Improved photosynthetic performance under unilateral weak light conditions in a wide-narrow-row intercropping system is associated with altered sugar transport.

Intercropping improves resource utilization. Under wide-narrow-row maize (Zea mays) intercropping, maize plants are subjected to weak unilateral illumination and exhibit high photosynthetic performance. However, the mechanism regulating photosynthesis under unilateral weak light remains unknown. We investigated the relationship between photosynthesis and sugar metabolism in maize under unilateral weak light. Our results showed that the net photosynthetic rate (Pn) of unshaded leaves increased as the level of shade on the other side increased. On the contrary, the concentration of sucrose and starch and the number of starch granules in the unshaded leaves decreased with increased shading due to the transfer of abundant C into the grains. However, sink loss with ear removal reduced the Pn of unshaded leaves. Intense unilateral shade (40% to 20% normal light), but not mild unilateral shade (60% normal light), reduced grain yield (37.6% to 54.4%, respectively). We further found that in unshaded leaves, Agpsl, Bmy, and Mexl-like expression significantly influenced sucrose and starch metabolism, while Sweet13a and Sut1 expression was crucial for sugar export. In shaded leaves, expression of Sps1, Agpsl, and Sweet13c was crucial for sugar metabolism and export. This study confirmed that unshaded leaves transported photosynthates to the ear, leading to a decrease in sugar concentration. The improvement of photosynthetic performance was associated with altered sugar transport. We propose a narrow-row spacing of 40 cm, which provides appropriate unilateral shade and limits yield reduction.

Effect of breathing exercises on patients with interstitial lung disease: A systematic review and meta-analysis.

PURPOSE: This study was designed to synthesize the efficacy and safety of breathing exercises in interstitial lung disease (ILD) patients by reviewing the literature and comparing the impact of different control group types, ILD subtypes, breathing exercise action modes or methods, and intervention durations on clinical efficacy. METHODS: Systematic searches were conducted across 9 electronic databases, including PubMed, to retrieve English and Chinese studies reporting on ILD patients from inception to February 12, 2024. Study selection and data extraction were independently conducted by two researchers. The quality of the included studies was assessed using the Cochrane risk of bias tool. The data were analysed using RevMan 5.4 and STATA 17.0 software. RESULTS: The search identified 25 studies. Compared to the control group, the breathing exercise group exhibited significantly improved lung function (FVC%pred: MD = 3.46, 95%CI = 1.04 to 5.88; DLCO%pred: MD = 3.20, 95% CI = 2.91 to 3.48), dyspnoea (MRC or mMRC scale: MD = - 0.50, 95%CI = - 0.77 to - 0.22), exercise capacity (6MWD: MD = 32.65, 95% CI = 14.77 to 50.53), and HRQoL (SGRQ: MD = - 6.53, 95% CI = - 8.72 to - 4.34) in ILD patients. According to the subgroup analysis, significant improvements consistent with the overall results were observed in the control group with usual treatment. Compared with the control group, breathing exercises had varying degrees of improvement in the mixed diagnostic group, known-cause group, and fibrotic group of ILD patients; breathing exercises alone significantly improved DLCO%pred, MRC (or mMRC), and SGRQ; and the improvement in breathing exercises as part of pulmonary rehabilitation (PR) was more notable. Different durations of breathing exercise could promote the efficacy of different aspects of treatment for ILD patients. CONCLUSIONS: Compared with usual treatment, breathing exercises can improve lung function, exercise capacity, and HRQoL in ILD patients, particularly without high requirements for intervention duration. The efficacy of breathing exercises varies for different ILD subtypes, and incorporating breathing exercises as part of PR can be more beneficial for ILD patients. No studies have shown significant risks for ILD patients engaging in breathing exercises.

Particle size effect on surface/interfacial tension and Tolman length of nanomaterials: A simple experimental method combining with theoretical.

