Tanshinone analog inhibits castration-resistant prostate cancer cell growth by inhibiting glycolysis in an AR-dependent manner.

Androgen receptor (AR) is one of the key targets for the treatment of castration-resistant prostate cancer (CRPC). Current endocrine therapy can greatly improve patients with CRPC. However, with the change of pathogenic mechanism, acquired resistance often leads to the failure of treatment. Studies have shown that tanshinone IIA (TS-IIA) and its derivatives have significant antitumor activity, and have certain AR-targeting effects, but the mechanism is unknown. In this study, the TS-IIA analog TB3 was found to significantly inhibit the growth of CRPC in vitro and in vivo. Molecular docking, cellular thermal shift assay, and cycloheximide experiments confirmed that AR was the target of TB3 and promoted the degradation of AR. Furthermore, TB3 can significantly inhibit glycolysis metabolism by targeting the AR/PKM2 axis. The addition of pyruvic acid could significantly alleviate the inhibitory effect of TB3 on CRPC cells. Besides, the knockdown of AR or PKM2 also could reverse the effect of TB3 on CRPC cells. Taken together, our study suggests that TS-IIA derivative TB3 inhibits glycolysis to prevent the CRPC process by targeting the AR/PKM2 axis.

Carbon-Extraction-Induced Biaxial Strain Tuning of Carbon-Intercalated Iridium Metallene for Hydrogen Evolution Catalysis.

Metallene materials with atomic thicknesses are receiving increasing attention in electrocatalysis due to ultrahigh surface areas and distinctive surface strain. However, the continuous strain regulation of metallene remains a grand challenge. Herein, taking advantage of autocatalytic reduction of Cu2+ on biaxially strained, carbon-intercalated Ir metallene, we achieve control over the carbon extraction kinetics, enabling fine regulation of carbon intercalation concentration and continuous tuning of (111) in-plane (-2.0%-2.6%) and interplanar (3.5%-8.8%) strains over unprecedentedly wide ranges. Electrocatalysis measurements reveal the strain-dependent activity toward hydrogen evolution reaction (HER), where weakly strained Ir metallene (w-Ir metallene) with the smallest lattice constant presents the highest mass activity of 2.89 A mg-1Ir at -0.02 V vs reversible hydrogen electrode (RHE). Theoretical calculations validated the pivotal role of lattice compression in optimizing H binding on carbon-intercalated Ir metallene surfaces by downshifting the d-band center, further highlighting the significance of strain engineering for boosted electrocatalysis.

Atomic-Layer IrOx Enabling Ligand Effect Boosts Water Oxidation Electrocatalysis.

An in situ formed IrOx (x ≤ 2) layer driven by anodic bias serves as the essential active site of Ir-based materials for oxygen evolution reaction (OER) electrocatalysis. Once being confined to atomic thickness, such an IrOx layer possesses both a favorable ligand effect and maximized active Ir sites with a lower O-coordination number. However, limited by a poor understanding of surface reconstruction dynamics, obtaining atomic layers of IrOx remains experimentally challenging. Herein, we report an idea of material design using intermetallic IrVMn nanoparticles to induce in situ formation of an ultrathin IrOx layer (O-IrVMn/IrOx) to enable the ligand effect for achieving superior OER electrocatalysis. Theoretical calculations predict that a strong electronic interaction originating from an orderly atomic arrangement can effectively hamper the excessive leaching of transition metals, minimizing vacancies for oxygen coordination. Linear X-ray absorption near edge spectra analysis, extended X-ray absorption fine structure fitting outcomes, and X-ray photoelectron spectroscopy collectively confirm that Ir is present in lower oxidation states in O-IrVMn/IrOx due to the presence of unsaturated O-coordination. Consequently, the O-IrVMn/IrOx delivers excellent acidic OER performances with an overpotential of only 279 mV at 10 mA cm-2 and a high mass activity of 2.3 A mg-1 at 1.53 V (vs RHE), exceeding most Ir-based catalysts reported. Moreover, O-IrVMn/IrOx also showed excellent catalytic stability with only 0.05 at. % Ir dissolution under electrochemical oxidation, much lower than that of disordered D-IrVMn/IrOx (0.20 at. %). Density functional theory calculations unravel that the intensified ligand effect optimizes the adsorption energies of multiple intermediates involved in the OER and stabilizes the as-formed catalytic IrOx layer.

