Degradation and transformation mechanisms of pungent substances in huajiao (Zanthoxylum bungeanum) oil during storage: Induced by ultraviolet irradiation.

The pungency of huajiao (scientifically known as Zanthoxylum bungeanum) oil (ZBO), a crucial seasoning oil, is notably influenced by storage conditions, an aspect insufficiently explored in current research. Through the use of high-performance liquid chromatography and liquid chromatography-mass spectrometry, this study systematically investigated the stability of pungent compounds in ZBO under various storage conditions. It also elucidated the degradation and transformation mechanisms of these substances when exposed to ultraviolet (UV) irradiation. The results underscore elevated temperature, light exposure, oxygen, and storage duration as pivotal factors influencing compound degradation, with UV light emerging as the primary driving force. After 48 h of UV exposure, the primary pungent compound, hydroxy-α-sanshool, experienced a significant loss of 85.49%, indicating a pronounced inclination towards isomerization and oxidation. Notably, this study reveals, for the first time, the possible degradation-transformation pattern of hydroxy-γ-sanshool: a mutual conversion with hydroxy-γ-isosanshool and isomerization to (2E,4E,8Z,10E,12Z)-N-(2-hydroxy-2-methylpropyl) tetradeca-2,4,8,10,12-pentaenamide.

Two doses of fosaprepitant included prophylactic treatment for the three-day cisplatin-based chemotherapy induced nausea and vomiting.

PURPOSE: Neurokinin 1 receptor antagonists included prophylactic treatment was recommended for patients who receive one-day cisplatin chemotherapy. It is unclear whether the prolonged administration of fosaprepitant is effective for three-day cisplatin-based chemotherapy induced nausea and vomiting (CINV). We aim to explore the prophylactic antiemetic efficacy and safety of two doses of fosaprepitant included regimen in the patients receiving multiple-day cisplatin chemotherapy. METHODS: This randomized, parallel-group, open-labelled study was conducted in nine hospitals between February 2021 and February 2023. Patients diagnosed as lung cancer and chemotherapy naive were screened. Eligible participants were scheduled to be treated with highly emetogenic chemotherapy regimen which including three days of cisplatin. Then they were randomly divided into the experimental group (two doses of fosaprepitant, Group 2DF) and the control group (one dose of fosaprepitant, Group C). The primary endpoints included the safety and the average none CINV days (NCDs). This study was registered on the website of chictr.org.cn, number ChiCTR2100042665. RESULTS: Overall, 204 participants were randomly assigned, and 198 patients were analyzed. No statistical difference in adverse events was found between the two groups. All treatment-related adverse effects for fosaprepitant observed were of grade 1-2. The average NCDs of Group 2DF was significantly more than Group C (18.21 ± 3.40 days vs 16.14 ± 5.20 days, P = 0.001). Furthermore, the better life function score was achieved in Group 2DF according to FLIE questionnaire. CONCLUSION: The administration of two-dose fosaprepitant was safe and more effective than one dose in protecting patients from CINV induced by three-day cisplatin included chemotherapy.

A gelatin methacryloyl (GelMA) treated with gallic acid and coated with specially designed nanoparticles derived from ginseng enhances the healing of wounds in diabetic rats.

Due to persistent inflammation and oxidative stress reactions, achieving drug absorption in diabetic wounds is challenging. To overcome this problem, our article presents a composite hydrogel, GelMA-GA/DMOG@GDNP, which consists of gelatin methacryloyl (GelMA) treated with gallic acid (GA) and encapsulating ginseng-derived nanoparticles (GDNPs) loaded with dimethyloxallyl glycine (DMOG). The composite hydrogel demonstrates excellent biocompatibility. In laboratory settings, the hydrogel inhibits the production of nitric oxide synthase 2 (iNOS) in mouse immune cells (RAW264.7 cells), enhances the growth and migration of mouse connective tissue cells (L929 cells) and human endothelial cells (HUVECs), and promotes tube formation in HUVECs. In a rat model of type 1 diabetes-induced wounds, the composite hydrogel attenuates inflammatory reactions, facilitates the formation of fibres and blood vessels, accelerates wound healing, and elucidates specific pathway mechanisms through transcriptome sequencing. Therefore, the GelMA-GA/DMOG@GDNP hydrogel can serve as a safe and efficient wound dressing to regulate the inflammatory response, promote collagen fiber and blood vessel formation, and accelerate wound healing. These findings suggest that utilizing this multifunctional engineered nanoparticle-loaded hydrogel in a clinical setting may be a promising strategy for diabetic wound healing.