Surface tension and interfacial tension are crucial to the study of nanomaterials. Herein, we report a solubility method using magnesium oxide nanoparticles of different radii (1.8-105.0 nm, MgO NPs) dissolved in pure water as a targeted model; the surface tension and interfacial tension (and their temperature coefficients) were determined by measuring electrical conductivity and combined with the principle of the electrochemical equilibrium method, and the problem of particle size dependence is discussed. Encouragingly, this method can also be used to determine the ionic (atomic or molecular) radius and Tolman length of nanomaterials. This research results disclose that surface/interfacial tension and their temperature coefficients have a significant relationship with particle size. Surface/interfacial tension decreases rapidly with a radius <10 nm (while the temperature coefficients are opposite), while for a radius >10 nm, the effect is minimal. Especially, it is proven that the value of Tolman length is positive, the effect of particle size on Tolman length is consistent with the surface/interfacial tension, and the Tolman length of the bulk does not change much in the temperature range. This work initiates a new era for reliable determination of surface/interfacial tension, their temperature coefficients, ionic radius, and Tolman length of nanomaterials and provides an important theoretical basis for the development and application of various nanomaterials.

Liuwei Dihuang pills attenuate ovariectomy-induced bone loss by alleviating bone marrow mesenchymal stem cell (BMSC) senescence via the Yes-associated protein (YAP)-autophagy axis.

CONTEXT: Liuwei Dihuang pill (LWDH) has been used to treat postmenopausal osteoporosis (PMOP). OBJECTIVE: To explore the effects and mechanisms of action of LWDH in PMOP. MATERIALS AND METHODS: Forty-eight female Sprague-Dawley rats were divided into four groups: sham-operated (SHAM), ovariectomized (OVX), LWDH high dose (LWDH-H, 1.6 g/kg/d) and LWDH low dose (LWDH-L, 0.8 g/kg/d); the doses were administered after ovariectomy via gavage for eight weeks. After eight weeks, the bone microarchitecture was evaluated. The effect of LWDH on the differentiation of bone marrow mesenchymal stem cells (BMSCs) was assessed via osteogenesis- and lipogenesis-induced BMSC differentiation. The senescence-related biological indices were also detected using senescence staining, cell cycle analysis, quantitative real-time polymerase chain reaction and western blotting. Finally, the expression levels of autophagy-related proteins and Yes-associated protein (YAP) were evaluated. RESULTS: LWDH-L and LWDH-H significantly modified OVX-induced bone loss. LWDH promoted osteogenesis and inhibited adipogenesis in OVX-BMSCs. Additionally, LWDH decreased the positive ratio of senescence OVX-BMSCs and improved cell viability, cell cycle, and the mRNA and protein levels of p53 and p21. LWDH upregulated the expression of autophagy-related proteins, LC3, Beclin1 and YAP, in OVX-BMSCs and downregulated the expression of p62. DISCUSSION AND CONCLUSIONS: LWDH improves osteoporosis by delaying the BMSC senescence through the YAP-autophagy axis.

Extracellular vesicles derived from hypoxia-preconditioned bone marrow mesenchymal stem cells ameliorate lower limb ischemia by delivering miR-34c.

Hypoxic mesenchymal stem cell-derived extracellular vesicles (EVs) have been suggested as a promising therapy for various diseases. This study aims to determine the effect of EVs derived from bone marrow mesenchymal stem cells (BMMSCs) under hypoxia on lower limb ischemia and the underlying mechanism. Human BMMSCs were subjected to hypoxia or normoxia followed by the isolation of EVs. Nanoparticle trafficking analysis (NTA), transmission electron microscopy (TEM), and Western Blotting using corresponding markers were performed to confirm the EVs. The EVs from BMMSCs under hypoxia condition (Hyp-EVs) or normoxia condition (Nor-EVs) were subjected to hindlimb ischemia (HI) mice. MiR-34c expression in BMMSCs and BMMSC-EVs was detected. The role of miR-34c in regulating M2 macrophage polarization, as well as the target of miR-34c, were explored. HI mice with Hyp-EV treatment, as compared to the Nor-EV or the PBS group, had better blood flow and higher capillary density. MiR-34c expression was increased in BMMSCs, BMMSC-EVs, and the adductor muscle of HI mice. Hyp-EVs promoted the M2 macrophage polarization and anti-inflammatory cytokine production, and enhanced the blood flow and capillary density in HI mice, while the knockdown of miR-34c partly reversed these effects. PTEN is a target of miR-34c, and the PTEN silencing facilitated M2 macrophage polarization, whereas the inhibition of AKT signaling partly abolished the effect. Hyp-EVs promoted M2 macrophage polarization by delivering miR-34c via PTEN/AKT pathway, which could be a promising therapeutic strategy to ameliorate lower limb ischemia.

The potential role of N6-methyladenosine modification of LncRNAs in contributing to the pathogenesis of chronic glomerulonephritis.

