Screening of genes co-associated with osteoporosis and chronic HBV infection based on bioinformatics analysis and machine learning.

Objective: To identify HBV-related genes (HRGs) implicated in osteoporosis (OP) pathogenesis and develop a diagnostic model for early OP detection in chronic HBV infection (CBI) patients. Methods: Five public sequencing datasets were collected from the GEO database. Gene differential expression and LASSO analyses identified genes linked to OP and CBI. Machine learning algorithms (random forests, support vector machines, and gradient boosting machines) further filtered these genes. The best diagnostic model was chosen based on accuracy and Kappa values. A nomogram model based on HRGs was constructed and assessed for reliability. OP patients were divided into two chronic HBV-related clusters using non-negative matrix factorization. Differential gene expression analysis, Gene Ontology, and KEGG enrichment analyses explored the roles of these genes in OP progression, using ssGSEA and GSVA. Differences in immune cell infiltration between clusters and the correlation between HRGs and immune cells were examined using ssGSEA and the Pearson method. Results: Differential gene expression analysis of CBI and combined OP dataset identified 822 and 776 differentially expressed genes, respectively, with 43 genes intersecting. Following LASSO analysis and various machine learning recursive feature elimination algorithms, 16 HRGs were identified. The support vector machine emerged as the best predictive model based on accuracy and Kappa values, with AUC values of 0.92, 0.83, 0.74, and 0.7 for the training set, validation set, GSE7429, and GSE7158, respectively. The nomogram model exhibited AUC values of 0.91, 0.79, and 0.68 in the training set, GSE7429, and GSE7158, respectively. Non-negative matrix factorization divided OP patients into two clusters, revealing statistically significant differences in 11 types of immune cell infiltration between clusters. Finally, intersecting the HRGs obtained from LASSO analysis with the HRGs identified three genes. Conclusion: This study successfully identified HRGs and developed an efficient diagnostic model based on HRGs, demonstrating high accuracy and strong predictive performance across multiple datasets. This research not only offers new insights into the complex relationship between OP and CBI but also establishes a foundation for the development of early diagnostic and personalized treatment strategies for chronic HBV-related OP.

Nitrogen-rich and core-sheath polyamide/polyethyleneimine@Zr-MOF for iodine adsorption and nerve agent simulant degradation.

Radioactive nuclides and highly toxic organophosphates are typical deadly threats. Materials with the function of radioactive substances adsorption and organophosphates degradation provide double protection. Herein, dual-functional polyamide (PA)/polyethyleneimine (PEI)@Zr-MOF fiber composite membranes, fabricated by in-situ solvothermal growth of Zr-MOF on PA/PEI electrospun fiber membranes, are designed for protection against two typical model compounds of iodine and dimethyl 4-nitrophenyl phosphate (DMNP). Benefiting from the unique core-sheath structure composed of inner nitrogen-rich fibers and outer porous Zr-MOF, the composite membranes rapidly enrich iodine through abundant active sites of the outer sheath and form complexes with the amine of inner PEI, exhibiting a highly competitive adsorption capacity of 609 mg g-1. Moreover, it can adsorb and degrade DMNP with the synergy of PEI component and Zr-MOF, achieving an 80 % removal of DMNP within 7 min without any additional co-catalyst. This work provides a feasible strategy to fabricate dual-functional materials that protect against radioactive and organophosphorus contaminants.

Innovative medicinal chemistry strategies for enhancing drug solubility.

Drug candidates with poor solubility have been recognized as the cause of many drug development failures, owing to the fact that low solubility is unfavorable for physicochemical, pharmacokinetic (PK) and pharmacodynamic (PD) properties. Given the imperative role of solubility during drug development, we herein summarize various strategies for solubility optimizations from a medicinal chemistry perspective, including introduction of polar group, salt formation, structural simplification, disruption of molecular planarity and symmetry, optimizations on the solvent exposed region as well as prodrug design. In addition, methods for solubility assessment and prediction are reviewed. Besides, we have deeply discussed the strategies for solubility improvement. This paper is expected to be beneficial for the development of drug-like molecules with good solubility.

