Migration and transformation behaviors of antibiotics in water-sediment system under simulated light and wind waves.

Antibiotics can generally be detected in the water-sediment systems of lakes. However, research on the migration and transformation of antibiotics in water-sediment systems based on the influences of light and wind waves is minimal. To address this research gap, we investigated the specific impacts of light and wind waves on the migration and transformation of three antibiotics, norfloxacin (NOR), trimethoprim (TMP), and sulfamethoxazole (SMX), under simulated light and wind waves disturbance conditions in a water-sediment system from Taihu Lake, China. In the overlying water, NOR was removed the fastest, followed by TMP and SMX. Compared to the no wind waves groups, the disturbance of big wind waves reduced the proportion of antibiotics in the overlying water. The contributions of light and wind waves to TMP and SMX degradation were greater than those of microbial degradation. However, the non-biological and biological contributions of NOR to degradation were almost equal. Wind waves had a significant impact on the microbial community changes in the sediment, especially in Methylophylaceae. These results verified the influence of light and wind waves on the migration and transformation of antibiotics, and provide assistance for the risk of antibiotic occurrence in water and sediments.

Metal-ion-controlled hydrogel dressing with enhanced adhesive and antibacterial properties for accelerated wound healing.

In order to improve the wound repair environment, this research has successfully developed a new multifunctional hydrogel dressing, which has strong adaptability and can accelerate wound healing. Pioneering the development of metal-ion-controlled hydrogel dressings, this research integrates dopamine and imidazole double crosslinked networks with metal-ion coordination. The resulting hydrogel dressing exhibits a notable antibacterial effect and exceptional mechanical properties, withstanding pressures of up to 12 kPa, tensions of 25 kPa, and maintaining skin adhesion at 6 kPa. Furthermore, the dressing can self-heal within only 7-8 s post-injection. Impressively, the hydrogel achieves complete biodegradation within a short timeframe (37 h). Notably, the use of various metal ions facilitates painless peeling during the degradation period, perfectly aligning with the requirements of an ideal wound dressing. This study has made significant progress in the fields of trauma repair and materials, providing strong solutions for dealing with harsh post-traumatic environments.

The role of FPR2-mediated ferroptosis in formyl peptide-induced acute lung injury against endothelial barrier damage and protective effect of the mitochondria-derived peptide MOTS-c.

BACKGROUND: Acute lung injury (ALI) has garnered significant attention in the field of respiratory and critical care due to its high mortality and morbidity, and limited treatment options. The role of the endothelial barrier in the development of ALI is crucial. Several bacterial pathogenic factors, including the bacteria-derived formyl peptide (fMLP), have been implicated in damaging the endothelial barrier and initiating ALI. However, the mechanism by which fMLP causes ALI remains unclear. In this study, we aim to explore the mechanisms of ALI caused by fMLP and evaluate the protective effects of MOTS-c, a mitochondrial-derived peptide. METHODS: We established a rat model of ALI and a human pulmonary microvascular endothelial cell (HPMVEC) model of ALI by treatment with fMLP. In vivo experiments involved lung histopathology assays, assessments of inflammatory and oxidative stress factors, and measurements of ferroptosis-related proteins and barrier proteins to evaluate the severity of fMLP-induced ALI and the type of tissue damage in rats. In vitro experiments included evaluations of fMLP-induced damage on HPMVEC using cell activity assays, assessments of inflammatory and oxidative stress factors, measurements of ferroptosis-related proteins, endothelial barrier function assays, and examination of the key role of FPR2 in fMLP-induced ALI. We also assessed the protective effect of MOTS-c and investigated its mechanism on the fMLP-induced ALI in vivo and in vitro. RESULTS: Results from both in vitro and in vivo experiments demonstrate that fMLP promotes the expression of inflammatory and oxidative stress factors, activates ferroptosis and disrupts the vascular endothelial barrier, ultimately contributing to the development and progression of ALI. Mechanistically, ferroptosis mediated by FPR2 plays a key role in fMLP-induced injury, and the Nrf2 and MAPK pathways are involved in this process. Knockdown of FPR2 and inhibition of ferroptosis can attenuate ALI induced by fMLP. Moreover, MOTS-c could protect the vascular endothelial barrier function by inhibiting ferroptosis and suppressing the expression of inflammatory and oxidative stress factors through Nrf2 and MAPK pathways, thereby alleviating fMLP-induced ALI. CONCLUSION: Overall, fMLP disrupts the vascular endothelial barrier through FPR2-mediated ferroptosis, leading to the development and progression of ALI. MOTS-c demonstrates potential as a protective treatment against ALI by alleviating the damage induced by fMLP.

