CoNi-layered double hydroxide derived CoS2/NiS2 dodecahedron decorated with ReS2 Z-scheme heterojunction for efficient hydrogen evolution.

The high efficient utilization of light absorption and the effective separation of photogenerated carriers are critical factors in enhancing the performance of photocatalysts. In this study, CoNi-layered double hydroxide was synthesized using zeolitic imidazolate frameworks-67 as a template, followed by calcination to form CoS2/NiS2. Subsequently, ReS2 was deposited onto the surface of CoS2/NiS2, resulting in the ReS2/CoS2/NiS2 photocatalyst demonstrated notable hydrogen evolution activity under visible light, achieving a maximum hydrogen production rate of 40111.8 µmol/g. The construction of the Z-scheme heterojunction was found to facilitate the transfer and separation of photogenerated carriers while extending the lifetime of photogenerated electrons, thereby contributing to the enhancement of photocatalytic activity. This study provides a new approach for the development of sulfide heterojunctions aimed at improving photocatalytic hydrogen production efficiency.

Development of a Chitin-Based Purification System Utilizing Chitin-Binding Domain and Tobacco Etch Virus Protease Cleavage for Efficient Recombinant Protein Recovery.

This study aims to develop an efficient chitin-based purification system, leveraging a novel design where the target proteins, superfolding green fluorescent protein (sfGFP) and Thermus antranikianii trehalose synthase (TaTS), fused with a chitin-binding domain (ChBD) from Bacillus circulans WL-12 chitinase A1 and a tobacco etch virus protease (TEVp) cleavage site. This configuration allows for the effective immobilization of the target proteins on chitin beads, facilitating the removal of endogenous proteins. A mutant TEVp, H-TEVS219V-ChBD, fused with the His-tag and ChBD, is employed to cleave the target proteins from the chitin beads specifically. Subsequently, fresh chitin beads are added for adsorption to remove H-TEVS219V-ChBD in the solution, thereby significantly improving the purity of the target protein. Our results confirm that this system can efficiently and specifically purify and recover sfGFP and TaTS, achieving electrophoretic-grade purity exceeding 90%. This system holds significant potential for industrial production and other applications.

Genome-Wide Identification and Expression Analysis of MYB Transcription Factor Family in Response to Various Abiotic Stresses in Coconut (Cocos nucifera L.).

Abiotic stresses such as nitrogen deficiency, drought, and salinity significantly impact coconut production, yet the molecular mechanisms underlying coconut's response to these stresses are poorly understood. MYB proteins, a large and diverse family of transcription factors (TF), play crucial roles in plant responses to various abiotic stresses, but their genome-wide characterization and functional roles in coconut have not been comprehensively explored. This study identified 214 CnMYB genes (39 1R-MYB, 171 R2R3-MYB, 2 3R-MYB, and 2 4R-MYB) in the coconut genome. Phylogenetic analysis revealed that these genes are unevenly distributed across the 16 chromosomes, with conserved consensus sequences, motifs, and gene structures within the same subgroups. Synteny analysis indicated that segmental duplication primarily drove CnMYB evolution in coconut, with low nonsynonymous/synonymous ratios suggesting strong purifying selection. The gene ontology (GO) annotation of protein sequences provided insights into the biological functions of the CnMYB gene family. CnMYB47/70/83/119/186 and CnMYB2/45/85/158/195 were identified as homologous genes linked to nitrogen deficiency, drought, and salinity stress through BLAST, highlighting the key role of CnMYB genes in abiotic stress tolerance. Quantitative analysis of PCR showed 10 CnMYB genes in leaves and petioles and found that the expression of CnMYB45/47/70/83/85/119/186 was higher in 3-month-old than one-year-old coconut, whereas CnMYB2/158/195 was higher in one-year-old coconut. Moreover, the expression of CnMYB70, CnMYB2, and CnMYB2/158 was high under nitrogen deficiency, drought, and salinity stress, respectively. The predicted secondary and tertiary structures of three key CnMYB proteins involved in abiotic stress revealed distinct inter-proteomic features. The predicted interaction between CnMYB2/158 and Hsp70 supports its role in coconut's drought and salinity stress responses. These results expand our understanding of the relationships between the evolution and function of MYB genes, and provide valuable insights into the MYB gene family's role in abiotic stress in coconut.

The mechanism of action and chemical synthesis of FDA newly approved drug molecules.