Enhancing skeletal muscle fiber characteristics, intramuscular fat deposition and fatty acid composition in broilers under heat stress through combined selenomethionine and Bacillus subtilis supplementation in the diet.

Heat stress is the most common environmental stressor in poultry production, negatively affecting growth performance, meat quality, and welfare. Therefore, the aim of this study was to compare the nutritional effects of dietary supplementation with selenomethionine, BS, and a combination of selenomethionine and BS on broilers challenged with heat stress. A total of 300 21-day-old Ross 308 male broilers were randomly assigned to 5 groups with 6 replicates of 10 broilers per each: control group (CON, broilers raised at 22 ± 2℃); heat stress exposure group (HS, broilers raised at 32 ± 2℃ for 8 h/day); HSS group (HS group supplemented with 0.3 mg/kg selenomethionine); HSB group (HS group supplemented with 1 × 109 cfu/kg BS); and HSBS group (HS group supplemented with 0.3 mg/kg selenomethionine and × 109 cfu/kg BS). The experiment lasted for 21 days. The results indicated that, compared to the CON group, heat stress reduces (P < 0.05) broiler growth performance and damages the meat quality in breast and thigh muscles. Dietary supplementation with selenomethionine and BS did not improve the growth performance of broilers under heat stress. However, compared to the HS group, the HSS, HSB, and HSBS groups showed significantly increased (P < 0.05) pH45 min, redness (a*) and yellowness (b*), muscle fiber density, intramuscular fat (IMF), triglyceride content (TG), and expression levels of Myf5, CAPN 2, FM, SLC27A1, A-FABP, H-FABP, APOB-100, and ACC in breast and thigh muscles. Meanwhile, these groups showed reduced (P < 0.05) lightness (L*), drip loss, shear force, muscle fiber cross-sectional area, and FM gene expression level. The HSBS group showed greater improvement in the physicochemical quality of muscle and volatile substances compared to the HSS and HSB groups. In conclusion, selenomethionine and BS improved meat quality and flavor in broilers under heat stress by modulating muscle fiber composition and characteristics, as well as increasing intramuscular fat deposition.

Synthesis of the Corrected Structure Assigned to Clonorosin B, an Alkaloid Obtained from the Soil-derived Fungus Clonostachys rosea YRS-06.

The revised structure, 2, assigned to the title natural product has been prepared by chemical synthesis using a reaction sequence involving six simple steps starting from 2,3-dimethoxybenzaldehyde and proceeding via intermediates 8, 12, and 14. A comparison of the NMR data acquired on synthetically derived compound 2 with those reported for the natural product reveals an excellent match. Preliminary biological screening of compound 2 along with analogues/precursors 7, 9, 10, 11, 13, 14, and 15 revealed that none exhibited antibacterial, antifungal or cytotoxic effects.

Synthesis of nicotinimidamides via a tandem CuAAC/ring-cleavage /cyclization/oxidation four-component reaction and their cytotoxicity.

Nicotinamide and its derivatives, recognized as crucial drug intermediates, have been a focal point of extensive chemical modifications and rigorous pharmacological studies. Herein, a series of novel nicotinamide derivatives, nicotinimidamides, were synthesized via a tandem CuAAC/ring-cleavage/cyclization/oxidation four-component reaction procedure from O-acetyl oximes, terminal ynones, sulfonyl azides, and NH4OAc. This strategy is significantly more efficient than previously reported, and the cytotoxicity of the nicotinimidamides is also tested. This project not only exhibits a sustainable and eco-friendly domino methodology for the creation of nicotinimidamides but also presents a promising candidate for liver cancer treatment.

The recent advance and prospect of poly(ADP-ribose) polymerase inhibitors for the treatment of cancer.

