Aflibercept Loaded Eye-Drop Hydrogel Mediated with Cell-Penetrating Peptide for Corneal Neovascularization Treatment.

Corneal neovascularization (CoNV) is a major cause of visual impairment worldwide. Currently, available treatment options have limited efficacy and are associated with adverse effects due to biological barriers and clearance mechanisms. To address this challenge, a novel topical delivery system is developed-Gel 2_1&Eylea-an aflibercept-loaded eye-drop hydrogel mediated with cell-penetrating peptide 1. Gel 2_1&Eylea demonstrates superior membrane permeability, increased stability, and prolonged drug retention time on the ocular surface, and thus may improve drug efficacy. In a rabbit CoNV model, Gel 2_1&Eylea significantly reduces the density of neovascularization with no adverse effects on normal corneoscleral limbal vessels, demonstrating high efficacy and biocompatibility. This work identifies a promising treatment for CoNV which has the potential to benefit other ocular neovascular diseases.

Melatonin: Unveiling the functions and implications in ocular health.

Melatonin, a versatile hormone produced by the pineal gland, has garnered considerable scientific interest due to its diverse functions. In the eye, melatonin regulates a variety of key processes like inhibiting angiogenesis by reducing vascular endothelial growth factor levels and protecting the blood-retinal barrier (BRB) integrity by enhancing tight junction proteins and pericyte coverage. Melatonin also maintains cell health by modulating autophagy via the Sirt1/mTOR pathways, reduces inflammation, promotes antioxidant enzyme activity, and regulates intraocular pressure fluctuations. Additionally, melatonin protects retinal ganglion cells by modulating aging and inflammatory pathways. Understanding melatonin's multifaceted functions in ocular health could expand the knowledge of ocular pathogenesis, and shed new light on therapeutic approaches in ocular diseases. In this review, we summarize the current evidence of ocular functions and therapeutic potential of melatonin and describe its roles in angiogenesis, BRB integrity maintenance, and modulation of various eye diseases, which leads to a conclusion that melatonin holds promising treatment potential for a wide range of ocular health conditions.

DNA barcoding of the genus Gampsocleis (Orthoptera, Tettigoniidae) from China.

DNA barcoding is a useful addition to the traditional morphology-based taxonomy. A ca. 650 bp fragment of the 5' end of mitochondrial cytochrome c oxidase subunit I (hereafter COI-5P) DNA barcoding was sued as a practical tool for Gampsocleis species identification. DNA barcodes from 889 specimens belonging to 8 putative Gampsocleis species was analyzed, including 687 newly generated DNA barcodes. These barcode sequences were clustered/grouped into Operational Taxonomic Units (OTUs) using the criteria of five algorithms, namely Barcode Index Number (BIN) System, Assemble Species by Automatic Partitioning (ASAP), a Java program uses an explicit, determinate algorithm to define Molecular Operational Taxonomic Unit (jMOTU), Generalized Mixed Yule Coalescent (GMYC), and Bayesian implementation of the Poisson Tree Processes model (bPTP). The Taxon ID Tree grouped sequences of morphospecies and almost all MOTUs in distinct nonoverlapping clusters. Both long- and short-winged Gampsocleis species are reciprocally monophyletic in the Taxon ID Tree. In BOLD, 889 barcode sequences are assigned to 17 BINs. The algorithms ASAP, jMOTU, bPTP and GMYC clustered the barcode sequences into 6, 13, 10, and 23 MOTUs, respectively. BIN, ASAP, and bPTP algorithm placed three long-winged species, G. sedakovii, G. sinensis and G. ussuriensis within the same MOTU. All species delimitation algorithms split two short-winged species,G. fletcheri and G. gratiosa into at least two MOTUs each, except for ASAP algorithm. More detailed molecular and morphological integrative studies are required to clarify the status of these MOTUs in the future.

Response of petroleum-contaminated soil to chemical oxidation combined with biostimulation.

