treatment exposure was 2.7 months. Nearly one-third (32.5%) of patients with CRC received fruquintinib with concomitant antineoplastic agents. Treatment-emergent adverse events (TEAEs) leading to dose modification were reported in 626 (20.8%) patients, and 469 (15.6%) patients experienced TEAEs leading to treatment discontinuation. The most common grade ≥ 3 TEAEs were hypertension (6.6%), palmar-plantar erythrodysesthesia syndrome (2.2%), and platelet count decreased (1.0%). Combination therapy did not lead to excessive toxicities. CONCLUSIONS: The safety profile of fruquintinib in the real world was generally consistent with that in clinical studies, and the incidence of TEAEs was numerically lower than known VEGF/VEGFR inhibitor-related AEs. Fruquintinib exhibited manageable safety and tolerability in Chinese patients in the real-world setting.

Prenatal DEHP exposure induces lifelong testicular toxicity by continuously interfering with steroidogenic gene expression.

Background: Epidemiologic studies suggested the association between prenatal di-(2-ethylhexyl) phthalate (DEHP) exposure and disorders of sex development (DSD), adult male disorders, and reproductive aging. Inhibiting testosterone synthesis by interfering with steroidogenic gene expression induces testicular toxicity, however, whether prenatal DEHP exposure induces testicular toxicity through this mechanism remains uncertain. Methods: C57BL/6JGpt male mice underwent different doses (0, 100, 500, 1,000 mg/kg) of prenatal DEHP exposure during gestational day 10 to delivery day, the testicular toxicity (genital development, testosterone, semen quality, and morphology of testis tissue) in the neonatal, post-puberal and middle-aged stages was observed, and the steroidogenic gene (Lhcgr, Star, Cyp11a1, Cyp17a1, Hsd17b3, and Hsd3b2) expression was analyzed by quantitative polymerase chain reaction (qPCR) and Western blot (WB). The interference of steroidogenic gene expression in TM3 cells after mono-(2-ethylhexyl) phthalate (MEHP) exposure was also explored for verification. Results: Prenatal DEHP exposure induced immediate testicular injury in the neonatal stage [reduced anogenital distance (AGD) and intratesticular testosterone], DSD in the post-puberal stage (poor genital development), and reproductive aging in the middle-aged stage (obesity, reduced testosterone and semen quality, and atrophic seminiferous tubules), especially in the high dose. Prenatal DEHP exposure continuously interfered with steroidogenic gene expression (Hsd3b2, Hsd17b3) in RNA and protein levels. MEHP inhibited testosterone synthesis of TM3 cells by interfering with steroidogenic gene expression (Hsd3b2, Hsd17b3) in RNA and protein levels. Conclusions: Prenatal DEHP exposure induces lifelong testicular toxicity by continuously interfering with steroidogenic gene expression, thus indicating the association between prenatal exposure and DSD, adult male disorders, and reproductive aging.

Anti-aggregation colorimetric sensing of cysteine using silver nanoparticles in the presence of Pb2.

Using silver nitrate as the silver source and sodium borohydride as the reducing agent, we synthesized negatively charged silver nanoparticles (AgNPs). Subsequently, the AgNPs solution was mixed with positively charged lead ions, resulting in AgNPs aggregation via electrostatic interactions. This led to a color change in the solution from yellow to purple and eventually to blue-green. Our study focused on a colorimetric method that exhibited high selectivity and sensitivity in detecting cysteine using AgNPs-Pb2+ as a sensing probe. Upon the introduction of cysteine to the AgNPs-Pb2+ system, the absorbance of AgNPs increased at 396 nm and decreased at 520 nm. The formation of a complex between cysteine and lead ions prevented the aggregation of silver nanoparticles, enabling the colorimetric detection of cysteine. The relationship between the concentration of ΔA396/A520 and cysteine showed linearity within the range of 0.01 to 0.1 µM; the regression equation of the calibration curve is ΔA396/A520 = 9.0005c - 0.0557 (c: µM), with an R2 value of 0.9997. The detection limit was found to be 3.8 nM (S/N = 3). This method demonstrated exceptional selectivity and sensitivity for cysteine and was effectively used for the determination of cysteine in urine. Our findings offer a new perspective for the future advancement of anti-aggregation silver nanocolorimetry.

Recombinant human IL-37 attenuates acute cardiac allograft rejection in mice.