Di-n-butyl phthalate induces toxicity in male fetal mouse testicular development by regulating the MAPK signaling pathway.

"White pollution" has a significant impact on male reproduction. Di-n-butyl phthalate (DBP) is one of the most important factors in this type of pollution. Currently, research from international sources has demonstrated the significant reproductive toxicity of DBP. However, most of these studies have focused mainly on hormones expression at the protein and mRNA levels and the specific molecular targets of DBP and its mechanisms of action remain unclear. In this study, we established a Sprague Dawley pregnant mouse model exposed to DBP, and all male offspring were immediately euthanized at birth and bilateral testes were collected. We found through transcriptome sequencing that cell apoptosis and MAPK signaling pathway are the main potential pathways for DBP induced reproductive toxicity. Molecular biology analyses revealed a significant increase in the protein levels of JNK1(MAPK8) and BAX, as well as a significant increase in the BAX/BCL2 ratio after DBP exposure. Therefore, we propose that DBP induces reproductive toxicity by regulating JNK1 expression to activate the MAPK signaling pathway and induce reproductive cell apoptosis. In conclusion, our study provides the first evidence that the MAPK signaling pathway is involved in DBP-induced reproductive toxicity and highlights the importance of JNK1 as a potential target of DBP in inducing reproductive toxicity.

Design, synthesis and antitumor activity of 2-substituted quinazoline-4-amine derivatives.

Werner (WRN) syndrome protein is a multifunctional enzyme with helicase, ATPase, and exonuclease activities that are necessary for numerous DNA-related transactions in the human cell. Recent studies identified WRN as a synthetic lethal target in cancers. In this study, a series of new N-arylquinazoline-4-amine analogs were designed and synthesized based on structure optimization of quinazoline. The structures of the thirty-two newly synthesized compounds were confirmed by 1H NMR, 13C NMR and ESI-MS. The anticancer activity in vitro against chronic myeloid leukemia cells (K562), non-small cell lung cancer cells (A549), human prostate cancer cells (PC3), and cervical cancer cells (HeLa) of the target compounds was evaluated. Among them, the inhibition ratio of compounds 17d, 18a, 18b, 11 and 23a against four cancer cells at 5 µM concentration were more than 50 %. The IC50 values of compounds 18a and 18b were 0.3 ± 0.01 µM and 0.05 ± 0.02 µM in K562 cells respectively, compared with HeLa and A549 cells, 18a and 18b were more sensitive to K562 cells. In addition, the PC3 cells with WRN overexpression (PC3-WRN) was constructed, 18a and 18b and 23a were more sensitive to PC3-WRN cells compared with the control group cells (PC3-NC). Then, the cell viability of the novel WRN inhibitors were further assessed by colony formation assay. Compared with PC3-NC cells, 18b and 23a had obvious inhibitory effect on PC3-WRN cell at 1000 nM. In summary, these results indicated that the compounds 18b and 23a could be WRN protein inhibitor with potent anticancer properties in vitro.

A comparison of the postoperative outcomes between intraoperative leak testing and no intraoperative leak testing for gastric cancer surgery: a systematic review and meta-analysis.

