RBM7 deficiency promotes breast cancer metastasis by coordinating MFGE8 splicing switch and NF-kB pathway.

Aberrant alternative splicing is well-known to be closely associated with tumorigenesis of various cancers. However, the intricate mechanisms underlying breast cancer metastasis driven by deregulated splicing events remain largely unexplored. Here, we unveiled that RBM7 is decreased in lymph node and distant organ metastases of breast cancer as compared to primary lesions and low expression of RBM7 is correlated with the reduced disease-free survival of breast cancer patients. Breast cancer cells with RBM7 depletion exhibited an increased potential for lung metastasis compared to scramble control cells. The absence of RBM7 stimulated breast cancer cell migration, invasion, and angiogenesis. Mechanistically, RBM7 controlled the splicing switch of MFGE8, favoring the production of the predominant isoform of MFGE8, MFGE8-L. This resulted in the attenuation of STAT1 phosphorylation and alterations in cell adhesion molecules. MFGE8-L exerted an inhibitory effect on the migratory and invasive capability of breast cancer cells, while the truncated isoform MFGE8-S, which lack the second F5/8 type C domain had the opposite effect. In addition, RBM7 negatively regulates the NF-κB cascade and an NF-κB inhibitor could obstruct the increase in HUVEC tube formation caused by RBM7 silencing. Clinically, we noticed a positive correlation between RBM7 expression and MFGE8 exon7 inclusion in breast cancer tissues, providing new mechanistic insights for molecular-targeted therapy in combating breast cancer.

Adjustable Ultra-Light Mechanical Negative Poisson's Ratio Metamaterials with Multi-Level Dynamic Crushing Effects.

Mechanical metamaterials with multi-level dynamic crushing effects (MM-MLs) are designed in this study through coordinate transformation and mirror arrays. The mechanical effects of the diameter and length ratio of the struts and connecting rods, the Euler angles, and the cell numbers on the mechanical properties are investigated separately. MM-ML can exhibit significant two-level platform stress, and the local cells in the first platform stress stage undergo rotational motion, while the second platform stress stage mainly involves collapse compression and bending. Although increasing the length of the connecting rods can increase the range of Poisson's ratio, it will reduce the level of platform stress and energy absorption. Increasing the Euler angle will reduce the strain interval of the first platform stress and can improve the energy absorption capacity. In addition, increasing the cell number while maintaining a constant relative density can effectively enhance energy absorption. MM-ML has significant parameter controllability, can achieve different platform stress regions, different ranges of Poisson's ratios, and energy absorption requirements according to the application scenario, and can demonstrate functional diversity compared to existing research. The design scheme can provide ideas for adaptive crushing protection requirements.

Efficacy and safety of acupuncture for painful diabetic neuropathy: a systematic review and meta-analysis.