Chemotherapies are commonly used in cancer therapy, their applications are limited to low specificity, severe adverse reactions, and long-term medication-induced drug resistance. Poly(ADP-ribose) polymerase (PARP) inhibitors are a novel class of antitumor drugs developed to solve these intractable problems based on the mechanism of DNA damage repair, which have been widely applied in the treatment of ovarian cancer, breast cancer, and other cancers through inducing synthetic lethal effect and trapping PARP-DNA complex in BRCA gene mutated cancer cells. In recent years, PARP inhibitors have been widely used in combination with various first-line chemotherapy drugs, targeted drugs and immune checkpoint inhibitors to expand the scope of clinical application. However, the intricate mechanisms underlying the drug resistance to PARP inhibitors, including the restoration of homologous recombination, stabilization of DNA replication forks, overexpression of drug efflux protein, and epigenetic modifications pose great challenges and desirability in the development of novel PARP inhibitors. In this review, we will focus on the mechanism, structure-activity relationship, and multidrug resistance associated with the representative PARP inhibitors. Furthermore, we aim to provide insights into the development prospects and emerging trends to offer guidance for the clinical application and inspiration for the development of novel PARP inhibitors and degraders.

Sleeve lobectomy versus pneumonectomy following neoadjuvant therapy in patients with non-small cell lung cancer.

OBJECTIVES: Neoadjuvant therapy has gained widespread acceptance as the standard modality for locally advanced non-small cell lung cancer. However, the clinical benefit of sleeve lobectomy (SL) or pneumonectomy (PN) following neoadjuvant therapy remains controversial. METHODS: The clinical and pathological characteristics of non-small cell lung cancer patients who underwent SL or PN after neoadjuvant therapy at a high-volume single centre between December 2019 and March 2023 were retrospectively collected. The SL group was matched 4:1 with the PN group by propensity score matching. The surgical outcomes were systematically collected and analysed. RESULTS: During a 5-year study period, the majority of patients (175 of 215, 81.4%) underwent the SL procedure, while 40 patients (18.6%) underwent PN. Following propensity score matching, the SL group exhibited lower postoperative arrythmia (4.8% vs 26.9%, P < 0.001), lower 30-day mortality (1.0% vs 7.7%, P = 0.046) and a shorter length of postoperative hospital stay (6.0 days vs 10.0 days, P < 0.001), compared with the PN group. In addition, no significant difference was observed between the two groups in terms of disease-free survival or overall survival (P = 0.977 and P = 0.913, respectively). CONCLUSIONS: SL stands as a safe and feasible option for patients with centrally located non-small-cell lung cancer who have undergone neoadjuvant therapy, in comparison to PN. This finding suggests that SL remains the preferable choice when feasible in the context of the widespread utilization of neoadjuvant therapy.

Twisted MoSe2 Homobilayer Behaving as a Heterobilayer.

Heterostructures (HSs) formed by the transition-metal dichalcogenide materials have shown great promise in next-generation (opto)electronic applications. An artificially twisted HS allows us to manipulate the optical and electronic properties. In this work, we introduce the understanding of the energy transfer (ET) process governed by the dipolar interaction in a twisted molybdenum diselenide (MoSe2) homobilayer without any charge-blocking interlayer. We fabricated an unconventional homobilayer (i.e., HS) with a large twist angle (∼57°) by combining the chemical vapor deposition (CVD) and mechanical exfoliation (Exf.) techniques to fully exploit the lattice parameter mismatch and indirect/direct (CVD/Exf.) bandgap nature. These effectively weaken the interlayer charge transfer and allow the ET to control the carrier recombination channels. Our experimental and theoretical results explain a massive HS photoluminescence enhancement due to an efficient ET process. This work shows that the electronically decoupled MoSe2 homobilayer is coupled by the ET process, mimicking a "true" heterobilayer nature.

Synthesis of Pyridin-2(1H)-imines via the Transformation of Conjugated Ynones.