BACKGROUND: Postoperative anastomotic leakage (PAL) is a serious complication of gastric cancer surgery. Although perioperative management has made considerable progress, anastomotic leakage (AL) cannot always be avoided. The purpose of this study is to evaluate whether intraoperative leak testing (IOLT) can reduce the incidence of PAL and other postoperative outcomes in gastric cancer surgery. MATERIALS AND METHODS: In this meta-analysis, we searched the PubMed, Embase, and Cochrane Library databases for clinical trials to assess the application of IOLT in gastric cancer surgery. All patients underwent laparoscopic radical gastrectomy for gastric cancer surgery. Studies comparing the postoperative outcomes of IOLT and no intraoperative leak testing (NIOLT) were included. Quality assessment, heterogeneity, risk of bias, and the level of evidence of the included studies were evaluated. PAL, anastomotic-related complications, 30-day mortality, and reoperation rates were compared between the IOLT and NIOLT group. RESULTS: Our literature search returned 721 results, from which six trials (a total of 1,666 patients) were included in our meta-analysis. Statistical heterogeneity was low. The primary outcome was PAL. IOLT reduced the incidence of PAL [2.09% vs 6.68%; (RR = 0.31, 95% Cl 0.19-0.53, P < 0.0001]. Anastomotic-related complications, which included bleeding, leakage, and stricture, were significantly higher in the NIOLT group than in the IOLT group [3.24% VS 10.85%; RR = 0.30, 95% Cl 0.18-0.53, P < 0.0001]. Moreover, IOLT was associated with lower reoperation rates [0.94% vs 6.83%; RR = 0.18, 95% CI 0.07-0.43, P = 0.0002]. CONCLUSION: Considering the observed lower incidence of postoperative anastomotic leakage (PAL), anastomotic-related complications, and reoperation rates, IOLT appears to be a promising option for gastric cancer surgery. It warrants further study before potential inclusion in future clinical guidelines.

Discovery of novel 4-trifluoromethyl-2-anilinoquinoline derivatives as potential anti-cancer agents targeting SGK1.

Given the critical necessity for the development of more potent anti-cancer drugs, a series of novel compounds incorporating trifluoromethyl groups within the privileged 2-anilinoquinoline scaffold was designed, synthesized, and subjected to biological evaluation through a pharmacophore hybridization strategy. Upon evaluating the in vitro anti-cancer characteristics of the target compounds, it became clear that compound 8b, which contains a (4-(piperazin-1-yl)phenyl)amino substitution at the 2-position of the quinoline skeleton, displayed superior efficacy against four cancer cell lines by inducing apoptosis and cell cycle arrest. Following research conducted in a PC3 xenograft mouse model, it was found that compound 8b exhibited significant anti-cancer efficacy while demonstrating minimal toxicity. Additionally, the analysis of a 217-kinase panel pinpointed SGK1 as a potential target for this compound class with anti-cancer capabilities. This finding was further verified through molecular docking analysis and cellular thermal shift assays. To conclude, our results emphasize that compound 8b can be used as a lead compound for the development of anti-cancer drugs that target SGK1.

Design and synthesis of N-aryl-2-trifluoromethyl-quinazoline-4-amine derivatives as potential Werner-dependent antiproliferative agents.

To discover new Werner (WRN) helicase inhibitors, a series of N-aryl-2-trifluoromethyl-quinazoline-4-amine derivatives were designed and synthesized through a structural optimization strategy, and the anticancer activities of 25 new target compounds against PC3, K562, and HeLa cell lines were evaluated by the MTT assay. Some of these compounds exhibited excellent inhibitory activity against three different cancer cell lines. Compounds 6a, 8i, and 13a showed better antiproliferative activity against K562 cells, with IC50 values of 3871.5, 613.6 and 134.7 nM, respectively, than did paclitaxel (35.6 nM), doxorubicin (2689.0 nM), and NSC 617145 (20.3 nM). To further verify whether the antiproliferative activity of these compounds is dependent on WRN, PC3 cells overexpressing WRN (PC3-WRN) were constructed to further study their antiproliferative potency in vitro, and the inhibition ratio and IC20 values showed that compounds 6a, 8i, and 13a were more sensitive to PC3-WRN than were the control group cells (PC3-NC). The IC20 ratios of compounds 6a, 8i, and 13a to PC3-NC and PC3-WRN were 94.3, 153.4 and 505.5, respectively. According to the docking results, the compounds 6a, 8i, and 13a overlapped well with the binding pocket of 6YHR. Further study demonstrated that among the tested compounds, 13a was the most sensitive to PC3-WRN. In summary, our research identified a series of N-aryl-2-trifluoromethyl-quinazoline-4-amine derivatives as potential WRN-dependent anticancer agents.