BACKGROUND: Increasing evidence indicates that N6-methyladenosine (m6A) modification of mRNAs has been shown to play a critical role in the occurrence and development of many diseases, while little is known about m6A modification in long non-coding RNAs (LncRNAs). Our study aims to investigate the potential functions of LncRNA m6A modifications in lipopolysaccharide (LPS)-induced mouse mesangial cells (MMCs), providing us with a new perspective on the molecular mechanisms of chronic glomerulonephritis (CGN) pathogenesis. METHODS: Differentially methylated LncRNAs were identified by Methylated RNA immunoprecipitation sequencing (MeRIP-seq). LncRNA-mRNA and LncRNA-associated LncRNA-miRNA-mRNA (CeRNA) networks were constructed by bioinformatics analysis. Furthermore, we utilized gene ontology (GO) and pathway enrichment analyses (KEGG) to explore target genes from co-expression networks. In addition, the total level of m6A RNA methylation and expression of methyltransferase and pro-inflammatory cytokines were detected by the colorimetric quantification method and western blot, respectively. Cell viability and cell cycle stage were detected by cell counting kit-8 (CCK-8) and flow cytometry. RESULTS: In total, 1141 differentially m6A-methylated LncRNAs, including 529 hypermethylated LncRNAs and 612 hypomethylated LncRNAs, were determined by MeRIP-seq. The results of GO and KEGG analysis revealed that the target mRNAs were mainly enriched in signal pathways, such as the NF-kappa B signaling pathway, MAPK signaling pathway, Toll-like receptor signaling pathway, and apoptosis signaling pathway. In addition, higher METTL3 expression was found in CGN kidney tissues using the GEO database. METTL3 knockdown in MMC cells drastically reduced the levels of m6A RNA methylation, pro-inflammatory cytokines IL6 and TNF-α, and inhibited cell proliferation and cycle progression. CONCLUSIONS: Our findings provide a basis and novel insight for further investigations of m6A modifications in LncRNAs for the pathogenesis of CGN.

Exploring the alternative virulence determinants PB2 S155N and PA S49Y/D347G that promote mammalian adaptation of the H9N2 avian influenza virus in mice.

The occurrence of human infections caused by avian H9N2 influenza viruses has raised concerns regarding the potential for human epidemics and pandemics. The molecular basis of viral adaptation to a new host needs to be further studied. Here, the bases of nucleotides 627 and 701 of PB2 were changed according to the uncoverable purine-to-pyrimidine transversion to block the development of PB2 627K and 701N mutations during serial passaging in mice. The purpose of this experiment was to identify key adaptive mutations in polymerase and NP genes that were obscured by the widely known host range determinants PB2 627K and 701N. Mouse-adapted H9N2 variants were obtained via twelve serial lung-to-lung passages. Sequence analysis showed that the mouse-adapted viruses acquired several mutations within the seven gene segments (PB2, PB1, PA, NP, HA, NA, and NS). One variant isolate with the highest polymerase activity possessed three substitutions, PB2 S155N, PA S49Y and D347G, which contributed to the highly virulent and mouse-adaptative phenotype. Further studies demonstrated that these three mutations resulted in increased polymerase activity, viral transcription and replication in mammalian cells, severe interstitial pneumonia, excessive inflammatory cellular infiltration and increased growth rates in mice. Our results suggest that the substitution of these three amino acid mutations may be an alternative strategy for H9N2 avian influenza viruses to adapt to mammalian hosts. The continued surveillance of zoonotic H9N2 influenza viruses should also include these mammalian adaptation markers as part of our pandemic preparedness efforts.

A case report of long-delayed diagnosis of pseudorabies virus encephalitis with endophthalmitis: lessons from metagenomic next generation sequencing.

BACKGROUND: Pseudorabies virus (PRV) was thought to only infect animals. Recent studies have shown that it can also infect human. CASE PRESENTATION: We report a case of pseudorabies virus encephalitis and endophthalmitis, diagnosed 89 days after onset, confirmed with intraocular fluid metagenomic next generation sequencing (mNGS) after the result of two cerebrospinal fluid (CSF) mNGS tests were negative. Although treatment with intravenous acyclovir, foscarnet sodium, and methylprednisolone improved the symptoms of encephalitis, significant diagnostic delay resulted in permanent visual loss. CONCLUSIONS: This case suggests that pseudorabies virus (PRV) DNA in the intraocular fluid may have a higher positivity than that in the CSF. PRV may persist in the intraocular fluid for an extended period and may thus require extended antiviral therapy. Patients with severe encephalitis and PRV should be examined with the focus on pupil reactivity and light reflex. A fundus examination should be performed in patients with a central nervous system infection, specifically, those in a comatose state, to help reduce eye disability.

p53 downregulates PD-L1 expression via miR-34a to inhibit the growth of triple-negative breast cancer cells: a potential clinical immunotherapeutic target.