Conjugated ynones represent an important class of reactive species, useful synthetic intermediates, and synthons. However, the reactivity and synthetic applications of ynones are usually focused on the transformation of mono- or dual-functional groups. Herein, we developed a straightforward synthesis of pyridin-2(1H)-imines from the transformation of conjugated ynones. This cascade process probably began with a Michael addition of ynones and 2-aminopyridines, further underwent an intramolecular cyclization to generate the N,O-bidentate intermediates, and finally reacted with sulfonyl azides giving the pyridin-2(1H)-imines with accompanying loss of diazo.

Unveiling research trends in the prognosis of osteosarcoma: A bibliometric analysis from 2000 to 2022.

Background: Osteosarcoma (OSA) is the most prevalent form of malignant bone tumor in children and adolescents, producing osteoid and immature bone. Numerous high quality studies have been published in the OSA field, however, no bibliometric study related to this area has been reported thus far. Therefore, the present study retrieved the published data from 2000 to 2022 to reveal the dynamics, development trends, hotspots and future directions of the OSA. Methods: Publications regard to osteogenic sarcoma and prognosis were searched in the core collection on Web of Science database. The retrieved publications were analyzed by publication years, journals, categories, countries, citations, institutions, authors, keywords and clusters using the two widely available bibliometric visualization tools, VOS viewer (Version 1.6.16), Citespace (Version 6.2. R1). Results: A total of 6260 publications related to the current topic were retrieved and analyzed, revealing exponential increase in the number of publications with an improvement in the citations on the OSA over time, in which China and the USA are the most productive nations. Shanghai Jiao Tong University, University of Texas System and Harvard University are prolific institutions, having highest collaboration network. Oncology Letters and Journal of Clinical Oncology are the most productive and the most cited journals respectively. The Wang Y is a prominent author and articles published by Bacci G had the highest number of citations indicating their significant impact in the field. According to keywords analysis, osteosarcoma, expression and metastasis were the most apparent keywords whereas the current research hotspots are biomarker, tumor microenvironment, immunotherapy and DNA methylation. Conclusion: Our findings offer valuable information for researchers to understand the current research status and the necessity of future research to mitigate the mortality of the OS patients.

Computational approaches for mechanobiology in cardiovascular development and diseases.

The cardiovascular development in vertebrates evolves in response to genetic and mechanical cues. The dynamic interplay among mechanics, cell biology, and anatomy continually shapes the hydraulic networks, characterized by complex, non-linear changes in anatomical structure and blood flow dynamics. To better understand this interplay, a diverse set of molecular and computational tools has been used to comprehensively study cardiovascular mechanobiology. With the continual advancement of computational capacity and numerical techniques, cardiovascular simulation is increasingly vital in both basic science research for understanding developmental mechanisms and disease etiologies, as well as in clinical studies aimed at enhancing treatment outcomes. This review provides an overview of computational cardiovascular modeling. Beginning with the fundamental concepts of computational cardiovascular modeling, it navigates through the applications of computational modeling in investigating mechanobiology during cardiac development. Second, the article illustrates the utility of computational hemodynamic modeling in the context of treatment planning for congenital heart diseases. It then delves into the predictive potential of computational models for elucidating tissue growth and remodeling processes. In closing, we outline prevailing challenges and future prospects, underscoring the transformative impact of computational cardiovascular modeling in reshaping cardiovascular science and clinical practice.

Patient-specific computational flow simulation reveals significant differences in paravisceral aortic hemodynamics between fenestrated and branched endovascular aneurysm repair.