MicroRNA-508-3p regulates the proliferation of human lung cancer cells by targeting G1 to S phase transition 1 (GSPT1) protein.

PURPOSE: Due to its crucial cancer regulatory role, microRNA-508-3p has been reported as a potential therapeutic anticancer molecular target. The present work encompassed the molecular characterization of microRNA-508-3p in lung cancer emphasizing on understanding the possible mechanism of its regulatory action. METHODS: qRT-PCR was performed to estimate the relative gene expression of microRNA-508-p in the tissue samples. The proliferation of cancer cells was determined by cell counting kit-8. The colony formation from cancer cells was analyzed by clonogenic assay. Mitotic phase distribution was understood by employing the flow cytometric technique. Edu-Hoechst staining was used for the assessment of cell viability. In silico analysis and dual-luciferase assay were used for target identification of microRNA-508-3p in lung cancer. Immunofluorescence and western blotting studies were carried out for relative protein expression. The rat models were used for performing the in vivo experimental procedures. RESULTS: The study showed the significant down-regulation of microRNA-508-3p in lung cancer. The lower expression levels of microRNA-508-3p were shown to be associated with poor survival of lung cancer patients. The over-expression of microRNA-508-3p was found to decline the proliferation and viability of cancer cells together with the induction of mitotic cell cycle arrest at G1 by targeting G1 to S phase transition 1 (GSPT1) protein. MicroRNA-508-3p up-regulation inhibited the in vivo tumor growth in rat models. CONCLUSION: Our study identifies miR-508-3p as a pivotal regulator of lung cancer cell proliferation by targeting the GSPT1 protein. This highlights its potential as a tumor suppressor and a therapeutic target for lung cancer. Our findings offer mechanistic insights into miRNA-mediated cancer progression, prompting further research in this intricate regulatory network.

Influence by varying organic matter content and forms in suspended particulate matter: impacts on the adsorption of tetracycline and norfloxacin.

Antibiotics are commonly detected in natural waters. The organic matter (OM) in suspended particulate matter (SPM) has a critical impact on the adsorption of antibiotics in water. We investigated the contribution of OM content and form to the adsorption of tetracycline (TC) and norfloxacin (NOR) in the SPM of Taihu Lake. To change the content and form of OM in SPM, the samples were subjected to pyrolysis at 505 ˚C and oxidization with H2O2, respectively. Combustion almost completely removed OM, while oxidation removed most of the OM and transformed the remaining OM. Regardless of whether the OM changed or not, the adsorption of NOR and TC by SPM was more in line with the pseudo-second-order kinetic model instead of pseudo-first-order. The fitting of the intraparticle diffusion model showed that the removal of OM had a certain degree of change in the adsorption process. The isothermal adsorption of TC in all samples was more in line with the Temkin model. The isothermal adsorption of NOR in the oxidized sample conformed to the Temkin model, while it conformed to the Langmuir model in the original sample and the sample removed OM via combustion. The adsorption capacity of SPM with almost complete removal of OM significantly decreased, while conversely, the adsorption capacity of SPM after oxidation increased. This indicates that both the content and form of OM affect the adsorption of antibiotics by SPM, and the form of OM has a greater impact. The contribution of OM to NOR adsorption was greater than that of TC. In conclusion, the results verify the importance of OM in adsorbing antibiotics onto SPM, which may provide basic data for antibiotic migration in surface water.

Exogenous melatonin enhances the tolerance of tiger nut (Cyperus esculentus L.) via DNA damage repair pathway under heavy metal stress (Cd2+) at the sprout stage.