BACKGROUND: Compared with other breast cancer subtypes, triple-negative breast cancer (TNBC) has poorer responses to therapy and lower overall survival rates. The use of an inhibitor of immune checkpoint programmed cell death ligand 1 (PD-L1) is a promising treatment strategy and is approved for malignant tumors, especially for TNBC. p53 regulates various biological processes, but the association between p53 and immune evasion remains unknown. miR-34a is a known tumor suppressor and p53-regulated miRNA that is downregulated in several cancers; however, it has not been reported in TNBC. Herein, we aimed to explore the regulatory signaling axis among p53, miR-34a and PD-L1 in TNBC cells in vivo and in tissue and to improve our understanding of immunotherapy for TNBC. METHODS AND RESULTS: p53-EGFP, p53-siRNA and miR-34a mimics were transfected into TNBC cell lines, and the interaction between miR-34a and PD-L1 was analyzed via dual-luciferase reporter assays. We found that p53 could inhibit the expression of PD-L1 via miR-34a and that miR-34a could inhibit both cell activity and migration and promoted apoptosis and cytotoxicity in TNBC. Furthermore, miR-34a agomir was injected into MDA-MB-231 tumors of nude mice. The results showed that miR-34a could inhibit tumor growth and downregulate the expression of PD-L1 in vivo. A total of 133 TNBC tissue samples were analyzed by immunochemistry; the proportion of positive expression of PD-L1 was 57.14% (76/133), and the proportion of samples with negative expression of PD-L1 was 42.86% (57/133). CONCLUSION: Our research may provide a novel potential target for TNBC.

High antipersister activity of a promising new quinolone drug candidate in eradicating uropathogenic Escherichia coli persisters and persistent infection in mice.

AIMS: To develop more potent drugs that eradicate persister bacteria and cure persistent urinary tract infections (rUTIs). METHODS AND RESULTS: We synthesized eight novel clinifloxacin analogs and measured minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), the time-kill curves in uropathogenic Escherichia coli (UPEC) UTI89, and applied the candidate drugs and combinations against biofilm bacteria in vitro and in mice. Transcriptomic analysis was performed for UPEC after candidate drug treatment to shed light on potential mechanism of action. We identified Compound 2, named Qingdafloxacin (QDF), which was more potent than clinafloxacin and clinically used levofloxacin and moxifloxacin, with an MIC of < 0.04 µg ml-1 and an MBC of 0.08∼0.16 µg ml-1. In drug combination studies, QDF + gentamicin + nitrofuran combination but not single drugs completely eradicated all stationary phase bacteria containing persisters and biofilm bacteria, and all bacteria in a persistent UTI mouse model. Transcriptome analysis revealed that the unique antipersister activity of QDF was associated with downregulation of genes involved in bacterial stress response, DNA repair, protein misfolding repair, pyrimidine metabolism, glutamate, and glutathione metabolism, and efflux. CONCLUSIONS: QDF has high antipersister activity and its drug combinations proved highly effective against biofilm bacteria in vitro and persistent UTIs in mice, which may have implications for treating rUTIs.

Engineering a triple-functional magnetic gel driving mutually-synergistic mild hyperthermia-starvation therapy for osteosarcoma treatment and augmented bone regeneration.