In this study, a microcosm experiment was conducted to investigate the effects of Na2S2O8 preoxidation combined with biostimulation on petroleum-contaminated soil remediation. The response of microbial community during this process was explored using BIOLOG ECO microplate carbon utilization method and 16 s rDNA high-throughput sequencing. The results showed that use of 10 mg/g Na2S2O8 removed 19.8 % of the petroleum hydrocarbons, reduced soil biotoxicity and did not affect soil microbial activity compared to other concentrations. Therefore, sodium persulfate of ca. 10 mg/g was used to oxidize petroleum in soil before the biostimulation experiment with organic and inorganic fertilizers. Our finding showed that the content of total petroleum hydrocarbons (TPHs) in soil was reduced by 43.3 % in inorganic fertilizer treatment after 60 days. The results of BIOLOG ECO microplate carbon utilization analysis and 16 S rDNA high-throughput sequencing further confirmed that biostimulation quickly restored the microbial activities in oxidant treated soil. The main marker bacteria in chemical oxidation combined with biostimulation remediation were Arthrobacter and Paenarthrobacter, and their relative abundances were both significantly negatively correlated with the content of petroleum hydrocarbons in soil.

Identification and clinical significance of tsRNAs and miRNAs in PBMCs of treatment-requiring retinopathy of prematurity.

The aim of the study is to reveal the expression profiling and clinical significance of peripheral blood mononuclear cell (PBMC) tRNA-derived small RNAs (tsRNAs) and microRNAs (miRNAs) of premature infants with treatment-requiring retinopathy of prematurity (ROP). Significantly altered tsRNAs and miRNAs were screened using small RNA sequencing. RT-qPCR was used to verify the altered RNAs identified by small RNA transcriptomics. The target genes, their enriched functions, and possibly involved signaling pathways were identified by bioinformatics analyses. According to the small RNA sequencing, 125 tsRNAs and 205 miRNAs were significantly altered in PBMCs obtained from infants with treatment-requiring ROP compared with the premature controls without retinopathy. We preliminarily validated the significant alterations of 6 tsRNAs and 9 miRNAs. The target genes for those tsRNAs were enriched for cellular macromolecule metabolic process, intracellular anatomical structure, transcription regulatory region nucleic acid binding, and Th17 cell differentiation; those of the altered miRNAs were enriched for the developmental process, cell junction, DNA-binding transcription activator activity, and FoxO signaling pathway. By verification with the extended sample size, we identified tsRNAs and miRNAs that could be potential biomarkers with clinical values. The study recognized the alterations and clinical significance of changed tsRNA/miRNA profiles in PBMCs from premature infants with ROP. These significantly altered tsRNAs and miRNAs might be useful as potential diagnostic biomarkers and molecular targets for treatment-requiring ROP.

m6A modifications of circular RNAs in ischemia-induced retinal neovascularization.

Ischemia-induced pathological neovascularization in the retina is a leading cause of blindness in various age groups. The purpose of the current study was to identify the involvement of circular RNAs (circRNAs) methylated by N6-methyladenosine (m6A), and predict their potential roles in oxygen-induced retinopathy (OIR) in mice. Methylation assessment via microarray analysis indicated that 88 circRNAs were differentially modified by m6A methylation, including 56 hyper-methylated circRNAs and 32 hypo-methylated circRNAs. Gene ontology enrichment analysis predicted that the enriched host genes of the hyper-methylated circRNAs were involved in cellular process, cellular anatomical entity, and protein binding. Host genes of the hypo-methylated circRNAs were enriched in the regulation of cellular biosynthetic process, the nucleus, and binding. According to the Kyoto Encyclopedia of Genes and Genomes analysis, those host genes were involved in the pathways of selenocompound metabolism, salivary secretion, and lysine degradation. MeRIP-qPCR verified significant alterations in m6A methylation levels of mmu_circRNA_33363, mmu_circRNA_002816, and mmu_circRNA_009692. In conclusion, the study revealed the m6A modification alterations in OIR retinas, and the findings above shed light on the potential roles of m6A methylation in circRNA regulatory functions in the pathogenesis of ischemia-induced pathological retinal neovascularization.

Stratifin promotes renal dysfunction in ischemic and nephrotoxic AKI mouse models via enhancing RIPK3-mediated necroptosis.