Design, Synthesis, and Biological Evaluation of Novel Quinazoline Derivatives Possessing a Trifluoromethyl Moiety as Potential Antitumor Agents.

A novel series of trifluoromethyl-containing quinazoline derivatives with a variety of functional groups was designed, synthesized, and tested for their antitumor activity by following a pharmacophore hybridization strategy. Most of the 20 compounds displayed moderate to excellent antiproliferative activity against five different cell lines (PC3, LNCaP, K562, HeLa, and A549). After three rounds of screening and structural optimization, compound 10 b was identified as the most potent one, with IC50 values of 3.02, 3.45, and 3.98 µM against PC3, LNCaP, and K562 cells, respectively, which were comparable to the effect of the positive control gefitinib. To further explore the mechanism of action of 10 b against cancer, experiments focusing on apoptosis induction, cell cycle arrest, and cell migration assay were conducted. The results showed that 10 b was able to induce apoptosis and prevent tumor cell migration, but had no effect on the cell cycle of tumor cells.

Integrated Wearable System for Monitoring Skeletal Muscle Force of Lower Extremities.

Continuous monitoring of lower extremity muscles is necessary, as the muscles support many human daily activities, such as maintaining balance, standing, walking, running, and jumping. However, conventional electromyography and physiological cross-sectional area methods inherently encounter obstacles when acquiring precise and real-time data pertaining to human bodies, with a notable lack of consideration for user comfort. Benefitting from the fast development of various fabric-based sensors, this paper addresses these current issues by designing an integrated smart compression stocking system, which includes compression garments, fabric-embedded capacitive pressure sensors, an edge control unit, a user mobile application, and cloud backend. The pipeline architecture design and component selection are discussed in detail to illustrate a comprehensive user-centered STIMES design. Twelve healthy young individuals were recruited for clinical experiments to perform maximum voluntary isometric ankle plantarflexion contractions. All data were simultaneously collected through the integrated smart compression stocking system and a muscle force measurement system (Humac NORM, software version HUMAC2015). The obtained correlation coefficients above 0.92 indicated high linear relationships between the muscle torque and the proposed system readout. Two-way ANOVA analysis further stressed that different ankle angles (p = 0.055) had more important effects on the results than different subjects (p = 0.290). Hence, the integrated smart compression stocking system can be used to monitor the muscle force of the lower extremities in isometric mode.

ß-C-H Allylation of Trialkylamines with Allenes Promoted by Synergistic Borane/Palladium Catalysis.

Functionalization of the C(sp3 )-H bonds of trialkylamines is challenging, especially for reactions at positions other than the α position. Herein, we report a method for ß-C(sp3 )-H allylation of trialkylamines. In these reactions, which involve synergistic borane/palladium catalysis, an enamine intermediate is first generated from the amine via α,ß-dehydrogenation promoted by B(C6 F5 )3 and a base, and then the enamine undergoes palladium-catalyzed reaction with an allene to give the allylation product. Because the hydride and the proton resulting from the initial dehydrogenation are ultimately shuttled to the product by B(C6 F5 )3 and the palladium catalyst, respectively, these reactions show excellent atom economy. The establishment of this method paves the way for future studies of C-H functionalization of trialkylamines by means of synergistic borane/transition-metal catalysis.

Single-Atom Cr-N4 Sites with High Oxophilicity Interfaced with Pt Atomic Clusters for Practical Alkaline Hydrogen Evolution Catalysis.