Background: Endovascular aneurysm repair with four-vessel fenestrated endovascular aneurysm repair (fEVAR) or branched endovascular aneurysm repair (bEVAR) currently represent the forefront of minimally invasive complex aortic aneurysm repair. This study sought to use patient-specific computational flow simulation (CFS) to assess differences in postoperative hemodynamic effects associated with fEVAR vs bEVAR. Methods: Patients from two institutions who underwent four-vessel fEVAR with the Cook Zenith Fenestrated platform and bEVAR with the Jotec E-xtra Design platform were retrospectively selected. Patients in both cohorts were treated for paravisceral and extent II, II, and V thoracoabdominal aortic aneurysms. Three-dimensional finite element volume meshes were created from preoperative and postoperative computed tomography scans. Boundary conditions were adjusted for body surface area, heart rate, and blood pressure. Pulsatile flow simulations were performed with equivalent boundary conditions between preoperative and postoperative states. Postoperative changes in hemodynamic parameters were compared between the fEVAR and bEVAR groups. Results: Patient-specific CFS was performed on 20 patients (10 bEVAR, 10 fEVAR) with a total of 80 target vessels (40 renal, 20 celiac, 20 superior mesenteric artery stents). bEVAR was associated with a decrease in renal artery peak flow rate (-5.2% vs +2.0%; P < .0001) and peak pressure (-3.4 vs +0.1%; P < .0001) compared with fEVAR. Almost all renal arteries treated with bEVAR had a reduction in renal artery perfusion (n = 19 [95%]), compared with 35% (n = 7) treated with fEVAR. There were no significant differences in celiac or superior mesenteric artery perfusion metrics (P = .10-.27) between groups. Time-averaged wall shear stress in the paravisceral aorta and branches also varied significantly depending on endograft configuration, with bEVAR associated with large postoperative increases in renal artery (+47.5 vs +13.5%; P = .002) and aortic time-averaged wall shear stress (+200.1% vs -31.3%; P = .001) compared with fEVAR. Streamline analysis revealed areas of hemodynamic abnormalities associated with branched renal grafts which adopt a U-shaped geometry, which may explain the observed differences in postoperative changes in renal perfusion between bEVAR and fEVAR. Conclusions: bEVAR may be associated with subtle decreases in renal perfusion and a large increase in aortic wall shear stress compared with fEVAR. CFS is a novel tool for quantifying and visualizing the unique patient-specific hemodynamic effect of different complex EVAR strategies. Clinical Relevance: This study used patient-specific CFS to compare postoperative hemodynamic effects of four-vessel fenestrated endovascular aneurysm repair (fEVAR) and branched endovascular aneurysm repair (bEVAR) in patients with complex aortic aneurysms. The findings indicate that bEVAR may result in subtle reductions in renal artery perfusion and a significant increase in aortic wall shear stress compared with fEVAR. These differences are clinically relevant, providing insights for clinicians choosing between these approaches. Understanding the patient-specific hemodynamic effects of complex EVAR strategies, as revealed by CFS, can aid in future personalized treatment decisions, and potentially reduce postoperative complications in aortic aneurysm repair.

High Shear Stress Reduces ERG Causing Endothelial-Mesenchymal Transition and Pulmonary Arterial Hypertension.

Pathological high shear stress (HSS, 100 dyn/cm 2 ) is generated in distal pulmonary arteries (PA) (100-500 µm) in congenital heart defects and in progressive PA hypertension (PAH) with inward remodeling and luminal narrowing. Human PA endothelial cells (PAEC) were subjected to HSS versus physiologic laminar shear stress (LSS, 15 dyn/cm 2 ). Endothelial-mesenchymal transition (EndMT), a feature of PAH not previously attributed to HSS, was observed. H3K27ac peaks containing motifs for an ETS-family transcription factor (ERG) were reduced, as was ERG-Krüppel-like factors (KLF)2/4 interaction and ERG expression. Reducing ERG by siRNA in PAEC during LSS caused EndMT; transfection of ERG in PAEC under HSS prevented EndMT. An aorto-caval shunt was preformed in mice to induce HSS and progressive PAH. Elevated PA pressure, EndMT and vascular remodeling were reduced by an adeno-associated vector that selectively replenished ERG in PAEC. Agents maintaining ERG in PAEC should overcome the adverse effect of HSS on progressive PAH.

Design of Optical System for Ultra-Large Range Line-Sweep Spectral Confocal Displacement Sensor.