Stratifin (SFN) is a member of the 14-3-3 family of highly conserved soluble acidic proteins, which regulates a variety of cellular activities such as cell cycle, cell growth and development, cell survival and death, and gene transcription. Acute kidney injury (AKI) is prevalent disorder characterized by inflammatory response, oxidative stress, and programmed cell death in renal tubular epithelial cells, but there is still a lack of effective therapeutic target for AKI. In this study, we investigated the role of SFN in AKI and the underlying mechanisms. We established ischemic and nephrotoxic AKI mouse models caused by ischemia-reperfusion (I/R) and cisplatin, respectively. We conducted proteomic and immunohistochemical analyses and found that SFN expression levels were significantly increased in AKI patients, cisplatin- or I/R-induced AKI mice. In cisplatin- or hypoxia/reoxygenation (H/R)-treated human proximal tubule epithelial cells (HK2), we showed that knockdown of SFN significantly reduced the expression of kidney injury marker Kim-1, attenuated programmed cell death and inflammatory response. Knockdown of SFN also significantly alleviated the decline of renal function and histological damage in cisplatin-caused AKI mice in vivo. We further revealed that SFN bound to RIPK3, a key signaling modulator in necroptosis, to induce necroptosis and the subsequent inflammation in cisplatin- or H/R-treated HK2 cells. Overexpression of SFN increased Kim-1 protein levels in cisplatin-treated MTEC cells, which was suppressed by RIPK3 knockout. Taken together, our results demonstrate that SFN that enhances cisplatin- or I/R-caused programmed cell death and inflammation via interacting with RIPK3 may serve as a promising therapeutic target for AKI treatment.

Organic Sulfonium-Stabilized High-Efficiency Cesium or Methylammonium Lead Bromide Perovskite Nanocrystals.

Herein, we report a new X-type ligand, i.e., organic sulfonium bromide, for high-efficiency CsPbBr3 and MAPbBr3 (MA=methylammonium) perovskite nanocrystals (PNCs). We first confirmed the facile synthesis of the titled ligands in N,N-dimethylformamide at room temperature. By reacting dodecylmethylsulfide with allyl bromide, (3-bromopropyl)trimethoxysilane, and 1,4-dibromobutane, respectively, three representative ligands (named DAM, DSM, and DMM) are acquired. All of them result in CsPbBr3 and MAPbBr3 PNCs with near-unity photoluminescence quantum yield (PLQY) and decent ambient stability (no less than 90 % PLQY after 2 months) using a room-temperature ligand-assisted reprecipitation technique. Among them, DSM and DMM endow CsPbBr3 PNCs with higher thermal/light stability arising from the cross-linkable or bidentate ligand structure. Further, DSM-CsPbBr3 PNCs can be incorporated into polystyrene through in situ thermal polymerization and the composite shows a record-high PLQY of 93.8 %.

Ginkgo biloba extracts inhibit post-ischemic LTP through attenuating EPSCs in rat hippocampus.

Ginkgo biloba extract 761 (EGb761), a standardized extract from the Ginkgo biloba leaf, is purported to inhibit NMDA receptor-mediated neuronal excitotoxicity and protect neurons form ischemic injury. However, the specific signal pathway involved in the effects of EGb761 on synaptic plasticity is still in dispute. In this article, effects of EGb761 and its monomer component ginkgolide A (GA), ginkgolide B (GB), ginkgolide C (GC) and quercetin on rat hippocampal synaptic plasticity were studied. The evoked Excitatory postsynaptic currents (EPSCs) and miniature EPSCs were recorded on hippocampal slices from SD rats (14-21 days of age) by whole-cell patch-clamp recording and long-term potentiation (LTP) was induced by theta-burst stimulation. Acutely applied EGb761 inhibited the LTP, but bilaterally affect the evoked EPSCs. The evoked EPSCs were increased by incubation of lower concentration of EGb761, then the evoked EPSCs were decreased by incubation of higher concentration of EGb761. EGb761 monomer component GA, GB and GC could also inhibit the TBS-induced LTP and EPSC amplitude but not paired-pulse ratio (PPR). But quercetin, another monomer component of EGb761, led to increase in EPSC amplitude and decrease in PPR. Simultaneously, EGb761 and its monomer component ginkgolides inhibited the post-ischemic LTP (i-LTP) by inhibiting the EPSCs and the AMPA receptor subunit GluA1 expression on postsynaptic membrane. The results indicated that high concentration of EGb761 might inhibit LTP and i-LTP through inhibition effects of GA, GB and GC on AMPA receptors.