ZBTB20 suppresses tumor growth in glioblastoma through activating the TET1/FAS/caspase­3 pathway.

Zinc finger and BTB domain containing 20 (ZBTB20) is a key transcription repressor that regulates multiple physiological and pathophysiological processes. Thus far, the role of ZBTB20 in glioblastoma (GBM), a World Health Organization grade IV glioma, remains unclear. In the present study, the expression profile data of ZBTB20 in GBM tissues from public databases was analyzed. It was found that ZBTB20 expression in GBM tissues was significantly lower than that measured in lower grade glioma tissues. Furthermore, patients with GBM with lower ZBTB20 expression were associated with a shorter overall survival time. Gain- and loss-of-function experiments in GBM cells were also performed. The results demonstrated that ZBTB20 overexpression decreased GBM cell proliferation, while ZBTB20 knockdown significantly enhanced it. Cell cycle analysis showed the ZBTB20 overexpression may have inhibited proliferation through cell cycle arrest at the G2/M phase, while ZBTB20 knockdown increased the percentages of cells in both the S phase and G2/M phase. Ten-eleven translocation 1 (TET1) is an important tumor suppressor involved in the formation of various types of tumor, and it was upregulated in ZBTB20-overexpressing GBM cells. It was further demonstrated that ZBTB20 activated the TET1/FAS/caspase-3 pathway. The results of the present study therefore indicated the potential role of ZBTB20 as a tumor suppressor and therapeutic target for GBM.

Pleiotropic effects of nitric oxide sustained-release system for peripheral nerve repair.

The regenerative microenvironment after peripheral nerve injury is imbalanced and difficult to rebalance, which is mainly affected by inflammation, oxidative stress, and inadequate blood supply. The difficulty in remodeling the nerve regeneration microenvironment is the main reason for slow nerve regeneration. Traditional drug treatments have certain limitations, such as difficulty in penetrating the blood-nerve barrier and lack of pleiotropic effects. Therefore, there is an urgent need to build multifunctional nerve grafts that can effectively regulate the regenerative microenvironment and promote nerve regeneration. Nitric oxide (NO), a highly effective gas transmitter with diatomic radicals, is an important regulator of axonal growth and migration, synaptic plasticity, proliferation of neural precursor cells, and neuronal survival. Moreover, NO provides potential anti-inflammation, anti-oxidation, and blood vessel promotion applications. However, excess NO may cause cell death and neuroinflammatory cell damage. The prerequisite for NO treatment of peripheral nerve injury is that it is gradually released over time. In this study, we constructed an injectable NO slow-release system with two main components, including macromolecular NO donor nanoparticles (mPEG-P(MSNO-EG) nanoparticles, NO-NPs) and a carrier for the nanoparticles, mPEG-PA-PP injectable temperature-sensitive hydrogel. Due to the multiple physiological regulation of NO and better physiological barrier penetration, the conduit effectively regulates the inflammatory response and oxidative stress of damaged peripheral nerves, promotes nerve vascularization, and nerve regeneration and docking, accelerating the nerve regeneration process. STATEMENT OF SIGNIFICANCE: The slow regeneration speed of peripheral nerves is mainly due to the destruction of the regeneration microenvironment. Neural conduits with drug delivery capabilities have the potential to improve the microenvironment of nerve regeneration. However, traditional drugs are hindered by the blood nerve barrier and cannot effectively target the injured area. NO, an endogenous gas signaling molecule, can freely cross the blood nerve barrier and act on target cells. However, excessive NO can lead to cell apoptosis. In this study, a NO sustained-release system was constructed to regulate the microenvironment of nerve regeneration through various pathways and promote nerve regeneration.

Characterization of ovarian progenitor cells for their potential to generate steroidogenic theca cells in vitro.