Background: Painful diabetic neuropathy (PDN) is a common chronic neurological complication of diabetes mellitus. Medications are often used to relieve pain, but with significant side effects. Acupuncture is now a component of pragmatic and integrative treatment for PDN. An increasing number of relevant randomized controlled trials have been published in recent years, but a comprehensive meta-analysis has not yet been performed. The aim of this paper is to verify the effectiveness and safety of acupuncture for PDN by meta-analysis and trial sequential analysis (TSA). Methods: All participants in this study should have had a PDN diagnosis and the trial group was treated with acupuncture. Eight databases, including EMbase, PubMed, Web of science, Cochrane Library, China Biology Medicine disc (CBM), China National Knowledge Infrastructure (CNKI), Wanfang and Chongqing VIP (CQVIP) were retrieved from inception to 5 April 2023. Meta-analysis was conducted utilizing RevMan 5.3 and Stata 15.0. TSA was performed to assess the adequacy of sample size for the outcomes. Results: A total of 36 studies, comprising 2,739 PDN patients, were included. Among them, 1,393 patients were assigned to the trial group and 1,346 patients were treated in the control group. Outcomes covers the primary indicator Total effective rate (RR = 1.42, 95%CI [1.34, 1.52], p < 0.00001), with 21 studies reported, Pain intensity (SMD = -1.27, 95%CI [-1.58, -0.95], p < 0.00001), with 23 studies reported, and other outcomes, including motor nerve conduction velocity (MCV; MD = 3.58, 95%CI [2.77, 4.38], p < 0.00001), sensory nerve conduction velocity (SCV; MD = 3.62, 95%CI [2.75, 4.49], p < 0.00001), Depression score (SMD = -1.02, 95%CI [1.58, 0.46]), Toronto clinical scoring system (TCSS; MD = -2.41, 95%CI [-3.37, -1.45], p < 0.00001), Quality of life (SMD = 1.06, 95%CI [0.66, 1.46]), traditional Chinese medicine (TCM) syndrome score (MD = -4.99, 95%CI [-6.79, -3.18], p < 0.00001), suggesting that acupuncture have an ameliorating effect on PDN in various respect. Egger's test revealed publication bias for four outcomes. TSA showed that as for Total effective rate, Pain Intensity, MCV and SCV, the number of included studies was sufficient to support the conclusions. Conclusion: Acupuncture demonstrates significant effectiveness in improving PDN outcomes, including Total effective rate, Pain intensity, MCV, SCV, Depression score, TCSS, Quality of life, TCM syndrome score. But the Adverse events rate is no different in trail group and control group. The publication bias presented in Total effective rate, Pain intensity, MCV and SCV can be remedied by Trim and filling method. Systematic review registration: Prospero, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=477295.

Hierarchical NiCo2Se4 Arrays Composed of Atomically Thin Nanosheets: Simultaneous Improvements in Thermodynamics and Kinetics for Electrocatalytic Water Splitting in Neutral Media.

The inefficiency of electrocatalysts for water splitting in neutral media stems from a comprehensive impact of poor intrinsic activity, a limited number of active sites, and inadequate mass transport. Herein, hierarchical ultrathin NiCo2Se4 nanosheets are synthesized by the selenization of NiCo2O4 porous nanoneedles. Theoretical and experimental investigations reveal that the intrinsic hydrogen evolution reaction (HER) activity primarily originate from the NiCo2Se4, whereas the high oxygen evolution reaction (OER) performance is related to the NiCoOOH due to the structural reconstruction. The abundant Se and O vacancies introduced by atomically thin nanostructure modulate the electronic structure of NiCo2Se4 and NiCoOOH, thereby improving the intrinsic HER and OER activities, respectively. COMSOL simulation demonstrate the edges of extended nanosheets from the main body significantly promote the charge aggregation, boosting the reduction and oxidation current during HER/OER process. This charge aggregation effect notably exceeds the tip effect for the nanoneedle, highlighting the unique advantage of the hierarchical nanosheet structure. Benefiting from abundant vacancies and unique nanostructure, the hierarchical ultrathin nanosheet simultaneously improve the thermodynamics and kinetics of the electrocatalyst. The optimized samples display an overpotential of 92 mV for HER and 214 mV for OER at 100 mA cm-2, significantly surpassing the performance of currently reported HER/OER catalysts in neutral media.

Cognition of diet quality and dietary management in elderly patients with coronary and other atherosclerotic vascular disease in western China, a qualitative research study.