Heavy metal (HM) stress is a non-negligible abiotic stress that seriously restricts crop yield and quality, while the sprout stage is the most sensitive to stress and directly impacts the growth and development of the later stage. Melatonin (N-acetyl-5-methoxytryptamine), as an exogenous additive, enhances stress resistance due to its ability to oxidize and reduce. However, few reports on exogenous melatonin to tiger nuts under HM stress have explored whether exogenous melatonin enhances plants' resistance to heavy metals. Here, "Jisha 2″ was used as material, with a stress concentration of 5 mg/L and 100 µmol/L of CdCl2 to explore whether exogenous melatonin enhances plant resistance and molecular mechanism. The result revealed that stress limits growth, while melatonin alleviated the sprout damage under stress from the phenotypes. Moreover, stress-enhanced reactive oxygen species (ROS) accumulation and membrane lipid peroxidation, while melatonin-increased ROS reduce damage via the analysis of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) and malondialdehyde (MDA) content, hydrogen peroxide (H2O2), superoxide anion (O2-), and Electrolyte leakage (El). Further results indicated that HM leads to DNA damage while exogenous melatonin will repair the damage by analyzing random amplified polymorphic DNA (RAPD), DNA cross-linking, 8-hydroxy-20-deoxyguanine level, and relative density of apurinic sites. Furthermore, gene expression in the DNA-repaired pathway exhibited similar results. These results applied that exogenous melatonin released the hurt caused by HM stress, with DNA repair and ROS balance serving as candidate pathways. This study elucidated the mechanism of melatonin's influence and provided theoretical insights into its application in tiger nuts.

Advances in Functional Hydrogel Wound Dressings: A Review.

One of the most advanced, promising, and commercially viable research issues in the world of hydrogel dressing is gaining functionality to achieve improved therapeutic impact or even intelligent wound repair. In addition to the merits of ordinary hydrogel dressings, functional hydrogel dressings can adjust their chemical/physical properties to satisfy different wound types, carry out the corresponding reactions to actively create a healing environment conducive to wound repair, and can also control drug release to provide a long-lasting benefit. Although a lot of in-depth research has been conducted over the last few decades, very few studies have been properly summarized. In order to give researchers a basic blueprint for designing functional hydrogel dressings and to motivate them to develop ever-more intelligent wound dressings, we summarized the development of functional hydrogel dressings in recent years, as well as the current situation and future trends, in light of their preparation mechanisms and functional effects.

AQP8 may affect glioma proliferation and growth by regulating GSK-3ß phosphorylation and nuclear transport of ß-catenin.

PURPOSE: The purpose of this work is to examine the impact of AQP8 on the proliferation and development of human glioma cell lines A172 and U251 and to determine if aquaporin 8 (AQP8) is associated with GSK-3ß phosphorylation and nuclear transport of ß-catenin in the Wnt signaling pathway. METHODS: AQP8 knockdown cell lines were constructed using a CRISPR/Cas9 double vector lentivirus infection. SAM/dCas9 was used to construct AQP8 overexpression cell lines and the CV084 lentivirus vector was used to construct AQP8 rescue cell lines. AQP8 and its mRNA, and phosphorylated GSK-3ß, ß-catenin, and other related proteins, were detected using western blot and qRT-PCR. Glioma cell apoptosis was detected using Hoechst 33342 dye. The migration of glioma cells was discovered using a wound healing assay. ß-catenin localization in cells was detected using immunofluorescence staining. RESULTS: The proliferative and migratory capacities of A172 and U251 cells were significantly enhanced after AQP8 overexpression. The Wnt signaling pathways appeared to have higher levels of phosphorylated GSK-3ß and ß-catenin, and a rise in the fluorescence intensity ratio of ß-catenin in the nucleus and cytoplasm, which suggests that ß-catenin translocated into the nucleus, while AQP8 knockdown produced the opposite effect. Further, overexpression of AQP8 in AQP8 knockdown cell lines rescued the reduction of related protein levels caused by AQP8 knockdown. CONCLUSION: High AQP8 expression promotes proliferation and growth of glioma cells, a process associated with phosphorylation of GSK-3ß and nuclear translocation of ß-catenin.

MacFrag: segmenting large-scale molecules to obtain diverse fragments with high qualities.

SUMMARY: Construction of high-quality fragment libraries by segmenting organic compounds is an important part of the drug discovery paradigm. This article presents a new method, MacFrag, for efficient molecule fragmentation. MacFrag utilized a modified version of BRICS rules to break chemical bonds and introduced an efficient subgraphs extraction algorithm for rapid enumeration of the fragment space. The evaluation results with ChEMBL dataset exhibited that MacFrag was overall faster than BRICS implemented in RDKit and modified molBLOCKS. Meanwhile, the fragments acquired through MacFrag were more compliant with the 'Rule of Three'. AVAILABILITY AND IMPLEMENTATION: https://github.com/yydiao1025/MacFrag. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Two new species of the genus Diestramima from China (Orthoptera: Rhaphidophoridae: Aemodogryllinae).