In brief: Progenitor cells with ovulation-related tissue repair activity were identified with defined markers (LGR5, EPCR, LY6A, and PDGFRA), but their potentials to form steroidogenic cells were not known. This study shows that the cells can generate progenies with different steroidogenic activities. Abstract: Adult mammalian ovaries contain stem/progenitor cells necessary for folliculogenesis and ovulation-related tissue rupture repair. Theca cells are recruited and developed from progenitors during the folliculogenesis. Theca cell progenitors were not well defined. The aim of current study is to compare the potentials of four ovarian progenitors with defined markers (LY6A, EPCR, LGR5, and PDGFRA) to form steroidogenic theca cells in vitro. The location of the progenitors with defined makers was determined by immunohistochemistry and immunofluorescence staining of ovarian sections of adult mice. Different progenitor populations were purified by magnetic-activated cell sorting (MACS) and/or fluorescence-activated cell sorting (FACS) techniques from ovarian cell preparation and were tested for their abilities to generate steroidogenic theca cells in vitro. The cells were differentiated with a medium containing LH, ITS, and DHH agonist for 12 days. The results showed that EPCR+ and LGR5+ cells primarily distributed along the ovarian surface epithelium (OSE), while LY6A+ cells distributed in both the OSE and parenchyma. However, PDGFRA+ cells were exclusively located in interstitial compartment. When the progenitors were purified by these markers and differentiated in vitro, LY6A+ and PDGFRA+ cells formed steroidogenic cells expressing both CYP11A1 and CYP17A1 and primarily producing androgens, showing characteristics of theca-like cells, while LGR5+ cells generated steroidogenic cells devoid of CYP17A1 expression and androgen production, showing a characteristic of progesterone-producing cells (granulosa- or lutea-like cells). In conclusion, progenitors from both OSE and parenchyma of adult mice are capable of generating steroidogenic cells with different steroidogenic capacities, showing a possible lineage preference.

Curcuminoid PBPD induces cuproptosis and endoplasmic reticulum stress in cervical cancer via the Notch1/RBP-J/NRF2/FDX1 pathway.

Curcumin has been shown to have antitumor properties, but its low potency and bioavailability has limited its clinical application. We designed a novel curcuminoid, [1-propyl-3,5-bis(2-bromobenzylidene)-4-piperidinone] (PBPD), which has higher antitumor strength and improves bioavailability. Cell counting kit-8 was used to detect cell activity. Transwell assay was used to detect cell invasion and migration ability. Western blot and quantitative polymerase chain reaction were used to detect protein levels and their messenger RNA expression. Immunofluorescence was used to detect the protein location. PBPD significantly inhibited the proliferation of cervical cancer cells, with an IC50 value of 4.16 µM for Hela cells and 3.78 µM for SiHa cells, leading to the induction of cuproptosis. Transcriptome sequencing analysis revealed that PBPD significantly inhibited the Notch1/Recombination Signal Binding Protein for Immunoglobulin kappa J Region (RBP-J) and nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathways while upregulating ferredoxin 1 (FDX1) expression. Knockdown of Notch1 or RBP-J significantly inhibited NRF2 expression and upregulated FDX1 expression, leading to the inhibition of nicotinamide adenine dinucleotide phosphate activity and the induction of oxidative stress, which in turn activated endoplasmic reticulum stress and induced cell death. The overexpression of Notch1 or RBP-J resulted in the enrichment of RBP-J within the NRF2 promoter region, thereby stimulating NRF2 transcription. NRF2 knockdown resulted in increase in FDX1 expression, leading to cuproptosis. In addition, PBPD inhibited the acidification of tumor niche and reduced cell metabolism to inhibit cervical cancer cell invasion and migration. In conclusion, PBPD significantly inhibits the proliferation, invasion, and migration of cervical cancer cells and may be a novel potential drug candidate for treatment of cervical cancer.

Structure-activity relationship and mechanistic study of organotins as inhibitors of human, pig, and rat gonadal 3ß-hydroxysteroid dehydrogenases.