Although dispersing Pt atomic clusters (ACs) on a conducting support is a promising way to minimize the Pt amount required in hydrogen evolution reaction (HER), the catalytic mass activity and durability of Pt ACs are often unsatisfactory for alkaline HER due to their unfavorable water dissociation and challenges in stabilizing them against agglomeration and detachment. Herein, we report a class of single-atom Cr-N4 sites with high oxophilicity interfaced with Pt ACs on mesoporous carbon for achieving a highly active and stable alkaline HER in an anion-exchange-membrane water electrolyzer (AEMWE). The as-made catalyst achieves the highest reported Pt mass activity (37.6 times higher than commercial Pt/C) and outstanding operational stability. Experimental and theoretical studies elucidate that the formation of a unique Pt-Cr quasi-covalent bonding interaction at the interface of Cr-N4 sites and Pt ACs effectively suppresses the migration and thermal vibration of Pt atoms to stabilize Pt ACs and contributes to the greatly enhanced catalytic stability. Moreover, oxophilic Cr-N4 sites adjacent to Pt ACs with favorable adsorption of hydroxyl species facilitate nearly barrierless water dissociation and thus enhance the HER activity. An AEMWE using this catalyst (with only 50 µgPt cm-2) can operate stably at an industrial-level current density of 500 mA cm-2 at 1.8 V for >100 h with a small degradation rate of 90 µV h-1.

Design, synthesis and mechanism studies of dual EZH2/BRD4 inhibitors for cancer therapy.

Aberrant expression of EZH2 is frequently observed in cancers, and the EZH2 inhibitors are only effective in hematological malignancies and almost noneffective against solid tumors. It has been reported that the combination of EZH2 and BRD4 inhibitors may be a promising strategy to treat solid tumors being insensitive to EZH2 inhibitors. Thus, a series of EZH2/BRD4 dual inhibitors were designed and synthesized. The optimized compound 28, encoded as KWCX-28, was the most potential compound by the SAR studies. Further mechanism studies showed that KWCX-28 inhibited HCT-116 cells proliferation (IC50 = 1.86 µM), induced HCT-116 cells apoptosis, arrested cell cycle arrest at G0/G1 phase and resisted the histone 3 lysine 27 acetylation (H3K27ac) upregulation. Therefore, KWCX-28 was a potential dual EZH2/BRD4 inhibitors for treating solid tumors.

Biomimetic Robust All-Polymer Porous Coatings for Passive Daytime Radiative Cooling.

Passive daytime radiation cooling (PDRC) has gained considerable attention as an emerging and promising cooling technology. Polymer-based porous materials are one of the important candidates for PDRC application due to their easy processing, free of inorganic particle doping, and multifunctionality. However, the mechanical properties of these porous materials, which are critical in outdoor services, have been overlooked in previous studies. Herein, a nonsolvent-induced phase separation (NIPS) method combined with ambient pressure drying to prepare polyethylene-polysilicate all-polymer porous coatings is developed. The coatings possess a Cyphochilus beetle-like skeleton structure with optimal skeleton size, laminated anisotropy, and high volume fraction (64 ± 1%). These structure features ensure a maximum skeleton density without optical crowding, thus enhancing light scattering and stress dispersion, and balancing optical and mechanical properties. The coatings exhibit significant mechanical robustness (only ≈70 µm thickness reduction after 1000 Taber abrasion cycles at a 750 g load without influencing optical performance), durability, optical properties (a solar reflectance of ≈95% and an average near-normal thermal emittance of ≈96%), and PDRC performance (realizing sub-ambient cooling of ≈3-6 °C at midday with different weather conditions). The work provides a new solution to improve the practicability of polymer-based porous coatings in PDRC outdoor services and other fields.

Cannabinoids inhibit ethanol-induced activation of liver toxicity in rats through JNK/ERK/MAPK signaling pathways.