BACKGROUND: Healthy eating is one of the most important nonpharmacologic treatments for patients with atherosclerosis(AS). However, it is unclear how elderly AS patients in western China perceive their dietary status and which type of nutritional assistance they would be willing to receive. Therefore, the primary purpose of this study was to understand the level of knowledge about current dietary habits and healthy eating habits among elderly AS patients in western China, and the secondary purpose was to identify acceptable nutritional assistance measures or pathways for those patients to help them manage disease progression. METHODS: An implementation study approach was used to recruit elderly patients with AS-related diseases in western China for semistructured interviews. RESULTS: 14 participants were included in the study, and the following three themes were identified from the interviews:(1) the diet with regional characteristics; (2) low nutrition-related health literacy; (3) complex attitudes towards nutritional assistance. Most participants had misconceptions about healthy eating, and the sources of their knowledge might not be trustworthy. Participants expressed a preference for personalized nutritional assistance, especially that provided by medical-nursing combined institutions. CONCLUSION: Patients in western China need nutritional assistance for their regional dietary habits; therefore, healthy dietary patterns consistent with the regional culture are proposed to improve the prevailing lack of knowledge about healthy diets, improve the dietary structure of patients, and control the development of the disease.

Rich-club organization of whole-brain spatio-temporal multilayer functional connectivity networks.

Objective: In this work, we propose a novel method for constructing whole-brain spatio-temporal multilayer functional connectivity networks (FCNs) and four innovative rich-club metrics. Methods: Spatio-temporal multilayer FCNs achieve a high-order representation of the spatio-temporal dynamic characteristics of brain networks by combining the sliding time window method with graph theory and hypergraph theory. The four proposed rich-club scales are based on the dynamic changes in rich-club node identity, providing a parameterized description of the topological dynamic characteristics of brain networks from both temporal and spatial perspectives. The proposed method was validated in three independent differential analysis experiments: male-female gender difference analysis, analysis of abnormality in patients with autism spectrum disorders (ASD), and individual difference analysis. Results: The proposed method yielded results consistent with previous relevant studies and revealed some innovative findings. For instance, the dynamic topological characteristics of specific white matter regions effectively reflected individual differences. The increased abnormality in internal functional connectivity within the basal ganglia may be a contributing factor to the occurrence of repetitive or restrictive behaviors in ASD patients. Conclusion: The proposed methodology provides an efficacious approach for constructing whole-brain spatio-temporal multilayer FCNs and conducting analysis of their dynamic topological structures. The dynamic topological characteristics of spatio-temporal multilayer FCNs may offer new insights into physiological variations and pathological abnormalities in neuroscience.

Mixed effects of ambient air pollutants on oocyte-related outcomes: A novel insight from women undergoing assisted reproductive technology.

Air pollution is widely acknowledged as a significant risk factor for human health, especially reproductive health. Nevertheless, many studies have disregarded the potentially mixed effects of air pollutants on reproductive outcomes. We performed a retrospective cohort study involving 8048 women with 9445 cycles undergoing In Vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI) in China, from 2017 to 2021. A land-use random forest model was applied to estimate daily residential exposure to air pollutants, including sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), and fine particulate matter (PM2.5). Individual and joint associations between air pollutants and oocyte-related outcomes of ART were evaluated. In 90 days prior to oocyte pick-up to oocyte pick-up (period A), NO2, O3 and CO was negatively associated with total oocyte yield. In the 90 days prior to oocyte pick-up to start of gonadotropin medication (Gn start, period B), there was a negative dose-dependent association of exposure to five air pollutants with total oocyte yield and mature oocyte yield. In Qgcomp analysis, increasing the multiple air pollutants mixtures by one quartile was related to reducing the number of oocyte pick-ups by -2.00 % (95 %CI: -2.78 %, -1.22 %) in period A, -2.62 % (95 %CI: -3.40 %, -1.84 %) in period B, and -0.98 % (95 %CI: -1.75 %, -0.21 %) in period C. During period B, a 1-unit increase in the WQS index of multiple air pollutants exposure was associated with fewer number of total oocyte (-1.27 %, 95 %CI: -2.16 %, -0.36 %) and mature oocyte (-1.42 %, 95 %CI: -2.41 %, -0.43 %). O3 and NO2 were major contributors with adverse effects on the mixed associations. Additionally, period B appears to be the susceptible window. Our study implies that exposure to air pollution adversely affects oocyte-related outcomes, which raises concerns about the potential adverse impact of air pollution on women's reproductive health.