Organotins have been widely used in various industrial applications. This study investigated the structure-activity relationship as inhibitors of human, pig, and rat gonadal 3ß-hydroxysteroid dehydrogenases (3ß-HSD). Human KGN cell, pig, and rat testis microsomes were utilized to assess the inhibitory effects of 18 organotins on the conversion of pregnenolone to progesterone. Among them, diphenyltin, triethyltin, and triphenyltin exhibited significant inhibitory activity against human 3ß-HSD2 with IC50 values of 114.79, 106.98, and 5.40 µM, respectively. For pig 3ß-HSD, dipropyltin, diphenyltin, triethyltin, tributyltin, and triphenyltin demonstrated inhibitory effects with IC50 values of 172.00, 100.19, 87.00, 5.75, and 1.65 µM, respectively. Similarly, for rat 3ß-HSD1, dipropyltin, diphenyltin, triethyltin, tributyltin, and triphenyltin displayed inhibitory activity with IC50 values of 81.35, 43.56, 55.55, 4.09, and 0.035 µM, respectively. They were mixed inhibitors of pig and rat 3ß-HSD, while triphenyltin was identified as a competitive inhibitor of human 3ß-HSD2. The mechanism underlying the inhibition of organotins on 3ß-HSD was explored, revealing that they may disrupt the enzyme activity by binding to cysteine residues in the catalytic sites. This proposition was supported by the observation that the addition of dithiothreitol reversed the inhibition caused by all organotins except for triethyltin, which was partially reversed. In conclusion, this study provides valuable insights into the structure-activity relationship of organotins as inhibitors of human, pig, and rat gonadal 3ß-HSD. The mechanistic investigation suggests that these compounds likely exert their inhibitory effects through binding to cysteine residues in the catalytic sites.

Targeting osteopontin alleviates endometriosis and inflammation by inhibiting the RhoA/ROS axis and achieves non-invasive in vitro detection via menstrual blood.

STUDY QUESTION: How does osteopontin (OPN) in endometriosis ectopic stromal cells (EESCs) participate in the pathogenesis of endometriosis and achieve non-invasive detection in vitro? SUMMARY ANSWER: Targeted OPN regulates endometriosis's necroptosis and inflammatory state by inhibiting the RhoA/reactive oxygen species (ROS) axis, thereby alleviating endometriosis and enabling non-invasive detection of menstrual blood in vitro. WHAT IS KNOWN ALREADY: Endometriosis is a chronic inflammatory disease. Recent studies have shown that OPN plays an important role in disease progression by regulating cell death and inflammation. STUDY DESIGN, SIZE, DURATION: The study included 20 patients diagnosed with endometriosis (confirmed by laparoscopy and histology) and 10 controls without endometriosis. Endometriotic stromal cells were isolated from endometrial samples, while menstrual blood endometrial cells (MESCs) were isolated from menstrual blood. These cells were then cultured in vitro and utilized in subsequent experiments. PARTICIPANTS/MATERIALS, SETTING, METHODS: OPN expression in EESCs was assessed using inflammatory factor sequencing, immunohistochemical staining (IHC), quantitative real-time PCR (qRT-PCR) analysis, and Western blotting (WB). The biological behavior of OPN and its effects on inflammatory factors were examined using EdU, wound-healing, Transwell, and ELISA assays. Necroptosis in EESCs and its impact on inflammatory factors were detected through qRT-PCR, WB, and Calcein-AM/PI fluorescence assays. The examination of mitochondrial stress in EESCs involved the use of the Mitochondrial Membrane Potential (ΔΨm) Assay, ROS detection, and Calcein-AM Loading/cobalt chloride Quenching. qRT-PCR, WB, and other experiments were conducted to verify the regulation of necroptosis and inflammatory factor levels in EESCs by OPN through the RhoA/ROS axis. Knockdown of OPN and its inhibitory effect on endometriosis lesion size were confirmed using AAV9 virus, IHC, qRT-PCR, WB, and other experiments. Additionally, OPN expression in MESCs was detected using transcriptome sequencing, RT-PCR, WB, and other experiments. MAIN RESULTS AND THE ROLE OF CHANCE: In vitro assays demonstrated a significant upregulation of OPN in EESCs, and the knockdown of OPN effectively inhibited necroptosis and the release of inflammatory factors. OPN inhibited necroptosis and inflammatory factor release by mediating RhoA-dependent ROS production and blocking mixed lineage kinase domain-like protein phosphorylation at the cell membrane. In vivo, targeting of OPN can inhibit the growth of endometriosis lesions. Clinically, OPN was also significantly upregulated in the menstrual blood of patients with endometriosis. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Due to limitations in obtaining surgical specimens, our study primarily involved collecting endometriosis tissues from women during the proliferative and secretory phases of the menstrual cycle. We observed a significant overexpression of OPN in the samples used for our investigation. However, the expression of OPN in endometriosis tissues during the intermenstrual phase remains unknown. WIDER IMPLICATIONS OF THE FINDINGS: Our findings highlight the pivotal role of the OPN/RhoA/ROS axis in the regulation of necroptosis and the release of inflammatory factors. OPN knockdown exerts a therapeutic effect in vivo, and the high expression detection of OPN in menstrual blood in vitro. In summary, targeting OPN provides possibilities for the treatment and detection of endometriosis. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Natural Science Foundation of China (82071626), the Zhejiang Province Public Welfare Technology Application Research Project (LGF21H040010), and the Clinical Research project of the Second Affiliated Hospital of Wenzhou Medical University (1010293). The authors have no conflicts of interest.