Cannabinoids (CBs) are psychoactive compounds, with reported anticancer, anti-inflammatory, and anti-neoplastic properties. The study was aimed at assessing the hepatoprotective effects of CB against ethanol (EtOH)-induced liver toxicity in rats. The animals were divided into seven groups: control (Group I) and Group II were treated with 50% ethanol (EtOH 5 mg/kg). Groups III, IV, and VI were treated with (EtOH + CB 10 mg/kg), (EtOH + CB 20 mg/kg), and (EtOH + CB 30 mg/kg), respectively. Groups V and VII consisted of animals treated with 20 and 30 mg/kg, of CB, respectively. Biochemical analysis revealed that Group IV (EtOH + CB 20 mg/kg) had reduced levels of ALT-alanine transferase, AST-aspartate aminotransferase, ALP-alanine peroxidase, MDA-malondialdehyde and increased levels of GSH-reduced glutathione. Histopathological analysis of liver and kidney tissues showed that EtOH + CB (20 and 30 mg/kg) treated animal groups exhibited normal tissue architecture similar to that of the control group. ELISA revealed that the inflammatory markers were reduced in the animal groups that were treated with EtOH + CB 20 mg/kg, in comparison to the animals treated only with EtOH. The mRNA expression levels of COX-2, CD-14, and MIP-2 showed a remarkable decrease in EtOH + CB treated animal groups to control groups. Western blot analysis revealed that CB downregulated p38/JNK/ERK thereby exhibiting its hepatoprotective property by inhibiting mitogen-activated protein kinase pathways. Thus, our findings suggest that CB is a potential candidate for the treatment of alcohol-induced hepatotoxicity.

Discovery of dual PARP and CDK6 inhibitors for triple-negative breast cancer with wild-type BRCA.

Inhibition of PARP is synthetic lethal with defects in BRCA, which provide effective targeted therapy strategy for BRCA mutation type of TNBC patients. However, approximately 80% of TNBC patients do not have BRCA mutations. Recent studies have shown that CDK4/6 inhibitors can increase the sensitivity of wild-type BRCA cells to PARP inhibitors. We designed a series of dual PARP and CDK6 inhibitors, and the most promising compound, P4i, showed good inhibitory activity against PARP1 and CDK6 and good inhibitory effects on MDA-MB-231 (IC50 = 1.96 µM), MDA-MB-468 (IC50 = 2.81 µM) and BT-549 (IC50 = 2.37 µM) cells with wild-type BRCA. Compared with Olaparib, the inhibition capacity of the three BRCA wild-type (MDA-MB-231, MDA-MB-468 and BT-549) cells was about 10-20 times higher, and even better than the combination of Olaparib and Palbociclib. As a novel PARP multifunctional molecule, it is a potential compound for the treatment of BRCA wild-type TNBC.

Discovery of novel 2-(trifluoromethyl)quinolin-4-amine derivatives as potent antitumor agents with microtubule polymerization inhibitory activity.

In this work, a series of 2-(trifluoromethyl)quinolin-4-amine derivatives were designed and synthesized through structural optimization strategy as a microtubule-targeted agents (MTAs) and their cytotoxicity activity against PC3, K562 and HeLa cell lines were evaluated. The half maximal inhibitory concentration (IC50) of 5e, 5f, and 5o suggested that their potency of anti-proliferative activities against HeLa cell lines were better than the combretastatin A-4. Compound 5e showed the higher anti-proliferative activity against PC3, K562 and HeLa in vitro with IC50 values of 0.49 µM, 0.08 µM and 0.01 µM, respectively. Further mechanism study indicated that the representative compound 5e was new class of tubulin inhibitors by EBI competition assay and tubulin polymerization assays, it is similar to colchicine. Immunofluorescence staining revealed that compound 5e apparently disrupted tubulin network in HeLa cells, and compound 5e arrested HeLa cells at the G2/M phase and induced cells apoptosis in a dose-dependent manner. Molecular docking results illustrated that the hydrogen bonds of represented compounds reinforced the interactions in the pocket of colchicine binding site. Preliminary results suggested that 5e deserves further research as a promising tubulin inhibitor for the development of anticancer agents.

Efficacy and safety of anastomotic leak testing in gastric cancer: a randomized controlled trial.