Malignant bone tumors result in high rates of disability and death and are difficult to treat in terms of killing tumors and repairing bone defects. Compared with other hyperthermia strategies, magnetic hyperthermia has become an effective therapy for treating malignant bone tumors due to its lack of depth limitations. However, tumor cells express heat shock protein (HSP) to resist hyperthermia, which reduces its curative effect. Competitive ATP consumption can reduce HSP production; fortunately, the basic principle of starvation therapy by glucose oxidase (GOx) is consuming glucose to control ATP production, thereby restricting HSP generation. We developed a triple-functional magnetic gel (Fe3O4/GOx/MgCO3@PLGA) as a magnetic bone repair hydrogels (MBRs) with liquid‒solid phase transition capability to drive magneto-thermal effects to simultaneously trigger GOx release and inhibit ATP production, reducing HSP expression and thereby achieving synergistic therapy for osteosarcoma treatment. Moreover, magnetic hyperthermia improves the effect of starvation therapy on the hypoxic microenvironment and achieves a reciprocal strengthening therapeutic effect. We further demonstrated that in situ MBRs injection effectively suppressed tumor growth in 143B osteosarcoma tumor-bearing mice and an in-situ bone tumor model in the rabbit tibial plateau. More importantly, our study also showed that liquid MBRs could effectively match bone defects and accelerate their reconstruction via magnesium ion release and enhanced osteogenic differentiation to augment the regeneration of bone defects caused by bone tumors, which generates fresh insight into malignant bone tumor treatment and the acceleration of bone defect repair.

Marine Sulfated Polysaccharide PMGS Synergizes with Paclitaxel in Inhibiting Cervical Cancer In Vitro.

The incidence and mortality of cervical cancer in female malignancies are second only to breast cancer, which brings a heavy health and economic toll worldwide. Paclitaxel (PTX)-based regimens are the first-class choice; however, severe side effects, poor therapeutic effects, and difficulty in effectively preventing tumor recurrence or metastasis are unavoidable. Therefore, it is necessary to explore effective therapeutic interventions for cervical cancer. Our previous studies have shown that PMGS, a marine sulfated polysaccharide, exhibits promising anti-human papillomavirus (anti-HPV) effects through multiple molecular mechanisms. In this article, a continuous study identified that PMGS, as a novel sensitizer, combined with PTX exerted synergistic anti-tumor effects on cervical cancer associated with HPV in vitro. Both PMGS and PTX inhibited the proliferation of cervical cancer cells, and the combination of PMGS with PTX displayed significant synergistic effects on Hela cells. Mechanistically, PMGS synergizes with PTX by enhancing cytotoxicity, inducing cell apoptosis and inhibiting cell migration in Hela cells. Collectively, the combination of PTX and PMGS potentially provides a novel therapeutic strategy for cervical cancer.

High-Precision Carton Detection Based on Adaptive Image Augmentation for Unmanned Cargo Handling Tasks.

Unattended intelligent cargo handling is an important means to improve the efficiency and safety of port cargo trans-shipment, where high-precision carton detection is an unquestioned prerequisite. Therefore, this paper introduces an adaptive image augmentation method for high-precision carton detection. First, the imaging parameters of the images are clustered into various scenarios, and the imaging parameters and perspectives are adaptively adjusted to achieve the automatic augmenting and balancing of the carton dataset in each scenario, which reduces the interference of the scenarios on the carton detection precision. Then, the carton boundary features are extracted and stochastically sampled to synthesize new images, thus enhancing the detection performance of the trained model for dense cargo boundaries. Moreover, the weight function of the hyperparameters of the trained model is constructed to achieve their preferential crossover during genetic evolution to ensure the training efficiency of the augmented dataset. Finally, an intelligent cargo handling platform is developed and field experiments are conducted. The outcomes of the experiments reveal that the method attains a detection precision of 0.828. This technique significantly enhances the detection precision by 18.1% and 4.4% when compared to the baseline and other methods, which provides a reliable guarantee for intelligent cargo handling processes.

The research progress on the anxiolytic effect of plant-derived flavonoids by regulating neurotransmitters.

Phytopharmaceuticals have attracted a lot of attention due to their multicomponent and multiple targets. The natural phenolic chemicals known as flavonoids are found in a wide variety of plants, fruits, vegetables, and herbs. Recently, they have been found to have modulatory effects on anxiety disorders, with current research focusing on the modulation of neurotransmitters. There has not yet been a review of the various natural flavonoid monomer compounds and total plant flavonoids that have been found to have anxiolytic effects. The study on the anti-anxiety effects of plant-derived flavonoids on neurotransmitters was reviewed in this paper. We, therefore, anticipate that further study on the conformational interaction underlying flavonoids' anti-anxiety effects will offer a theoretical framework for the creation of pertinent treatments.

Potassium Dehydroandrograpolide Succinate Targets NRP1 Mediated VEGFR2/VE-Cadherin Signaling Pathway to Promote Endothelial Barrier Repair.