Effects of non-landslide sampling strategies on machine learning models in landslide susceptibility mapping.

This study aims to explore the effects of different non-landslide sampling strategies on machine learning models in landslide susceptibility mapping. Non-landslide samples are inherently uncertain, and the selection of non-landslide samples may suffer from issues such as noisy or insufficient regional representations, which can affect the accuracy of the results. In this study, a positive-unlabeled (PU) bagging semi-supervised learning method was introduced for non-landslide sample selection. In addition, buffer control sampling (BCS) and K-means (KM) clustering were applied for comparative analysis. Based on landslide data from Qiaojia County, Yunnan Province, China, collected in 2014, three machine learning models, namely, random forest, support vector machine, and CatBoost, were used for landslide susceptibility mapping. The results show that the quality of samples selected using different non-landslide sampling strategies varies significantly. Overall, the quality of non-landslide samples selected using the PU bagging method is superior, and this method performs best when combined with CatBoost for predicting (AUC = 0.897) landslides in very high and high susceptibility zones (82.14%). Additionally, the KM results indicated overfitting, displaying high accuracy for validation but poor statistical outcomes for zoning. The BCS results were the worst.

Microfluidics-derived hierarchical microparticles for the delivery of dienogest for localized endometriosis therapy.

Drug therapy is one of the most important strategies for treating gynecological diseases. Local drug delivery is promising for achieving optimal regional drug exposure, considering the complex anatomy and dynamic environment of the upper genital tract. Here, we present microparticle-based microcarriers with a hierarchical structure for localized dienogest (DNG) delivery and endometriosis treatment. The microparticles were fabricated by microfluidics and consisted of photo-crosslinked bovine serum albumin hydrogel particles (D@P-B MPs) encapsulating DNG-loaded PLGA (poly lactic-co-glycolic acid) microspheres. Such design enables the microparticles to have sustained release capacity and cell adhesion ability. Based on this, the microparticles were applied for the treatment of peritoneal endometriosis through intraperitoneal injection. The performance of the microparticles in inhibiting the growth of ectopic lesions as well as their anti-inflammatory, anti-angiogenesis, and pelvic pain-relieving effects are well demonstrated in vivo. These findings indicate that the present hierarchical microparticles are good candidates for localized treatment of endometriosis and are promising for the management of gynecological diseases. STATEMENT OF SIGNIFICANCE: We prepared photo-crosslinked bovine serum albumin hydrogel particles (D@P-B MPs) encapsulating DNG-loaded PLGA microspheres using microfluidic electrospray. Such hierarchical structure provided multiple functions of the particles as drug carriers. The hierarchical microparticles not only supported the sustained release of drugs but also provided adhesion to human ectopic endometrial stromal cells. The hierarchical microparticles represented a localized treatment method for endometriosis and is promising for the management of gynecological diseases.

First-line treatment of driver gene-negative metastatic lung adenocarcinoma with malignant pleural effusion: Should chemotherapy be combined with an immune checkpoint inhibitor or bevacizumab?