Highly Reversible Sodiation/Desodiation from a Carbon-Sandwiched SnS2 Nanosheet Anode for Sodium Ion Batteries.

The further improvement of sodium ion batteries requires the elucidation of the mechanisms pertaining to reversibility, which allows the novel design of the electrode structure. Here, through a hydrogel-embedding method, we are able to confine the growth of few-layer SnS2 nanosheets between a nitrogen- and sulfur-doped carbon nanotube (NS-CNT) and amorphous carbon. The obtained carbon-sandwiched SnS2 nanosheets demonstrate excellent sodium storage properties. In operando small-angle X-ray scattering combined with the ex situ X-ray absorption near edge spectra reveal that the redox reactions between SnS2/NS-CNT and the sodium ion are highly reversible. On the contrary, the nanostructure evolution is found to be irreversible, in which the SnS2 nanosheets collapse, followed by the regeneration of SnS2 nanoparticles. This work provides operando insights into the chemical environment evolution and structure change of SnS2-based anodes, elucidating its reversible reaction mechanism, and illustrates the significance of engineered carbon support in ensuring the electrode structure stability.

Aggregation-Induced Emission Gold Clustoluminogens for Enhanced Low-Dose X-ray-Induced Photodynamic Therapy.

The use of gold nanoparticles as radiosensitizers is an effective way to boost the killing efficacy of radiotherapy while drastically limiting the received dose and reducing the possible damage to normal tissues. Herein, we designed aggregation-induced emission gold clustoluminogens (AIE-Au) to achieve efficient low-dose X-ray-induced photodynamic therapy (X-PDT) with negligible side effects. The aggregates of glutathione-protected gold clusters (GCs) assembled through a cationic polymer enhanced the X-ray-excited luminescence by 5.2-fold. Under low-dose X-ray irradiation, AIE-Au strongly absorbed X-rays and efficiently generated hydroxyl radicals, which enhanced the radiotherapy effect. Additionally, X-ray-induced luminescence excited the conjugated photosensitizers, resulting in a PDT effect. The in vitro and in vivo experiments demonstrated that AIE-Au effectively triggered the generation of reactive oxygen species with an order-of-magnitude reduction in the X-ray dose, enabling highly effective cancer treatment.

RIPK1 inhibitor Cpd-71 attenuates renal dysfunction in cisplatin-treated mice via attenuating necroptosis, inflammation and oxidative stress.

Acute kidney injury (AKI) is a destructive clinical condition induced by multiple insults including ischemic reperfusion, nephrotoxic drugs and sepsis. It is characterized by a sudden decline in renal function, in addition to excessive inflammation, oxidative stress and programmed cell death of renal tubular epithelial cells. RIPK1-mediated necroptosis plays an important role in AKI. In the present study, we evaluated the treatment effects of Compound-71 (Cpd-71), a novel RIPK1 inhibitor, by comparing with Necrostatin-1 (Nec-1), a classic RIPK1 inhibitor, which has several drawbacks like the narrow structure-activity relationship (SAR) profile, moderate potency and non-ideal pharmacokinetic properties, in vivo and in vitro Our results showed that pretreatment of Cpd-71 attenuated cisplatin-induced renal injury, restored renal function and suppressed renal inflammation, oxidative stress and cell necroptosis. In addition, Cpd-71 inhibited renal damage while reducing the up-regulated serum creatinine (Cr) and blood urea nitrogen (BUN) levels in established AKI mice model. Consistently, we confirmed that Cpd-71 exhibited more effectively suppressive effect on cisplatin-induced renal tubular cell necroptosis than Nec-1, by physically binding to the allosteric type III ligand binding site of RIPK1, thereby reduced RIPK1 kinase activity, RIPK1/RIPK3 complex formation and phosphor-MLKL membrane translocation by molecular docking, Western blot, co-immunoprecipitation and cellular thermal shift assay (CETSA). Taken together, we currently showed that targeting RIPK1 with Cpd-71 may serve as a promising clinical candidate for AKI treatment.