Enhanced recovery after surgery in percutaneous transhepatic cholangioscopic lithotripsy for patients with hepatolithiasis and choledocholithiasis.

Background: Percutaneous transhepatic cholangioscopic lithotripsy (PTCSL) provides an effective alternative procedure for the management of complex hepatolithiasis and choledocholithiasis. Enhanced recovery after surgery (ERAS) program is an evidence-based approach that was developed to reduce surgical stress and accelerate postoperative recovery. However, little is known regarding PTCSL in the context of ERAS. The aim of this study was to evaluate the efficacy and safety of PTCSL within ERAS programs. Patient and methods: The clinical data of patients who underwent PTCSL within ERAS programs consulted at our hospital between November 2017 and November 2022 was retrospectively reviewed. Individualized perioperative ERAS items were evaluated for all patients. The demographics, intraoperative variables, and postoperative outcomes were analyzed. Results: A total of 43 patients who underwent PTCSL were included in the study. There were 13 men and 30 women aged between 39 and 89 years with an average age of 60 years (60.49 ± 12.37). The stone clearance rate was 77 % after the first operation, and the final clearance rate was 95 %. The incidence of complications in this study is 18.6 % (8/43), including 6 patients with Clavien-Dindo I-II, and 2 patients with Clavien-Dindo III. Pleural effusion, abdominal effusion, infection, bile leakage, and biliary bleeding are the most common complications, however, all patients recovered after aggressive treatment. Conclusion: PTCSL is a relatively safe, feasible, and efficient method for treating complex hepatolithiasis and choledocholithiasis within ERAS programs. Individualized ERAS entries and precise disease management are required to minimize the occurrence of complications and to provide effective treatment.

Redispersing Ir Nanoparticles via a Carbon-Assisted Pyrolysis Process to Break the Activity-Stability Trade-Off of H2 Sensors.

Oxide semiconductor-supported metal nanoparticles often suffer from a high-temperature gas sensing process, resulting in agglomeration and coalescence, which significantly decrease their surface activity and stability. Here, we develop an in situ pyrolysis strategy to redisperse commercial Ir particles (∼15.6 nm) into monodisperse Ir species (∼5.4 nm) on ZnO supports, exhibiting excellent sintering-resistant properties and H2 sensing. We find that large-size Ir nanoparticles can undergo an unexpected splitting decomposition process and spontaneously migrate along the encapsulated carbon layer surface during high-temperature pyrolysis of ZIF-8. This resultant monodisperse status can be integrally reserved, accompanying further oxidation sintering. The final Irred/ZnO-450-based sensor exhibits outstanding stability, H2 response (10-2000 ppm), fast response/recovery capability (7/9.7 s@100 ppm), and good moisture resistance. In situ Raman and ex situ XPS further experimentally verify that highly dispersive Ir species can promote the electron transfer process during the gas sensing process. Our strategy thus provides important insights into the design of agglomeration-resistant gas sensing materials for highly effective H2 detection.

Dynamics of radionuclide electromigration in intact granite: An kinetic adsorption-advection-dispersion model and its application.

Granite, as the natural barrier for the disposal of high-level radioactive waste, plays an important role in ensuring environmental and public safety. The safety assessment of the repository depends on the reliable migration parameters of radionuclides in granite. In this study, we developed a kinetic adsorption-advection-dispersion model based on first-order adsorption kinetics. It introduces a first-order adsorption rate coefficient to describe the kinetics of adsorption process and accounts for other crucial mechanisms affecting the migration of radionuclide ions, namely, the electromigration, electroosmosis, and dispersion. This model is then applied to interpret the experimental results of electromigration of tracer ions in intact granite. The results show that for the weakly adsorbed radionuclides studied, iodide and selenite, the effective diffusion coefficients and formation factors calculated by this model are in constant with those derived from the classical advection-dispersion model based on linear adsorption equilibrium. By contrast, for the moderately or strongly adsorbed tracer ions studied, including cobalt, cesium, and strontium, the migration parameters calculated by this model exhibit significantly less uncertainty than those obtained from the advection-dispersion model simulations. The advection-dispersion model based on the first order adsorption kinetics introduces the first order adsorption rate coefficient, and considers the influence of electromigration, electroosmosis and dispersion mechanism, which helps to explain the migration mechanism of nuclide ions in intact granite more accurately.