The genus Diestramima comprises 41 species from Asia with 31 species distributed in China. In this study, we reconstruct the phylogeny tree of Diestramima species by maximum likelihood and Bayesian inference based on three mitochondrial genes (COI, 12S and 16S). The result indicates that the phylogenetic results are coherent with that based on five molecular markers (COI, 12S, 16S, 18S and 28S). Moreover, two new species, D. pingmengensis sp. nov. He & Zong and D. gulinjingensis. sp. nov. Zong & He are described. Their validities are also supported by morphological features. Furthermore, D. sichuanensis Zhu & Shi, 2022 is treated as a junior synonym of D. guangxiensis Qin, Wang, Liu & Li, 2016 based on both morphological and molecular features.

Anomalous depinning of magnetic domain walls within the ferromagnetic phase of the Weyl semimetal Co3Sn2S2.

We report bulk magnetization measurements and spatially resolved measurements of magnetic domains inCo3Sn2S2single crystals. The results indicate that a previously reported magnetic anomaly around 130 K is due to an anomalous domain wall depinning upon cooling. Our measurements also reveal a hysteresis between field-cooled-cooling and field-cooled-warming magnetization curves acquired under a constant magnetic field below 300 Oe. This observation rules out the possibility that the anomaly stems from a second-order phase transition. Our results further suggest that changes in the shape of hysteresis loops from 5 to 170 K are caused by an unusual temperature-dependent domain nucleation field that changes sign around 130 K. The Kerr rotation images of the magnetic domains confirm that the domain walls depin between 120 and 140 K.

e-TSN: an interactive visual exploration platform for target-disease knowledge mapping from literature.

Target discovery and identification processes are driven by the increasing amount of biomedical data. The vast numbers of unstructured texts of biomedical publications provide a rich source of knowledge for drug target discovery research and demand the development of specific algorithms or tools to facilitate finding disease genes and proteins. Text mining is a method that can automatically mine helpful information related to drug target discovery from massive biomedical literature. However, there is a substantial lag between biomedical publications and the subsequent abstraction of information extracted by text mining to databases. The knowledge graph is introduced to integrate heterogeneous biomedical data. Here, we describe e-TSN (Target significance and novelty explorer, http://www.lilab-ecust.cn/etsn/), a knowledge visualization web server integrating the largest database of associations between targets and diseases from the full scientific literature by constructing significance and novelty scoring methods based on bibliometric statistics. The platform aims to visualize target-disease knowledge graphs to assist in prioritizing candidate disease-related proteins. Approved drugs and associated bioactivities for each interested target are also provided to facilitate the visualization of drug-target relationships. In summary, e-TSN is a fast and customizable visualization resource for investigating and analyzing the intricate target-disease networks, which could help researchers understand the mechanisms underlying complex disease phenotypes and improve the drug discovery and development efficiency, especially for the unexpected outbreak of infectious disease pandemics like COVID-19.

Upregulation of miR-664a-3p Ameliorates Calcific Aortic Valve Disease by Inhibiting the BMP2 Signaling Pathway.

The development of calcific aortic valve disease (CAVD) is a complex process of ectopic calcification involving various factors that lead to aortic valve stenosis, hemodynamic changes, and, in severe cases, even sudden death. Currently, aortic valve replacement is the only effective method. The osteogenic differentiation of aortic valve interstitial cells (AVICs) is one of the key factors of valve calcification. Emerging evidence suggests that bone morphogenetic protein 2 (BMP2) can induce the proosteogenic activation of AVICs. However, the regulatory mechanism underlying this activation in AVICs is unclear. In the present study, we elucidated through high-throughput RNA sequencing and RT-qPCR that miR-664a-3p was evidently downregulated in the calcific aortic valve. We also proved that miR-664a-3p was involved in regulating osteogenic differentiation in AVICs. Target prediction analysis and dual-luciferase reporter gene assay confirmed that miR-664a-3p is preferentially bound to BMP2. Furthermore, the effect of the miR-664a-3p/BMP2 axis on osteogenic differentiation in AVICs was examined using the gain- and loss-of-function approach. Finally, we constructed a mouse CAVD model and verified the effect of the miR-664a-3p/BMP2 axis on the aortic valve calcification leaflets in vivo. In conclusion, miR-664a-3p regulates osteogenic differentiation in AVICs through negative regulation of BMP2, highlighting that miR-664a-3p may be a potential therapeutic target for CAVD.