Impairment of vascular endothelial integrity is associated with various vascular diseases. Our previous studies demonstrated that andrographolide is critical to maintaining gastric vascular homeostasis, as well as to regulating pathological vascular remodeling. Potassium dehydroandrograpolide succinate (PDA), a derivative of andrographolide, has been clinically used for the therapeutic treatment of inflammatory diseases. This study aimed to determine whether PDA promotes endothelial barrier repair in pathological vascular remodeling. Partial ligation of the carotid artery in ApoE-/- mice was used to evaluate whether PDA can regulate pathological vascular remodeling. A flow cytometry assay, BRDU incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay and Matrigel-based tube formation assay were performed to determine whether PDA can regulate the proliferation and motility of HUVEC. A molecular docking simulation and CO-immunoprecipitation assay were performed to observe protein interactions. We observed that PDA induced pathological vascular remodeling characterized by enhanced neointima formation. PDA treatment significantly enhanced the proliferation and migration of vascular endothelial cells. Investigating the potential mechanisms and signaling pathways, we observed that PDA induced endothelial NRP1 expression and activated the VEGF signaling pathway. Knockdown of NRP1 using siRNA transfection attenuated PDA-induced VEGFR2 expression. The interaction between NRP1 and VEGFR2 caused VE-Cad-dependent endothelial barrier impairment, which was characterized by enhanced vascular inflammation. Our study demonstrated that PDA plays a critical role in promoting endothelial barrier repair in pathological vascular remodeling.

A Chinese Herb Prescription "Fang-gan Decoction" Protects Against Damage to Lung and Colon Epithelial Cells Caused by the SARS-CoV-2 Spike Protein by Regulating the TGF-ß/Smad2/3 and NF-κB Pathways.

Objective To explore the effects and mechanisms of a traditional Chinese medicine (TCM) prescription, "Fang-gan Decoction" (FGD), in protecting against SARS-CoV-2 spike protein-induced lung and intestinal injuries in vitro and in vivo.Methods Female BALB/c mice and three cell lines pretreated with FGD were stimulated with recombinant SARS-CoV-2 spike protein (spike protein). Hematoxylin-eosin (HE) staining and pathologic scoring of tissues, cell permeability and viability, and angiotensin-converting enzyme 2 (ACE2) expression in the lung and colon were detected. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of inflammatory factors in serum and cell supernatant. The expression of NF-κB p65, p-NF-κB p65, p-IκBα, p-Smad2/3, TGF-ß1, Caspase3, and Bcl-2 was evaluated by Western blotting.Results FGD protected against the damage to the lung and colon caused by the spike protein in vivo and in vitro according to the pathologic score and cell permeability and viability (P<0.05). FGD up-regulated ACE2 expression, which was reduced by the spike protein in the lung and colon, significantly improved the deregulation of inflammatory markers caused by the spike protein, and regulated the activity of TGF-ß/Smads and NF-κB signaling.Conclusion Traditional Chinese medicine has a protective effect on lung and intestinal tissue injury stimulated by the spike protein through possible regulatory functions of the NF-κB and TGF-ß1/Smad pathways with tissue type specificity.

Disruption of Zinc Homeostasis by a Novel Platinum(IV)-Terthiophene Complex for Antitumor Immunity.

Zinc homeostatic medicine is of great potential for cancer chemo-immunotherapy; however, there are few reports on antitumor compounds that can trigger Zn2+ -mediated immune responses. In this work, we developed a novel cyclometalated PtIV -terthiophene complex, Pt3, that not only induces DNA damage and cellular metabolism dysregulation, but also disrupts zinc homeostasis as indicated by the abnormal transcriptional level of zinc regulatory proteins, excess accumulation of Zn2+ in cytoplasm, and down-regulation of metallothioneins (MTs), which further caused redox imbalance. The simultaneous disruption of zinc and redox homeostasis in response to Pt3 treatment activated gasdermin-D mediated pyroptosis accompanied by cytoskeleton remodeling, thus releasing pro-inflammatory cytokines to promote dendritic cell (DC) maturation and T cell tumor-infiltration, eventually eliminating both primary and distant tumors in vivo. As far as we know, this is the first metal complex that can regulate zinc homeostasis to activate antitumor immunity.