In 2023, the U.S. Food and Drug Administration has approved 29 small molecule drugs. These newly approved small molecule drugs possess the distinct scaffolds, thereby exhibiting diverse mechanisms of action and binding modalities. Moreover, the marketed drugs have always been an important source of new drug development and creative inspiration, thereby fostering analogous endeavors in drug discovery that potentially extend to the diverse clinical indications. Therefore, conducting a comprehensive evaluation of drug approval experience and associated information will facilitate the expedited identification of highly potent drug molecules. In this review, we comprehensively summarized the relevant information regarding the clinical applications, mechanisms of action and chemical synthesis of 29 small molecule drugs, with the aim of providing a promising structural basis and design inspiration for pharmaceutical chemists.

Metal Halide Perovskite Nanocrystals-Intermediated Hydrogel for Boosting the Biosensing Performance.

Metal-halide perovskites have become attractive nanomaterials for advanced biosensors, yet the structural design remains challenging due to the trade-off between environmental stability and sensing sensitivity. Herein, a trinity strategy is proposed to address this issue by integrating Mn (II) substitution with CsPb2Cl5 inert shell and NH2-PEG-COOH coating for designing Mn2+-doped CsPbCl3/CsPb2Cl5 core/shell hetero perovskite nanocrystals (PMCP PNCs). The trinity strategy isolates the emissive Mn2+-doped CsPbCl3 core from water and the Mn2+ d-d transition generates photoluminescence with a long lifetime, endowing the NH2-PEG-COOH capped Mn2+-doped CsPbCl3/CsPb2Cl5 PNCs with robust water stability and oxygen-sensitive property. Given the structural integration, photoluminescent hydrogel biosensors are designed by embedding the PMCP PNCs into the hydrogel system to deliver on-site pesticide information on food products. Impressively, benefiting from the dual enzyme triggered-responsive property of PMCP PNCs, the hydrogel biosensor is endowed with ultra-high sensitivity toward chlorpyrifos pesticide at the nanogram per milliliter level. Such a robust PMCP PNCs-based hydrogel sensor can provide accurate pesticide information while guiding the construction of photoluminescent biosensors for upcoming on-site applications.

Lighting Up Nonemissive Azobenzene Derivatives by Pressure.

Pressure-induced emission (PIE) is a compelling phenomenon that can activate luminescence within nonemissive materials. However, PIE in nonemissive organic materials has never been achieved. Herein, we present the first observation of PIE in an organic system, specifically within nonemissive azobenzene derivatives. The emission of 1,2-bis(4-(anthracen-9-yl)phenyl)diazene was activated at 0.52 GPa, primarily driven by local excitation promotion induced by molecular conformational changes. Complete photoisomerization suppression of the molecule was observed at 1.5 GPa, concurrently accelerating the emission enhancement to 3.53 GPa. Differing from the key role of isomerization inhibition in conventional perception, our findings demonstrate that the excited-state constituent is the decisive factor for emission activation, providing a potentially universal approach for high-efficiency azobenzene emission. Additionally, PIE was replicated in the analogue 1,2-bis(4-(9H-carbazol-9-yl)phenyl)diazene, confirming the general applicability of our findings. This work marks a significant breakthrough within the PIE paradigm and paves the novel high-pressure route for crystalline-state photoisomerization investigation.

CircUGP2 Suppresses Intrahepatic Cholangiocarcinoma Progression via p53 Signaling Through Interacting With PURB to Regulate ADGRB1 Transcription and Sponging miR-3191-5p.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and its prognosis remains poor. Although growing numbers of studies have verified the involvement of circular RNAs (circRNAs) in various cancer types, their specific functions in ICC remain elusive. Herein, a circRNA, circUGP2 is identified by circRNA sequencing, which is downregulated in ICC tissues and correlated with patients' prognosis. Moreover, circUGP2 overexpression suppresses tumor progression in vitro and in vivo. Mechanistically, circUGP2 functions as a transcriptional co-activator of PURB over the expression of ADGRB1. It can also upregulate ADGRB1 expression by sponging miR-3191-5p. As a result, ADGRB1 prevents MDM2-mediated p53 polyubiquitination and thereby activates p53 signaling to inhibit ICC progression. Based on these findings, circUGP2 plasmid is encapsulated into a lipid nanoparticle (LNP) system, which has successfully targeted tumor site and shows superior anti-tumor effects. In summary, the present study has identified the role of circUGP2 as a tumor suppressor in ICC through regulating ADGRB1/p53 axis, and the application of LNP provides a promising translational strategy for ICC treatment.