Integrated phenotypic, transcriptomics and metabolomics: growth status and metabolite accumulation pattern of medicinal materials at different harvest periods of Astragalus Membranaceus Mongholicus.

BACKGROUND: Astragalus membranaceus var. mongholicus (Astragalus), acknowledged as a pivotal "One Root of Medicine and Food", boasts dual applications in both culinary and medicinal domains. The growth and metabolite accumulation of medicinal roots during the harvest period is intricately regulated by a transcriptional regulatory network. One key challenge is to accurately pinpoint the harvest date during the transition from conventional yield content of medicinal materials to high and to identify the core regulators governing such a critical transition. To solve this problem, we performed a correlation analysis of phenotypic, transcriptome, and metabolome dynamics during the harvesting of Astragalus roots. RESULTS: First, our analysis identified stage-specific expression patterns for a significant proportion of the Astragalus root genes and unraveled the chronology of events that happen at the early and later stages of root harvest. Then, the results showed that different root developmental stages can be depicted by co-expressed genes of Astragalus. Moreover, we identified the key components and transcriptional regulation processes that determine root development during harvest. Furthermore, through correlating phenotypes, transcriptomes, and metabolomes at different harvesting periods, period D (Nov.6) was identified as the critical period of yield and flavonoid content increase, which is consistent with morphological and metabolic changes. In particular, we identified a flavonoid biosynthesis metabolite, isoliquiritigenin, as a core regulator of the synthesis of associated secondary metabolites in Astragalus. Further analyses and experiments showed that HMGCR, 4CL, CHS, and SQLE, along with its associated differentially expressed genes, induced conversion of metabolism processes, including the biosynthesis of isoflavones and triterpenoid saponins substances, thus leading to the transition to higher medicinal materials yield and active ingredient content. CONCLUSIONS: The findings of this work will clarify the differences in the biosynthetic mechanism of astragaloside IV and calycosin 7-O-ß-D-glucopyranoside accumulation between the four harvesting periods, which will guide the harvesting and production of Astragalus.

Imidazole functionalized photo-crosslinked aliphatic polycarbonate drug-eluting coatings on zinc alloys for osteogenesis, angiogenesis, and bacteriostasis in bone regeneration.

Zinc (Zn) alloys have demonstrated significant potential in healing critical-sized bone defects. However, the clinical application of Zn alloys implants is still hindered by challenges including excessive release of zinc ions (Zn2+), particularly in the early stage of implantation, and absence of bio-functions related to complex bone repair processes. Herein, a biodegradable aliphatic polycarbonate drug-eluting coating was fabricated on zinc-lithium (Zn-Li) alloys to inhibit Zn2+ release and enhance the osteogenesis, angiogenesis, and bacteriostasis of Zn alloys. Specifically, the photo-curable aliphatic polycarbonates were co-assembled with simvastatin and deposited onto Zn alloys to produce a drug-loaded coating, which was crosslinked by subsequent UV light irradiation. During the 60 days long-term immersion test, the coating showed distinguished stable drug release and Zn2+ release inhibition properties. Benefiting from the regulated release of Zn2+ and simvastatin, the coating facilitated the adhesion, proliferation, and differentiation of MC3T3-E1 cells, as well as the migration and tube formation of EA.hy926 cells. Astonishingly, the coating also showed remarkable antibacterial properties against both S. aureus and E. coli. The in vivo rabbit critical-size femur bone defects model demonstrated that the drug-eluting coating could efficiently promote new bone formation and the expression of platelet endothelial cell adhesion molecule-1 (CD31) and osteocalcin (OCN). The enhancement of osteogenesis, angiogenesis, and bacteriostasis is achieved by precisely controlling of the released Zn2+ at an appropriate level, as well as the stable release profile of simvastatin. This tailored aliphatic polycarbonate drug-eluting coating provides significant potential for clinical applications of Zn alloys implants.