BACKGROUND: Anastomosis-related complications such as bleeding, leakage, and strictures, continue to be serious complications of gastric cancer surgery. Presently, these complications have yet to be reliably prevented. Here we design a comprehensive leak testing procedure which combines gastroscopy, air, and methylene blue (GAM) leak testing. We aimed to evaluated the efficacy and safety of the GAM procedure in patients with gastric cancer. METHODS: Patients aged 18-85 years without an unresectable factor as confirmed via CT were enrolled in a prospective randomized clinical trial at a tertiary referral teaching hospital and were randomly assigned to two groups: intraoperative leak testing group (IOLT) and no intraoperative leak testing group (NIOLT). The primary endpoint was the incidence of postoperative anastomosis-related complications in the two groups. RESULTS: 148 patients were initially randomly assigned to the IOLT group (n = 74) and to the NIOLT group (n = 74) between September 2018 and September 2022. After exclusions, 70 remained in the IOLT group and 68 in the NIOLT group. In the IOLT group, 5 patients (7.1%) were found to have anastomotic defects intraoperatively, which included anastomotic discontinuity, bleeding, and strictures. The NIOLT group had a higher incidence of postoperative anastomotic leakage compared to the IOLT group: 4 patients (5.8%) vs 0 patients (0%), respectively. No GAM-related complications were observed. CONCLUSION: The GAM procedure is an intraoperative leak test that can be performed safely and efficiently after a laparoscopic total gastrectomy. GAM anastomotic leak testing may effectively prevent technical defect-related anastomotic complications in patients with gastric cancer who undergo a gastrectomy. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT04292496.

Research Progress on the Anticancer Molecular Mechanism of Targets Regulating Cell Autophagy.

BACKGROUND: Autophagy is a lysosome-mediated catabolic process that maintains cell homeostasis and survival. It occurs not only in normal cells such as cardiac muscle cells, neurons, and pancreatic acinar cells but also in various benign and malignant tumors. The abnormal level of intracellular autophagy is closely related to multiple pathophysiological processes, including aging, neurodegeneration, infectious diseases, immune disorders, and cancer. Autophagy mainly plays a dual role in life and death by regulating cell survival, proliferation, and death, thus being involved in the occurrence, development, and treatment of cancer. It is also involved in chemotherapy resistance by a dual role, since it not only promotes the occurrence of drug resistance but also reverses it. Previous findings suggest that the regulation of autophagy can be used as an effective strategy in tumor therapy. SUMMARY: Recent studies found that small molecules from natural products and their derivatives exert anticancer activity by regulating the level of autophagy in tumor cells. KEY MESSAGES: Therefore, this review article describes the mechanism of autophagy, the role of autophagy in normal cells and tumor cells, and the research progress on the anticancer molecular mechanism of targets regulating cell autophagy. The aim is to provide a theoretical basis for developing autophagy inhibitors or activators to improve anticancer efficacy.

Additional diagnostic value of CNV-seq over conventional karyotyping in prenatal diagnosis: A systematic review and meta-analysis.

OBJECTIVE: To identify the additional diagnostic value of CNV-seq over conventional karyotyping on the part of chromosomal abnormalities in prenatal diagnosis. METHOD: This was a systematic review conducted in accordance with PRISMA criteria. In order to clarify related research, PubMed, Web of Science databases (including Core Collection, BIOSIS Previews, MEDLINE, and so on), The Cochrane Library and Wiley Online Library were searched with the terms: "prenatal diagnosis," "CNV-seq," "karyotyping," published from January 2010 to May 2022. No language restrictions. RenMan 5.4 was used for the meta-analysis. RESULTS: Eight studies were included in this systemic review and meta-analysis, including 11 091 pregnant women with high-risk pregnancy factors or with structurally abnormal fetus under ultrasound. CNV-seq detected a 2% (95% CI, -0% to 4%) additional chromosomal anomalies over conventional karyotyping in the six series. A 4% (95% CI, 3%-6%) pooled mean incremental yield of pathogenic CNVs by CNV-seq over karyotyping was observed, with a 1%-16% range. CONCLUSION: CNV-seq, applied in prenatal diagnosis, may detect more chromosomal abnormalities when compared with karyotyping. With the advantages of wide coverage, high throughput, high resolution, no culture, good compatibility, and adjustable sequencing depth, CNV-seq has high application value in prenatal diagnosis.