Multi-modal chemical information reconstruction from images and texts for exploring the near-drug space.

Identification of new chemical compounds with desired structural diversity and biological properties plays an essential role in drug discovery, yet the construction of such a potential space with elements of 'near-drug' properties is still a challenging task. In this work, we proposed a multimodal chemical information reconstruction system to automatically process, extract and align heterogeneous information from the text descriptions and structural images of chemical patents. Our key innovation lies in a heterogeneous data generator that produces cross-modality training data in the form of text descriptions and Markush structure images, from which a two-branch model with image- and text-processing units can then learn to both recognize heterogeneous chemical entities and simultaneously capture their correspondence. In particular, we have collected chemical structures from ChEMBL database and chemical patents from the European Patent Office and the US Patent and Trademark Office using keywords 'A61P, compound, structure' in the years from 2010 to 2020, and generated heterogeneous chemical information datasets with 210K structural images and 7818 annotated text snippets. Based on the reconstructed results and substituent replacement rules, structural libraries of a huge number of near-drug compounds can be generated automatically. In quantitative evaluations, our model can correctly reconstruct 97% of the molecular images into structured format and achieve an F1-score around 97-98% in the recognition of chemical entities, which demonstrated the effectiveness of our model in automatic information extraction from chemical patents, and hopefully transforming them to a user-friendly, structured molecular database enriching the near-drug space to realize the intelligent retrieval technology of chemical knowledge.

Identification of molecular subtypes, risk signature, and immune landscape mediated by necroptosis-related genes in non-small cell lung cancer.

Background: Non-small cell lung cancer (NSCLC) is a highly heterogeneous malignancy with an extremely high mortality rate. Necroptosis is a programmed cell death mode mediated by three major mediators, RIPK1, RIPK3, and MLKL, and has been shown to play a role in various cancers. To date, the effect of necroptosis on NSCLC remains unclear. Methods: In The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we downloaded transcriptomes of lung adenocarcinoma (LUAD) patients and their corresponding clinicopathological parameters. We performed multi-omics analysis using consensus clustering based on the expression levels of 40 necroptosis-related genes. We constructed prognostic risk models and used the receiver operating characteristic (ROC) curves, nomograms, and survival analysis to evaluate prognostic models. Results: With the use of consensus clustering analysis, two distinct subtypes of necroptosis were identified based on different mRNA expression levels, and cluster B was found to have a better survival advantage. Correlation results showed that necroptosis was significantly linked with clinical features, overall survival (OS) rate, and immune infiltration. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis confirmed that these differential genes were valuable in various cellular and biological functions and were significantly enriched in various pathways such as the P53 signaling pathway and cell cycle. We further identified three genomic subtypes and found that gene cluster B patients had better prognostic value. Multivariate Cox analysis identified the 14 best prognostic genes for constructing prognostic risk models. The high-risk group was found to have a poor prognosis. The construction of nomograms and ROC curves showed stable validity in prognostic prediction. There were also significant differences in tumor immune microenvironment, tumor mutational burden (TMB), and drug sensitivity between the two risk groups. The results demonstrate that the 14 genes constructed in this prognostic risk model were used as tumor prognostic biomarkers to guide immunotherapy and chemotherapy. Finally, we used qRT-PCR to validate the genes involved in the signature. Conclusion: This study promotes our new understanding of necroptosis in the tumor microenvironment of NSCLC, mines prognostic biomarkers, and provides a potential value for guiding immunotherapy and chemotherapy.

Effect of cryopreservation on A172 and U251 glioma cells infected with lentiviral vectors designed for CRISPR/Cas9-mediated aquaporin-8 knock-out.