[Clinical effect of acupuncture combined with medication on diabetic peripheral neuropathy and its influence on serum lipid metabolism].

OBJECTIVE: To observe the clinical effect on diabetic peripheral neuropathy (DPN) treated with acupuncture combined with medication and explore its effect mechanism. METHODS: Sixty-two patients of DPN were randomly divided into a combined therapy group (31 cases) and a medication group (31 cases, 2 cases dropped out); besides, 20 healthy subjects were recruited as a normal group. On the base of routine intervention, in the medication group, thioctic acid capsules were administrated orally, 0.2 g each time, 3 times a day. In the combined therapy group, besides the medication as the medication group, acupuncture was performed on bilateral Quchi (LI 11), Waiguan (TE 5), Hegu (LI 4), Tianshu (ST 25), Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3) and the needles were retained for 30 min, acupuncture was delivered once daily, 6 times a week. The duration of treatment was 4 weeks in the two groups. The score of Toronto clinical scoring system (TCSS), the nerve conduction velocity of median nerve (MN) and common peroneal nerve (CPN) were observed before and after treatment in the two intervention groups; and the serum lipid metabolism was detected before and after treatment in the two intervention groups and the normal group. RESULTS: Compared with that before treatment, the scores of TCSS were reduced in the combined therapy group and the medication group (P<0.05) after treatment, and the score decrease in the combined therapy group was larger than that of the medication group (P<0.001). The motor nerve conduction velocity and the sensory nerve conductive velocity of MN and CPN after treatment all increased in the combined therapy group and the medication group compared with those before treatment (P<0.05), and the improvements in the combined therapy group were larger than those of the medication group (P<0.001). Before treatment DPN patients had 365 differential lipid metabolites, including sphingosine (SPH, d18:0), involved in the inositol phosphate metabolism, compared with the subjects of the normal group. There were 103 differential lipid metabolites in the medication group before and after treatment, including lysophosphatidyl ethanolamine (LPE, 18:1/0:0), participated in glycerophospholipid metabolism. In the combined therapy group, before and after treatment, there were 99 differential lipid metabolites, including lysophosphatidylcholine (LPC, 18:0/0:0), participated in the neuroactive ligand-receptor interaction. Acupuncture greatly affected 50 lipid metabolites such as lysophosphatidic acid (LPA, 0:0/22:6), LPA(0:0/18:2) and LPC(O-18:0), which was mainly involved in glycerophospholipid metabolism. CONCLUSION: Acupuncture combined with medication ameliorates the symptoms and the nerve conduction velocity in DPN patients, which may be related to the regulation of serum lipid metabolism.

NUCB2 inhibition antagonizes osteosarcoma progression and promotes anti-tumor immunity through inactivating NUCKS1/CXCL8 axis.

The oncogenic properties of Nucleobindin2 (NUCB2) have been observed in various cancer types. Nevertheless, the precise understanding of the biological functions and regulatory mechanisms of NUCB2 in osteosarcoma remains limited. This investigation reported that NUCB2 was significantly increased upon glucose deprivation-induced metabolic stress. Elevated NUCB2 suppressed glucose deprivation-induced cell death and reactive oxygen species (ROS) increase. Depletion of NUCB2 resulted in a reduction in osteosarcoma cell proliferation as well as metastatic potential in vitro and in vivo. Mechanically, NUCB2 ablation suppressed C-X-C Motif Chemokine Ligand 8 (CXCL8) expression which then reduced programmed cell death 1 ligand 1 (PD-L1) expression and stimulated anti-tumor immunity mediated through cytotoxic T cells. Importantly, a combination of NUCB2 depletion with anti-PD-L1 treatment improved anti-tumor T-cell immunity in vivo. Moreover, we further demonstrated that NUCB2 interacted with NUCKS1 to inhibit its degradation, which is responsible for the transcriptional regulation of CXCL8 expression. Altogether, the outcome emphasizes the function of NUCB2 in osteosarcoma and indicates that NUCB2 elevates osteosarcoma progression and immunosuppressive microenvironment through the NUCKS1/CXCL8 pathway.