The spectrum confocal displacement sensor is an innovative type of photoelectric sensor. The non-contact advantages of this method include the capacity to obtain highly accurate measurements without inflicting any harm as well as the ability to determine the object's surface contour recovery by reconstructing the measurement data. Consequently, it has been widely used in the field of three-dimensional topographic measuring. The spectral confocal displacement sensor consists of a light source, a dispersive objective, and an imaging spectrometer. The scanning mode can be categorized into point scanning and line scanning. Point scanning is inherently present when the scanning efficiency is low, resulting in a slower measurement speed. Further improvements are necessary in the research on the line-scanning type. It is crucial to expand the measurement range of existing studies to overcome the limitations encountered during the detection process. The objective of this study is to overcome the constraints of the existing line-swept spectral confocal displacement sensor's limited measuring range and lack of theoretical foundation for the entire system. This is accomplished by suggesting an appropriate approach for creating the optical design of the dispersive objective lens in the line-swept spectral confocal displacement sensor. Additionally, prism-grating beam splitting is employed to simulate and analyze the imaging spectrometer's back end. The combination of a prism and a grating eliminates the spectral line bending that occurs in the imaging spectrometer. The results indicate that a complete optical pathway for the line-scanning spectral confocal displacement sensor has been built, achieving an axial resolution of 0.8 µm, a scanning line length of 24 mm, and a dispersion range of 3.9 mm. This sensor significantly expands the range of measurements and fills a previously unaddressed gap in the field of analyzing the current stage of line-scanning spectral confocal displacement sensors. This is a groundbreaking achievement for both the sensor itself and the field it operates in. The line-scanning spectral confocal displacement sensor's design addresses a previously unmet need in systematic analysis by successfully obtaining a wide measuring range. This provides systematic theoretical backing for the advancement of the sensor, which has potential applications in the industrial detection of various ranges and complicated objects.

Chemoselectivity of the CuAAC/Ring Cleavage/Cyclization Reaction between Enaminones and α-Acylketenimine.

Ketenimines represent an important class of reactive species, useful synthetic intermediates, and synthons. However, in general, ketenimines preferentially undergoes nucleophilic addition reactions with hydroxyl and amino groups, and carbon functional groups remain a less studied subset of such systems. Herein, we develop a straightforward syntheses of pyridin-4(1H)-imines that is achieved by cyclization of a reacting enaminone unit with α-acylketenimine which is generated from the reactions of sulfonyl azides and terminal ynones in situ (CuAAC/Ring cleavage reaction). The cascade process preferentially starts with the nucleophilic α-C of the enaminone unit instead of an amino group, attacking the electron-deficient central carbon of ketenimine, and the chemoselectivity unconventional products pyridin-4(1H)-imines were formed by intramolecular cyclization.

Phase-Engineered WS2 Monolayer Quantum Dots by Rhenium Doping.

Transition metal dichalcogenides (TMDs) occur in the thermodynamically stable trigonal prismatic (2H) phase or the metastable octahedral (1T) phase. Phase engineering of TMDs has proven to be a powerful tool for applications in energy storage devices as well as in electrocatalysis. However, the mechanism of the phase transition in TMDs and the synthesis of phase-controlled TMDs remain challenging. Here we report the synthesis of Re-doped WS2 monolayer quantum dots (MQDs) using a simple colloidal chemical process. We find that the incorporation of a small amount of electron-rich Re atoms in WS2 changes the metal-metal distance in the 2H phase initially, which introduces strain in the structure (strained 2H (S2H) phase). Increasing the concentration of Re atoms sequentially transforms the S2H phase into the 1T and 1T' phases to release the strain. In addition, we performed controlled experiments by doping MoS2 with Re to distinguish between Re and Mo atoms in scanning transmission electron microscopy images and quantified the concentration range of Re atoms in each phase of MoS2, indicating that phase engineering of WS2 or MoS2 is possible by doping with different amounts of Re atoms. We demonstrate that the 1T' WS2 MQDs with 49 at. % Re show superior catalytic performance (a low Tafel slope of 44 mV/dec, a low overpotential of 158 mV at a current density of 10 mA/cm2, and long-term durability up to 5000 cycles) for the hydrogen evolution reaction. Our findings provide understanding and control of the phase transitions in TMDs, which will allow for the efficient manufacturing and translation of phase-engineered TMDs.