Patients with metastatic lung adenocarcinoma (MLA) and malignant pleural effusion (MPE) without driver gene mutations have a poor prognosis. None of the standard treatment strategies is recommended for such patients. We retrospectively analyzed the efficacy of the first-line treatment for this specific population: standard platinum-based doublet chemotherapy (CT), CT plus an immune checkpoint inhibitor (CT plus ICI), and CT plus bevacizumab (CT plus Bev). A total of 323 eligible patients were enrolled: CT alone (n = 166), CT plus Bev (n = 72), and CT plus ICI (n = 85). Treatment efficacy assessments were performed every two cycles according to the RECIST guidelines. The endpoints were overall survival (OS) and progression-free survival (PFS). Kaplan-Meier (K‒M) curves and the log-rank test were used to compare OS and PFS. p < 0.05 was the threshold of significance (statistical software: SPSS). The median follow-up was 11.4 months (range, 2.1-49.6 months). PFS and OS in the CT plus ICI/CT plus Bev cohort were significantly longer than those in the CT group (PFS: 7.8/6.4/3.9 months, p < 0.0001; OS: 16.4/15.6/9.6 months, p < 0.0001, respectively). CT plus Bev had better PFS and OS than CT plus ICI/CT in PD-L1 < 1% patients (PFS: 8.4/5.0/3.8 months, p < 0.0001; OS: 15.6/12.9/9.3 months, p < 0.0001). Among patients with PD-L1 1-49%, CT plus ICI led to a longer PFS and OS (PFS: 8.9/5.8/4.2 months, p = 0.009; OS: 24.2/18.8/11.5 months, p = 0.03). In the cohort with PD-L1 ≥ 50%, CT plus ICI was still the best first-line treatment (PFS: 19.7/13.8/9.6 months, p = 0.033; OS: 27.2/19.6/14.9 months, p = 0.047). In driver gene-negative MLA with MPE, CT plus Bev or ICI better controlled MPE and significantly prolonged survival compared to CT alone. PD-L1 expression (negative/positive) may be a key factor influencing the choice of CT plus Bev or ICI.

Study on the space field reconstruction method of the radial basis function of electromagnetic radiation under optimal parameters.

Electromagnetic radiation (EM) pollution has a certain impact on human life and health, and the reconstruction of the EM space field in this paper is of great practical significance for EM analysis and research. The radial basis function (RBF) sufficiently considers the influence of each sampling point and is more suitable for reconstructing the EM space field than other spatial interpolation methods. Currently, when RBF is used to reconstruct the EM space field, the optimal determination of the basis function and shape parameter (SP) is rarely considered. This ultimately leads to low reconstruction accuracy of the EM space field. Therefore, in this paper, the particle swarm optimization (PSO) is used to calculate the optimal SP of the RBF. On this basis, reliable EM space field reconstruction is performed, which helps people understand the EM distribution characteristics in actual situations from a visual perspective. The EM sampling data of a region on the Yunnan Normal University campus are used as the data source, and the RBF under the optimal parameters is used for EM reconstruction. The accuracy of its interpolation results is evaluated and compared and analyzed with inverse distance weighting (IDW) after distance index optimization. The results show that the RBF under optimal parameters reconstructs the EM space field with high accuracy and good effect, which can truly reflect the actual distribution of EM.

Electromagnetic radiation (EM) pollution has a great impact on the surrounding environment. Therefore, EM space field reconstruction can help us analyze the characteristics of the electromagnetic environment in a visual way. Radial Basis Function (RBF) is a method more suitable for EM space field reconstruction than other methods because it fully considers the influence of each sampling point. However, when currently using RBF to reconstruct the EM space field, few researchers consider how to choose the most appropriate basis function and shape parameter (SP). This results in low reconstruction accuracy. Therefore, this study uses particle swarm optimization (PSO) to find the optimal SP parameters for reliable EM space field reconstruction. The study used the EM sampling data of an area within the campus of Yunnan Normal University as the study material, and a parameter-optimized RBF method was adopted for the reconstruction of the EM space field. The reconstruction results were then evaluated for accuracy and compared and analyzed with the IDW method optimized with a distance index. Research results show that using RBF with optimal parameters to reconstruct the EM space field has high accuracy and can effectively reflect the actual EM distribution, thereby helping people better understand the characteristics of the electromagnetic environment.

Designing Bioorthogonal Reactions for Biomedical Applications.