Xuebijing injection and its bioactive components alleviate nephrotic syndrome by inhibiting podocyte inflammatory injury.

Xuebijing injection (XBJ) is widely used to treat nephrotic syndrome (NS) in clinic, but its bioactive components and therapeutic mechanism are still unclear. In this study, the bioactive components of XBJ were determined by ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS). The therapeutic effect of XBJ on NS was evaluated in BALB/c mice induced by adriamycin (ADR, 10 mg/kg) via a single tail vein. The protective effect of XBJ and its bioactive components on podocytes was demonstrated using mouse podocytes (MPC-5) induced by lipopolysaccharide (LPS, 4 µg/mL). The results show that 33 components of XBJ were identified. Furthermore, 12 bioactive components were detected in blood, including protocatechuic acid, salvianolic acid C, benzoyloxypaeoniflorin, danshensu, salvianolic acid A, salvianolic acid B, catechin, caffeic acid, galloylpaeoniflorin, oxypaeoniflorin, hydroxysafflor yellow A, rosmarinic acid. The relative content (%) of the bioactive components were 59.32, 16.01, 9.97, 9.73, 8.72, 8.31, 7.92, 6.54, 1.54, 1.30, 0.68 and 0.59 in this order. After XBJ treatment, the renal function, hyperlipidemia and renal pathological damage were improved in NS model mice. Moreover, the levels of nephrin and desmin which are functional proteins in podocytes were reversed, and the levels of pro-inflammatory factors were reduced by XBJ. Interestingly, protocatechuic acid and salvianolic acid C also showed good protective effects on podocyte function and reduced the level of inflammation in LPS-induced MPC-5. The study is the first time to elucidate the bioactive components of XBJ and its potential therapeutic mechanism for treating NS by protecting podocyte function.

KLF4 suppresses anticancer effects of brusatol via transcriptional upregulating NCK2 expression in melanoma.

Brusatol (Bru), a main extract from traditional Chinese medicine Brucea javanica, has been reported to exist antitumor effect in many tumors including melanoma. However, the underlying mechanism in its anti-melanoma effect still need further exploration. Here, we reported that the protein expression of KLF4 in melanoma cells were significantly downregulated in response to brusatol treatment. Overexpression of KLF4 suppressed brusatol-induced melanoma cell apoptosis; while knockdown of KLF4 enhanced antitumor effects of brusatol on melanoma cells not only in vitro but also in vivo. Further studies on the mechanism revealed that KLF4 bound to the promoter of NCK2 directly and facilitated NCK2 transcription, which suppressed the antitumor effect of brusatol on melanoma. Furthermore, our findings showed that miR-150-3p was dramatically upregulated under brusatol treatment which resulted in the downregulation of KLF4. Our results suggested that the miR-150-3p/KLF4/NCK2 axis might play an important role in the antitumour effects of brusatol in melanoma.

HOXB9 promotes osteosarcoma cell survival and malignancy under glucose starvation via upregulating SPP1 expression.