[Antiendotoxin effect of Jinhuaqingre capsules].

Objective: To investigate the anti-pyretic and anti-endotoxin effect of Chinese herb medicine Jinhuaqingre capsules. Methods: Thirty healthy male New Zealand rabbits with lipopolysaccharide-induced fever were divided into 5 groups (6 rabbits in each): animals in model group were given normal saline by gavage, animals in positive control group were given aspirin (0.2 g/kg), and animals in Jinhuaqingre groups were given Jinhuaqingre capsules 6.0, 3.0 or 1.5 g/kg, respectively. The changes in body temperature of rabbits were observed. Fifty healthy Kunming mice were divided into 5 groups (10 mice in each): mice in model group were given normal saline by gavage, mice in positive control group were given aspirin (0.2 g/kg), and those in Jinhuaqingre groups were given Jinhuaqingre capsules 6.0, 3.0, 1.5 g/kg, respectively. Matrix coloration method was used to detect the degradation rate of endotoxin in mice. Results: The body temperature in rabbits of high and medium dose Jinhuaqingre capsule groups declined significantly 60 min after drug administration, and the temperature of high-dose group returned to the baseline after 300 min; while the body temperature of low-dose group started to decline at 180 min after drug administration. The endotoxin degradation rates in mice of high, medium and low dose groups was (56.73±3.12)%, (47.23±1.77)% and (21.08±2.30)% at 30 min after drug administration; those were (82.76±1.00)%, (64.75±1.77)% and (38.21±1.57)% at 60 min after drug administration, respectively. Conclusion: Chinese herb medicine Jinhuanigre capsules have anti-pyretic and anti-endotoxin effects, which may provide a new option for the treatment of heat-toxin syndrome.

The role of circadian clock in regulating cell functions: implications for diseases.

The circadian clock system orchestrates daily behavioral and physiological rhythms, facilitating adaptation to environmental and internal oscillations. Disruptions in circadian rhythms have been linked to increased susceptibility to various diseases and can exacerbate existing conditions. This review delves into the intricate regulation of diurnal gene expression and cell function by circadian clocks across diverse tissues. . Specifically, we explore the rhythmicity of gene expressions, behaviors, and functions in both immune and non-immune cells, elucidating the regulatory effects and mechanisms imposed by circadian clocks. A detailed discussion is centered on elucidating the complex functions of circadian clocks in regulating key cellular signaling pathways. We further review the circadian regulation in diverse diseases, with a focus on inflammatory diseases, cancers, and systemic diseases. By highlighting the intimate interplay between circadian clocks and diseases, especially through clock-controlled cell function, this review contributes to the development of novel disease intervention strategies. This enhanced understanding holds significant promise for the design of targeted therapies that can exploit the circadian regulation mechanisms for improved treatment efficacy.

Relationship between diagnosis of conus arteriosus malformation and genetic diagnosis results in fetal cardiac axis abnormalities by echocardiography during middle pregnancy.