BACKGROUND: Allograft rejection remains a major obstacle to long-term graft survival. Although previous studies have demonstrated that IL-37 exhibited significant immunomodulatory effects in various diseases, research on its role in solid organ transplantation has not been fully elucidated. In this study, the therapeutic effect of recombinant human IL-37 (rhIL-37) was evaluated in a mouse cardiac allotransplantation model. METHODS: The C57BL/6 recipients mouse receiving BALB/c donor hearts were treated with rhIL-37. Graft pathological and immunohistology changes, immune cell populations, and cytokine profiles were analyzed on postoperative day (POD) 7. The proliferative capacities of Th1, Th17, and Treg subpopulations were assessed in vitro. Furthermore, the role of the p-mTOR pathway in rhIL-37-induced CD4+ cell inhibition was also elucidated. RESULTS: Compared to untreated groups, treatment of rhIL-37 achieved long-term cardiac allograft survival and effectively alleviated allograft rejection indicated by markedly reduced infiltration of CD4+ and CD11c+ cells and ameliorated graft pathological changes. rhIL-37 displayed significantly less splenic populations of Th1 and Th17 cells, as well as matured dendritic cells. The percentages of Tregs in splenocytes were significantly increased in the therapy group. Furthermore, rhIL-37 markedly decreased the levels of TNF-α and IFN-γ, but increased the level of IL-10 in the recipients. In addition, rhIL-37 inhibited the expression of p-mTOR in CD4+ cells of splenocytes. In vitro, similar to the in vivo experiments, rhIL-37 caused a decrease in the proportion of Th1 and Th17, as well as an increase in the proportion of Treg and a reduction in p-mTOR expression in CD4+ cells. CONCLUSIONS: We demonstrated that rhIL-37 effectively suppress acute rejection and induce long-term allograft acceptance. The results highlight that IL-37 could be novel and promising candidate for prevention of allograft rejection.

The complete chloroplast genome assembly of Castanopsis orthacantha Franch. 1899 (Fagaceae) in Southwestern China.

Castanopsis orthacantha Franch. 1899 is one representative tree species distributed in the evergreen broad-leaved forests of southwestern China. This species is an important source of timber for manufacturing furniture, floors, and paper. It also plays a significant role in maintaining ecological balance and stability. To help with the genetic diversity assessment of C. orthacantha, we sequenced and assembled the first complete chloroplast genome. The length of the chloroplast genome was 160,588 bp, with a typical quadripartite structure (GenBank accession no. OR900101). The large single-copy (LSC), small single-copy (SSC), and two inverted repeats (IRs) were 90,237 bp, 18,953 bp, and 25,699 bp in length, respectively. We annotated one hundred and thirty genes across the chloroplast genome, including 86 protein-coding genes (79 are unique), 37 tRNA genes (29 are unique), and eight rRNA genes (four are unique). Seventeen genes had one intron, and four were detected with two introns. The maximum likelihood phylogeny suggested that C. orthacantha, C. lamontii, C. sclerophylla, and C. hainanensis formed a clade with a high bootstrap value. This newly sequenced chloroplast genome assembly will aid in the population genetic and phylogenetic studies of Castanopsis species in the future.

Discovery of new N-Phenylamide Isoxazoline derivatives with high insecticidal activity and reduced honeybee toxicity.

Isoxazoline is a novel structure with strong potential for controlling agricultural insect pests, but its high toxicity to honeybees limits its development in agriculture. Herein, a series of N-phenylamide isoxazoline derivatives with low honeybee toxicity were designed and synthesized using the intermediate derivatization method. Bioassay results showed that these compounds exhibited good insecticidal activity. Compounds 3b and 3f showed significant insecticidal effects against Plutella xylostella (P. xylostella) with median lethal concentrations (LC50) of 0.06 and 0.07 mg/L, respectively, comparable to that of fluralaner (LC50 = 0.02 mg/L) and exceeding that of commercial insecticide fluxametamide (LC50 = 0.52 mg/L). It is noteworthy that the acute honeybee toxicities of compounds 3b and 3f (LD50 = 1.43 and 1.63 µg/adult, respectively) were significantly reduced to 1/10 of that of fluralaner (LD50 = 0.14 µg/adult), and were adequate or lower than that of fluxametamide (LD50 = 1.14 µg/adult). Theoretical simulation using molecular docking indicates that compound 3b has similar binding modes with fluralaner and a similar optimal docking pose with fluxametamide when binding to the GABA receptor, which may contribute to its potent insecticidal activity and relatively low toxicity to honey bees. This study provides compounds 3b and 3f as potential new insecticide candidates and provides insights into the development of new isoxazoline insecticides exhibiting both high efficacy and environmental safety.