A comprehensive review of new small molecule drugs approved by the FDA in 2022: Advance and prospect.

In 2022, the U.S. Food and Drug Administration approved a total of 16 marketing applications for small molecule drugs, which not only provided dominant scaffolds but also introduced novel mechanisms of action and clinical indications. The successful cases provide valuable information for optimizing efficacy and enhancing pharmacokinetic properties through strategies like macrocyclization, bioequivalent group utilization, prodrug synthesis, and conformation restriction. Therefore, gaining an in-depth understanding of the design principles and strategies underlying these drugs will greatly facilitate the development of new therapeutic agents. This review focuses on the research and development process of these newly approved small molecule drugs including drug design, structural modification, and improvement of pharmacokinetic properties to inspire future research in this field.

Correlation analysis of human papillomavirus E6/E7 mRNA detection with diagnosis, prognosis and recurrence risk in patients with cervical epithelioma.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) is an important precursor of cervical cancer. Early detection and treatment can reduce the incidence of cervical cancer. AIM: To investigate the detection rate of human papillomavirus (HPV) E6/E7 mRNA in cervical tissue of patients with different types of epithelial cell neoplasia (CIN) and its relationship with CIN progression and diagnosis. METHODS: One hundred women with HPV infection detected by cervical exfoliation cytology between January 2022 and January 2023 were retrospectively selected. These patients were graded CIN based on colposcopy and cervical pathology. The positive expression rates of HPV E6/E7 mRNA and HPV [polymerase chain reaction (PCR)-reverse dot crossing] were compared among all groups. Patients with HPV E6/E7 mRNA expression in the grade 1 CIN group were followed up for 1 yr. The relationship between atypical squamous epithelium and high malignant epithelial neoplasia was investigated by univariate and multivariate analysis. RESULTS: The diagnostic sensitivity, specificity, and sensitivity of PCR-reverse point hybridization technology for secondary CIN were 70.41%, 70.66%, and 0.714, respectively. Sensitivity and specificity for secondary CIN were 752% and 7853%, respectively, the area under the curve value was 0.789. Logistic Multifactorial model analysis revealed that the HPV positive rates and the HPV E6/E7 mRNA positive rates were independent risk factors of CIN grade I (P < 0.05). In CIN grade I patients with positive for HPV E6/E7 mRNA, in its orientation to grade CIN patients, in its orientation to grade CIN patients, at 69.2%, compared with patients negative for HPV E6/E7 mRNA (30.8%), significant difference (P < 0.05). CONCLUSION: HPV E6/E7 mRNA and HPV (PCR-reverse dot hybrid) positive expression have a close relationship with CIN-grade disease progression and is an independent risk factor for high-grade CIN lesions.

Carbon dots-based stimuli-responsive hydrogel for in-situ detection of thiram on fruits and vegetables.

Stimuli-responsive hydrogel possesses a strong loading capacity to embed luminescent indicators for constructing food safety sensors, which are suitable for field application. In this work, a fluorescent hydrogel sensor was fabricated by incorporating Ag+-modified carbon dots (CDs-Ag+) into a sodium alginate (SA) hydrogel for in-situ detection of thiram. The fluorescence of CDs was quenched due to the combined effects of electrostatic adsorption and electron transfer between Ag+ and CDs. The formation of an AgS bond between thiram and Ag+ facilitates the release of CDs, causing subsequently fluorescence recovery. Combined with smartphone and analysis software, the fluorescence color change of the hydrogel sensor was converted into data information for quantitative detection of thiram. Such a sample-to-result step is completed within 10 min. Notably, the in-situ detection experiment of thiram in fruit and vegetable samples confirmed the practical application of the hydrogel sensor. Therefore, the hydrogel sensor provides a new research direction for the in-situ detection of pesticide residues in the monitoring of food safety.

A comprehensive review of small molecule drugs approved by the FDA in 2023: Advances and prospects.