Objective: To explore the clinical value of echocardiography in detecting fetal cardiac axis abnormalities during middle pregnancy for diagnosing conus arteriosus malformation, and to compare and analyze the genetic diagnosis results, in order to provide evidence for clinical diagnosis and intervention. Methods: Four hundred twenty-one fetuses with conus arteriosus malformation from January 2020 to October 2023 were included as the conus arteriosus malformation group, and 917 healthy fetuses (all single fetuses) matched at the same gestational age were selected as the healthy group. Results: There was no significant difference in gestational weeks between two groups (P > 0.05). The age of pregnant women in conus arteriosus malformation group was lower compared to healthy group (P < 0.05), and the fetal cardiac axis in conus arteriosus malformation group was significantly higher compared to healthy group (P < 0.05). Among the fetuses with conus arteriosus malformation, tetralogy of Fallot (TOF), transposition of the great arteries (TGA) and double outlet right ventricle (DORV) had the highest proportions, accounting for 38.00%, 18.29% and 17.58%, respectively. Among all types of conus arteriosus malformations, atresia pulmonary valve syndrome associated with TOF, persistent truncus arteriosus and DORV exhibited higher proportions of fetal cardiac axis abnormalities, at 75.00%, 36.84% and 27.03%, respectively, while TGA and interrupted aortic arch associated with B-type interruption had lower proportions of fetal cardiac axis abnormalities, at 2.60% and 4.55%, respectively. Genetic testing was conducted on 73 cases (17.34%) of fetuses with conus arteriosus malformation in this study. Among them, fetal cardiac axis abnormalities were considered positive for genetic results due to factors such as aneuploidy, copy number abnormalities, and single-gene pathogenicity. A total of 31 cases tested positive for genetic anomalies, with a positive rate of approximately 42.47%. Conclusion: In the middle pregnancy, the fetal cardiac axis in cases of conus arteriosus malformation was significantly higher than in normal fetuses. Moreover, there were variations in fetal cardiac axis among different types of conus arteriosus malformations, and these differences were notably associated with genetic diagnostic results.

Adsorption Behavior and Kinetics of 1,4-Dioxane by Carbon Aerogel.

1,4-dioxane is a potential carcinogen in water and is difficult to deal with due to its robust cycloether bond and complete miscibility with water. To remove 1,4-dioxane in an economically viable and environmentally friendly way, a series of carbon aerogels were synthesized as adsorbents for 1,4-dioxane. The experiment results showed that adsorption performances were closely related to the preparation conditions of carbon aerogels, such as the molar ratio, heating rate, pyrolysis temperature and residence time, which were carefully controlled. Scanning electron microscope analysis revealed the presence of a three-dimensional porous network structure in carbon aerogels. Brunauer-Emmett-Teller analysis results demonstrated an increase in specific surface area (673.89 m2/g) and total pore volume after carbonization, with an increase in mesoporous porosity and a decrease in microporosity. When considering each variable individually, the highest specific surface area of prepared carbon aerogels was achieved at a pyrolysis temperature of 800 °C, a holding time of 1 h, and a heating rate of 2 °C/min. Under optimal experimental conditions, the adsorption removal of 1,4-dioxane by carbon aerogels exceeded 95%, following quasi-second-order kinetics and Langmuir isothermal adsorption isotherms, indicating that monolayer adsorption on the surface of carbon aerogels occurred. The maximum adsorption capacity obtained was 67.28 mg/g at a temperature of 318 K, which was attributed to the presence of a large proportion of mesopores and abundant micropores simultaneously in carbon aerogels. Furthermore, with the interference of chlorinated solvents such as trichloroethylene (TCE), the removal efficiency of 1,4-dioxane had no obvious inhibition effect. Regeneration experiments showed that after five continuous cycles, the carbon aerogels still kept a comparable adsorption capacity, which illustrates its potential application in 1,4-dioxane-polluted water purification.

A novel GSK3ß inhibitor 5n attenuates acute kidney injury.

Acute kidney injury (AKI) is a clinical syndrome with high morbidity and mortality caused by various factor. The specific strategies for AKI are still lacking. GSK3ß is widely expressed in the kidneys. In acute models of injury, GSK3ß promotes the systemic inflammatory response, increases the proinflammatory release of cytokines, induces apoptosis, and alters cell proliferation. We screened a series of 3-(4-pyridyl)-5-(4-sulfamido-phenyl)-1,2,4-oxadiazole derivatives which are recognized as new GSK3ß inhibitors, and found that 5n had the least toxicity and the best cell protection. We then tested the anti-inflammatory and reno-protective effect of 5n in cisplatin-treated tubular epithelial cells. 5n had anti-inflammation effect indicated by phosphor-NF-κB detection. Finally, we found that 5n ameliorated renal injury and inflammation in cisplatin-induced AKI mouse model. Silencing GSK3ß inhibited cell injury and inflammation induced by cisplatin. We found that GSK3ß interacted with PP2Ac to modulate the activity of NF-κB. In conclusion, 5n, the novel GSK3ß inhibitor, protects against AKI via PP2Ac-dependent mechanisms which may provide a potential strategy for the treatment of AKI in clinic.