Bioorthogonal reactions are a class of chemical reactions that can be carried out in living organisms without interfering with other reactions, possessing high yield, high selectivity, and high efficiency. Since the first proposal of the conception by Professor Carolyn Bertozzi in 2003, bioorthogonal chemistry has attracted great attention and has been quickly developed. As an important chemical biology tool, bioorthogonal reactions have been applied broadly in biomedicine, including bio-labeling, nucleic acid functionalization, drug discovery, drug activation, synthesis of antibody-drug conjugates, and proteolysis-targeting chimeras. Given this, we summarized the basic knowledge, development history, research status, and prospects of bioorthogonal reactions and their biomedical applications. The main purpose of this paper is to furnish an overview of the intriguing bioorthogonal reactions in a variety of biomedical applications and to provide guidance for the design of novel reactions to enrich bioorthogonal chemistry toolkits.

An injectable and adaptable hydrogen sulfide delivery system for modulating neuroregenerative microenvironment.

Peripheral nerve regeneration is a complex physiological process. Single-function nerve scaffolds often struggle to quickly adapt to the imbalanced regenerative microenvironment, leading to slow nerve regeneration and limited functional recovery. In this study, we demonstrate a "pleiotropic gas transmitter" strategy based on endogenous reactive oxygen species (ROS), which trigger the on-demand H2S release at the defect area for transected peripheral nerve injury (PNI) repair through concurrent neuroregeneration and neuroprotection processing. This H2S delivery system consists of an H2S donor (peroxyTCM) encapsulated in a ROS-responsive polymer (mPEG-PMet) and loaded into a temperature-sensitive poly (amino acid) hydrogel (mPEG-PA-PP). This multi-effect combination strategy greatly promotes the regeneration of PNI, attributed to the physiological effects of H2S. These effects include the inhibition of inflammation and oxidative stress, protection of nerve cells, promotion of angiogenesis, and the restoration of normal mitochondrial function. The adaptive release of pleiotropic messengers to modulate the tissue regeneration microenvironment offers promising peripheral nerve repair and tissue engineering opportunities.

Transcriptomic characterization of interactions between sodium selenite and coenzyme Q10 on preventing cadmium-induced testicular defects.

The effect of heavy metal cadmium (Cd) on testicular function is recognized. However, the mechanism involved is not well-established. In the present study, we analyzed the testicular transcriptomic changes induced by acute Cd exposure of adult rats with and without supplementation of antioxidants selenium (Se) and/or coenzyme Q10 (CoQ). Cd significantly decreased serum testosterone and two steroidogenic proteins SCARB1 and STAR. RNA-Seq analyses of testicular RNAs revealed specific activation of oxidative stress-, inflammation-, MAPK- and NF-κB-related signaling molecules. In addition, Cd treatment down-regulated gene for I, III and IV complexes of mitochondrial electron transport chain and up-regulated genes for NADPH-oxidase, major cascade in ROS production. The decrease in steroidogenesis and increase in inflammation may result from oxidative stress since supplementation of Se and CoQ, but not with either alone, almost completely prevented these changes, including overall alterations in transcriptome. Cd exposure induced total of 1192 differentially expressed genes (DEGs), which was reduced to 29 without considering confounding factors associated with Se/CoQ, a 97.6% protection rate. In conclusion, Cd exposure inhibited Leydig cell steroidogenesis by down-regulating SCARB1 and STAR through increasing oxidative stress and inflammation, but Se plus CoQ synergistically prevented all the changes induced by the Cd exposure.

Microstructure and Efflorescence Resistance of Metakaolin Geopolymer Modified by 5A Zeolite.

In order to reduce the degree of efflorescence in alkali-activated metakaolin geopolymers, a modified 5A zeolite with cation-exchange properties was used to reduce the content of free alkali metal cations in the geopolymer. This work aims to investigate the effect of different dosages of modified 5A zeolite on the microstructure and properties of geopolymer by using compressive strength testing, pore structure analysis (BET), and SEM-EDS. The cation content in the leachate was evaluated using inductively coupled plasma atomic emission spectrometry (ICP-OES). The efflorescence area of the geopolymer was calculated using Image Pro Plus (IPP) software to evaluate the effect of modified 5A zeolite on the degree of efflorescence of the geopolymer and to reveal the effect of modified 5A zeolite on the migration patterns of Na+ and Ca2+ in the geopolymer. The results showed that modified 5A zeolite with a 4 wt.% content could optimize the pore structure and enhance the mechanical properties of MK geopolymer through internal curing and micro-aggregate effects, which could also exchange cations with the pore solution to form (N, C)-A-S-H gels. The Na+ leaching was reduced by 19.4%, and the efflorescence area of the MK geopolymer was reduced by 57.3%.