In 2023, the U.S. Food and Drug Administration has approved 55 novel medications, consisting of 17 biologics license applications and 38 new molecular entities. Although the biologics license applications including antibody and enzyme replacement therapy set a historical record, the new molecular entities comprising small molecule drugs, diagnostic agent, RNA interference therapy and biomacromolecular peptide still account for over 50 % of the newly approved medications. The novel and privileged scaffolds derived from drugs, active molecules and natural products are consistently associated with the discovery of new mechanisms, the expansion of clinical indications and the reduction of side effects. Moreover, the structural modifications based on the promising scaffolds can provide the clinical candidates with the improved biological activities, bypass the patent protection and greatly shorten the period of new drug discovery. Therefore, conducting an appraisal of drug approval experience and related information will expedite the identification of more potent drug molecules. In this review, we comprehensively summarized the pertinent information encompassing the clinical application, mechanism, elegant design and development processes of 28 small molecule drugs, and expected to provide the promising structural basis and design inspiration for pharmaceutical chemists.

Primary leiomyosarcoma of epididymis: a case report.

BACKGROUND: Leiomyosarcoma is a tumor that can develop in any organ that contains smooth muscles. Although leiomyosarcoma is common, its epididymal localization is quite rare. CASE PRESENTATION: A 79-year-old male Chinese Han patient presented with mild pain in the right groin and scrotum for 3 years concomitant with right scrotal swelling. Ultrasonography and magnetic resonance imaging of the scrotum showed a irregular and heterogeneous mass that was extratesticular. Right high orchiectomy was performed, and pathological examination of the resected specimen confirmed the diagnosis of leiomyosarcoma of the epididymis with surgical margins clear of tumor. CONCLUSION: Epididymal leiomyosarcoma is rare and difficult to diagnose preoperatively. The final diagnosis of epididymal leiomyosarcoma requires histologic examination. Resection must be extensive and complete. The effect of chemotherapy and radiation on the epididymal leiomyosarcoma remains unclear. Recurrence is common, so follow-up is necessary.

Using a Large Language Model to Identify Adolescent Patient Portal Account Access by Guardians.

This diagnostic/prognostic study assesses the ability of a large language model (LLM) to detect guardian authorship of messages originating from adolescent patient portals.

Ligand-Accelerated Pd-Catalyzed C(sp2)-H and C(sp3)-H Arylation under the Catalytic System.

It is universally acknowledged that ligands can improve the reaction activity to simplify the reaction operating conditions and enrich the applicability of the reaction. Therefore, we developed N-octylglycine ligand-accelerated Pd-catalyzed ortho-arylation of benzoic acids under mild conditions with just 6 h; moreover, this N-octylglycine ligand was successfully implemented to carboxyl-directed Pd-catalyzed ß-C(sp3)-H arylation and ortho-arylation of phenylacetic acids under mild conditions.

Study on the impact of smart city construction on the health of the elderly population--A quasi-natural experiment in China.

In the context of global aging, promoting the health of the elderly has become a critical issue. However, whether the development of smart cities can impact the health of older adults remains to be further validated. In this paper, based on panel data from the China Health and Retirement Longitudinal Study (CHARLS), a difference in difference model is used to empirically investigate whether smart city construction improves the health of older people in the region. The results show that smart city construction enhances the health of the elderly. Specifically, the construction achieved a significant improvement in the physical health of the elderly who did not live with their children. The health promotion effect of the smart city was more significant for the urban elderly than for the rural elderly. The elucidated mechanisms of influence suggest that smart cities bring about their effects through the promotion of urban leisure infrastructure, enhancement of medical service provision, advancement in urban environmental protection and stimulation of urban information and communication technology infrastructure development.

Enhancing crystal integrity and structural rigidity of CsPbBr3 nanoplatelets to achieve a narrow color-saturated blue emission.

Quantum-confined CsPbBr3 perovskites are promising blue emitters for ultra-high-definition displays, but their soft lattice caused by highly ionic nature has a limited stability. Here, we endow CsPbBr3 nanoplatelets (NPLs) with atomic crystal-like structural rigidity through proper surface engineering, by using strongly bound N-dodecylbenzene sulfonic acid (DBSA). A stable, rigid crystal structure, as well as uniform, orderly-arranged surface of these NPLs is achieved by optimizing intermediate reaction stage, by switching from molecular clusters to mono-octahedra, while interaction with DBSA resulted in formation of a CsxO monolayer shell capping the NPL surface. As a result, both structural and optical stability of the CsPbBr3 NPLs is enhanced by strong covalent bonding of DBSA, which inhibits undesired phase transitions and decomposition of the perovskite phase potentially caused by ligand desorption. Moreover, rather small amount of DBSA ligands at the NPL surface results in a short inter-NPL spacing in their closely-packed films, which facilitates efficient charge injection and transport. Blue photoluminescence of the produced CsPbBr3 NPLs is bright (nearly unity emission quantum yield) and peaks at 457 nm with an extremely narrow bandwidth of 3.7 nm at 80 K, while the bandwidth of the electroluminescence (peaked at 460 nm) also reaches a record-narrow value of 15 nm at room temperature. This value corresponds to the CIE coordinates of (0.141, 0.062), which meets Rec. 2020 standards for ultra-high-definition displays.