Safety, pharmacokinetics, and food effect of sudapyridine (WX-081), a novel anti-tuberculosis candidate in healthy Chinese subjects.

This study aimed to assess the safety, pharmacokinetics, and food impact on sudapyridine (WX-081), a novel drug designed to inhibit mycobacterium ATP synthase, with clinical applications for drug-resistant tuberculosis (TB) treatment. The research comprised two arms: a single ascending dose (SAD) arm (30 to 600 mg, N = 52) and a multiple ascending dose (MAD) arm (200 to 400 mg, N = 30). The influence of food was evaluated using a 400 mg dose within an SAD cohort. Plasma concentrations of WX-081 and M3 (main metabolite of WX-081) were analyzed using a validated liquid-chromatography tandem mass spectrometry method. In the SAD arm, mean residence time (MRT0-t), terminal half-life, and clearance of WX-081 ranged from 18.87 to 52.8 h, 31.39 to 236.57 h, and 6.4 to 80.34 L/h, respectively. The area under the curve from time zero to the last measurable timepoint (AUC0-t) of WX-081 showed dose-proportional increases in the SAD arm. The disparity between fasted and fed states of WX-081 was significant (p < 0.05), with fed dosing resulting in a 984.07% higher AUC0-t and 961.55% higher maximum plasma concentration. In both the SAD and MAD arms, one case each exhibited a 1 degree atrioventricular block. No QTc elongation was observed, and adverse events were not dose-dependent. Favorable exposure, tolerability, safety, and an extended MRT0-t suggest that WX-081 holds promise as a phase II development candidate for drug-resistant TB treatment.

Multiperformance PAM/PVA/CaCO3 Hydrogel for Flexible Sensing and Information Encryption.

Currently, the development of hydrogels with excellent mechanical properties (elasticity, fatigue resistance, etc.) and conductive properties can better meet their needs in the field of flexible sensor device applications. Generally, hydrogels with a denser cross-linking density tend to have better mechanical properties, but the improvement in mechanical properties comes at the expense of reduced electrical conductivity. Directly generating CaCO3 in the hydrogel prepolymer can not only increase the cross-linking density of its network but also introduce additional ions to enhance its internal ionic strength, which is beneficial to improving the conductivity of the hydrogel. It is still a big challenge to directly generate CaCO3 in the static prepolymer solution and ensure its uniform dispersion in the hydrogel. Herein, we adopted an improved preparation method to ensure that the directly generated CaCO3 particles can be evenly dispersed in the static prepolymer solution until the polymerization is completed. Finally, a PAM/PVA/CaCO3 hydrogel with supertensile, compressive, toughness, and fatigue resistance properties was prepared. In addition, the presence of free Na+ and Cl- gives the hydrogel excellent conductivity and sensing performance to monitor daily human activities. On the basis of the application of hydrogels in information communication, we have further deepened this application by combining the characteristics of hydrogels themselves. Combined with ASCII code, the hydrogel can also be applied in information exchange and information encryption and decryption, achieving the antitheft function in smart locks. A variety of excellent performance integrated PAM/PVA/CaCO3 hydrogels have broad application prospects for flexible sensors, highlighting great potential in human-computer interaction and intelligent information protection.

Electrochemical Dehydrogenative [3 + 2]/[5 + 2] Annulation of N-Arylacrylamides with γ,σ-Unsaturated Malonates via Direct C(sp3)-H/C(sp2)-H Functionalization.

Herein, we introduce an electrochemical dehydrogenative [3 + 2]/[5 + 2] annulation of easily available N-arylacrylamides with γ,σ-unsaturated malonates through C(sp3)-H/C(sp2)-H functionalization. The employment of inexpensive ferrocene as the redox catalyst allows access to diverse benzo[b]azepin-2-ones in moderate to excellent yields without stoichiometric oxidants. This protocol features broad substrate scope and excellent selectivity, and mechanistic studies indicated that the reaction proceeded through the oxidation of a C(sp3)-H bond to generate an alkyl radical, radical addition across the C═C bond, [3 + 2]/[5 + 2] annulations, and C(sp2)-H functionalization cascades.