A Golgi-Targeted Platinum Complex Plays a Dual Role in Autophagy Regulation for Highly Efficient Cancer Therapy.

Regulating autophagy to control the homeostatic recycling process of cancer cells is a promising anticancer strategy. Golgi apparatus is a substrate of autophagy but the Golgi-autophagy (Golgiphagy) mediated antitumor pathway is rarely reported. Herein, we have developed a novel Golgi-targeted platinum (II) complex Pt3, which is ca. 20 times more cytotoxic to lung carcinoma than cisplatin and can completely eliminate tumors after intratumoral administration in vivo. Its nano-encapsulated system for tail vein administration also features a good anti-tumor effect. Mechanism studies indicate that Pt3 induces substantial Golgi stress, indicated by the fragmentation of Golgi structure, down-regulation of Golgi proteins (GM130, GRASP65/55), loss of Golgi-dependent transport and glycosylation. This triggers Golgiphagy but blocks the subsequent fusion of autophagosomes with lysosomes, that is a dual role in autophagy regulation, resulting in loss of proteostasis and apoptotic cell death. As far as we know, Pt3 is the first Golgi-targeted Pt complex that can trigger Golgi stress-mediated dual-regulation of autophagic flux and autophagy-apoptosis crosstalk for highly efficient cancer therapy.

Small protein complex prediction algorithm based on protein-protein interaction network segmentation.

BACKGROUND: Identifying protein complexes from protein-protein interaction network is one of significant tasks in the postgenome era. Protein complexes, none of which exceeds 10 in size play an irreplaceable role in life activities and are also a hotspot of scientific research, such as PSD-95, CD44, PKM2 and BRD4. And in MIPS, CYC2008, SGD, Aloy and TAP06 datasets, the proportion of small protein complexes is over 75%. But up to now, protein complex identification methods do not perform well in the field of small protein complexes. RESULTS: In this paper, we propose a novel method, called BOPS. It is a three-step procedure. Firstly, it calculates the balanced weights to replace the original weights. Secondly, it divides the graphs larger than MAXP until the original PPIN is divided into small PPINs. Thirdly, it enumerates the connected subset of each small PPINs, identifies potential protein complexes based on cohesion and removes those that are similar. CONCLUSIONS: In four yeast PPINs, experimental results have shown that BOPS has an improvement of about 5% compared with the SOTA model. In addition, we constructed a weighted Homo sapiens PPIN based on STRINGdb and BioGRID, and BOPS gets the best result in it. These results give new insights into the identification of small protein complexes, and the weighted Homo sapiens PPIN provides more data for related research.

A Target-Driven Self-Feedback Paper-Based Photoelectrochemical Sensing Platform for Ultrasensitive Detection of Ochratoxin A with an In2S3/WO3 Heterojunction Structure.

Currently, developing versatile, easy-to-operate, and effective signal amplification strategies hold great promise in photoelectrochemical (PEC) biosensing. Herein, an ultrasensitive polyvinylpyrrolidone-treated In2S3/WO3 (In2S3-P/WO3)-functionalized paper-based PEC sensor was established for sensing ochratoxin A (OTA) based on a target-driven self-feedback (TDSF) mechanism enabled by a dual cycling tactic of PEC chemical-chemical (PECCC) redox and exonuclease III (Exo III)-assisted complementary DNA. The In2S3-P/WO3 heterojunction structure with 3D open-structure and regulable topology was initially in situ grown on Au nanoparticle-functionalized cellulose paper, which was served as a universal signal transducer to directly record photocurrent signals without complicated electrode modification, endowing the paper chip with admirable anti-interference ability and unexceptionable photoelectric conversion efficiency. With the assistance of Exo III-assisted cycling process, a trace amount of OTA could trigger substantial signal reporter ascorbic acid (AA) generated by the enzymatic catalysis of alkaline phosphatase, which could effectively provoke the PECCC redox cycling among the tris(2-carboxyethyl)phosphine acid, AA, and ferrocenecarboxylic at the In2S3-P/WO3 photoelectrode, initiating TDSF signal amplification. Based on the TDSF process induced by the Exo III-assisted recycling and PECCC redox cycling strategy, the developed paper-based PEC biosensor realized ultrasensitive determination of OTA with persuasive selectivity, high stability, and excellent reproducibility. It is believed that the proposed paper-based PEC sensing platform exhibited enormous potential for the detection of other targets in bioanalysis and clinical diagnosis.