Paclitaxel inhibits proliferation by negatively regulating Cdk1-cell cycle axis in rat airway smooth muscle cells.

OBJECTIVE: Paclitaxel exhibits outstanding biological activities in inhibiting cell proliferation and inducing cell apoptosis. However, the effects of paclitaxel on airway smooth muscle cells (ASMCs) have not been reported yet. The purpose of this study is to determine the effects of paclitaxel on the proliferation and apoptosis of ASMCs. METHODS: Rat primary ASMCs were isolated and used in all the experiments. Cell Counting Kit-8 assay and Edu assay were used to analyze the cell viability and proliferation, respectively. Flow cytometry was used to detect the cell cycle and apoptosis. Quantitative real-time PCR (qRT-PCR), western blotting, and immunostaining were used to detect the expression of cyclin-dependent kinase 1 (Cdk1). RESULTS: Our study showed that paclitaxel inhibits the proliferation of ASMCs in a dose- and time-gradient-dependent manner. Further study displayed that cell cycle is arrested at G2/M phase. And Cdk1 was dramatically down-regulated by paclitaxel treatment. Cell morphological analysis showed that ASMCs are elliptical with a larger surface area after paclitaxel treatment. Nucleus morphological analysis showed that the nuclei are in a diffuse state after paclitaxel treatment. However, paclitaxel did not induce the apoptosis of ASMCs. CONCLUSIONS: Our study demonstrated that paclitaxel inhibits the proliferation of ASMCs at least partly by negatively regulating Cdk1-cell cycle axis.

Trehalose improves the movement ability of AßarcDrosophila by restoring the damaged mitochondria.

Background: The deposition of Aß42 has been regarded as one of the important pathological features of Alzheimer's disease (AD). However, drug development for Aß42 toxicity has been progressed slowly. Objective: Our aim was to introduce the effect and related mechanism of trehalose on an Aßarc (arctic mutant Aß42) Drosophila AD model. Methods: The human Aßarc was expressed in Drosophila to construct the AD model. Trehalose was added to the culture vial. The movement ability was determined by detecting climbing ability and flight ability. Enzyme-linked immunosorbent assay was used to detect the levels of Aßarc, ATP, and lactate. Electron microscopy assay, mitochondrial membrane potential assay, and mitochondrial respiration assay were used to assess the mitochondrial structure and function. Results: Trehalose strongly improved the movement ability of Aßarc Drosophila in a concentration gradient-dependent manner. Furthermore, trehalose increased the content of ATP and decreased the content of Aßarc and lactate both in the brain and thorax of Aßarc Drosophila. More importantly, the mitochondrial structure and function were greatly improved by trehalose treatment in Aßarc Drosophila. Conclusion: Trehalose improves movement ability at least partly by reducing the Aßarc level and restoring the mitochondrial structure and function in Aßarc Drosophila.

Primary Nasopharyngeal Melanoma without invasive and Metastasis: A Rare Case Reports and Literature Reviews.

Objective: Nasopharyngeal melanoma is a rare mucosal malignant melanoma with high recurrence rate, metastasis rate and vascular invasion rate. In this paper, we report a case of primary nasopharyngeal mucosal melanoma. Methods: A case of primary nasopharyngeal mucosal melanoma was reported, and its clinical symptoms, pathological characteristics, treatment and follow-up were described in detail. Results: This report describes a 59-year-old male patient with persistent nasal congestion and suspected malignant nasopharyngeal neoplasm. Patients receive surgical resection and adjuvant radiotherapy after complete resection. Imaging studies showed no tissue invasion or lymph node metastases. The results of immunohistochemistry were Melan-A(+), HMB45(+), and S100(+). The final diagnosis was malignant nasopharyngeal melanoma. After 2 years of follow-up, the prognosis was good, and there was no metastasis or recurrence. Discussion: Nasopharyngeal melanoma is a rare malignancy with a poor prognosis, and surgical resection is the mainstay of treatment. Postoperative adjuvant therapy can improve the rate of local control of lesions. Early diagnosis and thorough examination are extremely important for the patient's prognosis.