Homeobox B9 (HOXB9) has been shown to play a critical role in several tumors. However, the precise biological mechanisms and functions of HOXB9 in osteosarcoma remain largely unknown. In this study, we found that HOXB9 was increased upon glucose starvation. Elevated HOXB9 suppressed osteosarcoma cell death and supported cell growth and migration under glucose starvation. Further mechanistic studies demonstrated that HOXB9 directly bound to the promoter of secreted phosphoprotein 1 (SPP1) and transcriptionally upregulated SPP1 expression which then led cell death decrease and cell growth increase under glucose deprivation environment. Clinically, HOXB9 was significantly upregulated in osteosarcoma compared with normal tissues and increase of HOXB9 expression was positively associated with the elevation of SPP1 in osteosarcoma. Overall, our study illustrates that HOXB9 contributes to malignancy in osteosarcoma and inhibits cell death through transcriptional upregulating SPP1 under glucose starvation.

Effects of Glutathione S-Transferases (GSTM1, GSTT1 and GSTP1) gene variants in combination with smoking or drinking on cancers: A meta-analysis.

BACKGROUND: This meta-analysis aimed to systematically summarize the association between cancer risks and glutathione s-transferases (GSTs) among smokers and drinkers. METHODS: Literature was searched through PubMed, Web of Science, CNKI, and WANFANG published from 2001 to 2022. Stata was used with fixed-effect model or random-effect model to calculate pooled odds ratios (ORs) and the 95% confidence interval (95% CI). Sensitivity and heterogeneity calculations were performed, and publication bias was analyzed by Begg and Egger's test. Regression analysis was performed on the correlated variables about heterogeneity, and the false-positive report probabilities (FPRP) and the Bayesian False Discovery Probability (BFDP) were calculated to assess the confidence of a statistically significant association. RESULTS: A total of 85 studies were eligible for GSTs and cancer with smoking status (19,604 cases and 23,710 controls), including 14 articles referring to drinking status (4409 cases and 5645 controls). GSTM1-null had significant associations with cancer risks (for smokers: OR = 1.347, 95% CI: 1.196-1.516, P < .001; for nonsmokers: OR = 1.423, 95% CI: 1.270-1.594, P < .001; for drinkers: OR = 1.748, 95% CI: 1.093-2.797, P = .02). GSTT1-null had significant associations with cancer risks (for smokers: OR = 1.356, 95% CI: 1.114-1.651, P = .002; for nonsmokers: OR = 1.103, 95% CI: 1.011-1.204, P = .028; for drinkers: OR = 1.423, 95% CI: 1.042-1.942, P = .026; for nondrinkers: OR = 1.458, 95% CI: 1.014-2.098, P = .042). Negative associations were found between GSTP1rs1695(AG + GG/AA) and cancer risks among nondrinkers (OR = 0.840, 95% CI: 0.711-0.985, P = .032). CONCLUSIONS: GSTM1-null and GSTT1-null might be related cancers in combination with smoking or drinking, and GSTP1rs1695 might be associated with cancers among drinkers.

Space-Efficient 3D Microalgae Farming with Optimized Resource Utilization for Regenerative Food.

Photosynthetic microalgae produce valuable metabolites and are a source of sustainable food that supports life without compromising arable land. However, the light self-shading, excessive water supply, and insufficient space utilization in microalgae farming have limited its potential in the inland areas most in need of regenerative food solutions. Herein, this work develops a 3D polysaccharide-based hydrogel scaffold for vertically farming microalgae without needing liquid media. This liquid-free strategy is compatible with diverse microalgal species and enables the design of living microalgal frameworks with customizable architectures that enhance light and water utilization. This approach significantly increases microalgae yield per unit water consumption, with an 8.8-fold increase compared to traditional methods. Furthermore, the dehydrated hydrogels demonstrate a reduced size and weight (≈70% reduction), but readily recover their vitality upon rehydration. Importantly, valuable natural products can be produced in this system including proteins, carbohydrates, lipids, and carotenoids. This study streamlines microalgae regenerative farming for low-carbon biomanufacturing by minimizing light self-shading, relieving water supply, and reducing physical footprints, and democratizing access to efficient aquatic food production.