Enhancing the Performance of the p-n Heterostructure Electrolyte for Solid Oxide Fuel Cells via A-Site-Deficiency Engineering.

Semiconductor ionic electrolytes are attracting growing interest for developing low-temperature solid oxide fuel cells (LT-SOFCs). Our recent study has proposed a p-n heterostructure electrolyte based on perovskite oxide BaCo0.4Fe0.4Zr0.1Y0.1O3-δ (BCFZY) and ZnO, achieving promising fuel cell performance. Herein, to further improve the performance of the heterostructure electrolyte, an A-site-deficiency strategy is used to solely modify BCFZY for regulating the ionic conduction and catalytic activity of the heterostructure. Two new electrolytes, B0.9CFZY-ZnO and B0.8CFZY-ZnO, were developed and systematically studied. The results show that the two samples gain improved ionic conductivity and auxiliary catalytic activity after A-site deficiency as a result of the increment of the surface and interface oxygen vacancies. The single cells with B0.9CFZY-ZnO and B0.8CFZY-ZnO exhibit enhanced peak power outputs at 450-550 °C compared to the cell based on B1.0CFZY-ZnO (typically, 745 and 795 vs 542 mW cm-2 at 550 °C). Particular attention is paid to the impact of A-site deficiency on the interface energy band alignment between BxCFZY and ZnO, which suggests that the p-n heterojunction effect of BxCFZY-ZnO for charge carrier regulation can be tuned by A-site deficiency to enable high proton transport while avoiding fuel cell current leakage. This study thus confirms the feasibility of A-site-deficiency engineering to optimize the performance of the heterostructure electrolyte for developing LT-SOFCs.

Emerging nanotherapeutic strategies targeting gut-X axis against diseases.

Gut microbiota can coordinate with different tissues and organs to maintain human health, which derives the concept of the gut-X axis. Conversely, the dysbiosis of gut microbiota leads to the occurrence and development of various diseases, such as neurological diseases, liver diseases, and even cancers. Therefore, the modulation of gut microbiota offers new opportunities in the field of medicines. Antibiotics, probiotics or other treatments might restore unbalanced gut microbiota, which effects do not match what people have expected. Recently, nanomedicines with the high targeting ability and reduced toxicity make them an appreciative choice for relieving disease through targeting gut-X axis. Considering this paradigm-setting trend, the current review summarizes the advancements in gut microbiota and its related nanomedicines. Specifically, this article introduces the immunological effects of gut microbiota, summarizes the gut-X axis-associated diseases, and highlights the nanotherapeutics-mediated treatment via remolding the gut-X axis. Moreover, this review also discusses the challenges in studies related to nanomedicines targeting the gut microbiota and offers the future perspective, thereby aiming at charting a course toward clinic.

Targeting cullin neddylation for cancer and fibrotic diseases.

Protein neddylation is a post-translational modification, and its best recognized substrates are cullin family proteins, which are the core component of Cullin-RING ligases (CRLs). Given that most neddylation pathway proteins are overactivated in different cancers and fibrotic diseases, targeting neddylation becomes an emerging approach for the treatment of these diseases. To date, numerous neddylation inhibitors have been developed, of which MLN4924 has entered phase I/II/III clinical trials for cancer treatment, such as acute myeloid leukemia, melanoma, lymphoma and solid tumors. Here, we systematically describe the structures and biological functions of the critical enzymes in neddylation, highlight the medicinal chemistry advances in the development of neddylation inhibitors and propose the perspectives concerning targeting neddylation for cancer and fibrotic diseases.