Exploring a Linear Combination Feature for Predicting the Conductance of Parallel Molecular Circuits.

An accurate rule for predicting conductance is the cornerstone of developing molecular circuits and provides a promising solution for miniaturizing electric circuits. The successful prediction of series molecular circuits has proven the possibility of establishing a rule for molecular circuits under quantum mechanics. However, the quantitatively accurate prediction has not been validated by experiments for parallel molecular circuits. Here we used 1,3-dihydrobenzothiophene (DBT) to build the parallel molecular circuits. The theoretical simulation and single-molecule conductance measurements demonstrated that the conductance of the molecule containing one DBT is the unprecedented linear combination of the conductance of the two individual channels with respective contribution weights of 0.37 and 0.63. With these weights, the conductance of the molecule containing two DBTs is predicted as 1.81 nS, matching perfectly with the measured conductance (1.82 nS). This feature offers a potential rule for quantitatively predicting the conductance of parallel molecular circuits.

WTAP gene variants and susceptibility to ovarian endometriosis in a Chinese population.

Background: Endometriosis is a common chronic gynecologic disorder with a significant negative impact on women's health. Wilms tumor 1-associated protein (WTAP) is a vital component of the RNA methyltransferase complex for N6-methyladenosine modification and plays a critical role in various human diseases. However, whether single nucleotide polymorphisms (SNPs) of the WTAP gene predispose to endometriosis risk remains to be investigated. Methods: We genotyped three WTAP polymorphisms in 473 ovarian endometriosis patients and 459 control participants using the Agena Bioscience MassArray iPLEX platform. The logistic regression models were utilized to assess the associations between WTAP SNPs and the risk of ovarian endometriosis. Results: In the single-locus analyses, we found that the rs1853259 G variant genotypes significantly increased, while the rs7766006 T variant genotypes significantly decreased the association with ovarian endometriosis risk. Combined analysis indicated that individuals with two unfavorable genotypes showed significantly higher ovarian endometriosis risk (adjusted OR = 1.71 [1.23-2.37], p = 0.001) than those with zero risk genotypes. In the stratified analysis, the risk effect of the rs1853259 AG/GG and rs7766006 GG genotypes was evident in subgroups of age ≤30, gravidity≤1, parity≤1, rASRM stage I, and the rs7766006 GG genotype was associated with worse risk (adjusted OR = 1.64 [1.08-2.48], p = 0.021) in the patients with rASRM stage II + III + IV. The haplotype analysis indicated that individuals with GGG haplotypes had a higher risk of ovarian endometriosis than wild-type AGG haplotype carriers. Moreover, false positive report probability and Bayesian false discovery probability analysis validated the reliability of the significant results. The quantitative expression trait loci analysis revealed that rs1853259 and rs7766006 were correlated with the expression levels of WTAP. Conclusion: Our findings demonstrated that WTAP polymorphisms were associated with susceptibility to ovarian endometriosis among Chinese women.

Study on landslide susceptibility mapping with different factor screening methods and random forest models.

The number of input factors affects the prediction accuracy of a model. Factor screening plays an important role as the starting point for data input. The aim of this study is to explore the influence of different factor screening methods on the prediction results. Taking the 2014 landslide inventory of Jingdong County as an example, a landslide database was constructed based on 136 landslide events and 11 selected factors, which were randomly divided into a training dataset and a test dataset according to a ratio of 7:3. Four factor screening methods, namely, the information gain ratio (IGR), GeoDetector, Pearson correlation coefficient and multicollinearity test (MT), were selected to screen the factors. A random forest (RF) model was then used in combination with each factor set for landslide susceptibility mapping (LSM). Finally, accuracy validation was performed using confusion matrices and ROC curves. The results show that factor screening is beneficial in improving the accuracy of the resulting model compared to the original model. Second, the IGR_RF model had the highest AUC value (0.9334), which was higher than that of the MT_RF model without factor screening (0.9194), and the IGR_RF model predicted the most landslides in the very high susceptibility zone (51.22%), indicating the good prediction performance of the IGR_RF model. Finally, the factor weighting analysis revealed that NDVI, elevation and aspect had the greatest influence on landslides in Jingdong County and that curvature had the least influence on landslides. This study can provide a reference for factor screening in LSM.