Among the three existing targeted gene editing technologies, zinc-finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats-CRISPR-associated 9 (CRISPR-Cas9), the latter is widely used owing to its simplicity, efficiency, and low cost. Here, we routinely infected A172 and U251 cells with lentiviral vectors, in which aquaporin-8 (AQP8) was knocked out using CRISPR/Cas9. Our results indicated that cryopreservation did not significantly alter the viral infection efficiency, but influenced AQP8 expression in the infected cells at both protein and mRNA levels compared with the non-cryopreserved samples. Further, AQP8 expression at protein and mRNA levels in recovered cryopreserved infected cells did not significantly differ from those in the blank and negative controls, indicating that the lentivirus was still infectious at low temperatures. However, it failed to release the AQP8-targeting guide RNA in the infected cells, or the guide RNA was released, but underwent changes that caused it to malfunction in the cells with CRISPR/Cas9-mediated AQP8 knock-out. Our findings possibly provide some insights into the reliability of lentiviruses as CRISPR/Cas9 vectors.

Integrative Analysis of m6A RNA Methylation Regulators and the Tumor Immune Microenvironment in Non-Small-Cell Lung Cancer.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is a major component of lung cancer and is significantly correlated with poor prognosis. N6-methyladenosine (m6A) RNA methylation is closely related to the occurrence, progression, and prognosis of cancer. The potential biological functions and mechanisms of m6A RNA methylation in the immune microenvironment are still unclear. METHODS: We assessed m6A RNA methylation modification patterns in 1326 NSCLC patient samples based on 20 m6A regulators, linking these clusters to the tumor microenvironment and immune cell infiltration. The m6Ascore was created to quantify the m6A modification patterns of individual tumors. We then assessed the value of NSCLC patients in terms of clinical prognosis and immunotherapy response. RESULTS: According to different mRNA expression levels, two different m6A clusters were identified. m6A aggregation was significantly associated with clinical prognostic characteristics, the tumor microenvironment, and immune-related biological processes. Fifteen differential genes were screened based on these two m6A clusters, and to further investigate the mechanisms of action of these differential genes, they were subjected to unsupervised clustering analysis, which classified them into four different genomic isoforms. Prognostic analysis indicated that the survival advantage of the m6A gene cluster A modification mode was significantly prominent. We continued to construct the m6Ascore, which was used as a scoring tool to evaluate tumor typing, immunity, and prognosis. Patients with a low m6Ascore showed a significant survival advantage, and the group with a low m6Ascore had a better prognosis predicted by immunotherapy. The anti-PD-1/L1 immunotherapy cohort showed that a lower m6Ascore was associated with higher efficacy of immunotherapy. CONCLUSIONS: The results suggest that m6A RNA methylation regulators make an important difference in the tumor immune microenvironment of patients with NSCLC. m6A gene characterization and the construction of the m6Ascore provide us with a richer understanding of m6A RNA methylation modification patterns in NSCLC patients and help to predict clinical prognosis and immunotherapeutic response.

Discovery of Pteridine-7(8H)-one Derivatives as Potent and Selective Inhibitors of Bruton's Tyrosine Kinase (BTK).

Bruton's tyrosine kinase (BTK) is an attractive therapeutic target in the treatment of cancer, inflammation, and autoimmune diseases. Covalent and noncovalent BTK inhibitors have been developed, among which covalent BTK inhibitors have shown great clinical efficacy. However, some of them could produce adverse effects, such as diarrhea, rash, and platelet dysfunction, which are associated with the off-target inhibition of ITK and EGFR. In this study, we disclosed a series of pteridine-7(8H)-one derivatives as potent and selective covalent BTK inhibitors, which were optimized from 3z, an EGFR inhibitor previously reported by our group. Among them, compound 24a exhibited great BTK inhibition activity (IC50 = 4.0 nM) and high selectivity in both enzymatic (ITK >250-fold, EGFR >2500-fold) and cellular levels (ITK >227-fold, EGFR 27-fold). In U-937 xenograft models, 24a significantly inhibited tumor growth (TGI = 57.85%) at a 50 mg/kg dosage. Accordingly, 24a is a new BTK inhibitor worthy of further development.

Perlodinellashennongjia sp. nov., a new species of Perlodinella Klapálek (Plecoptera, Perlodidae) from the central area of China.

Background: Perlodinella Klapálek, 1912 is a small stonefly genus in the Palearctic areas of China and its biodiversity is underestimated. New information: This paper reports a new species of Perlodinella, Perlodinellashennongjia sp. nov. in the Dajiuhu National Wetland Park of Shennongjia Forestry District, Hubei Province, central China. The description and illustrations of the new species are provided, based on male adults, female adults and eggs. The new species can be distinguished from its congeners by the characters of male and female genitalia and the egg structure.