Abnormal dynamic functional connectivity in young nondisabling intracerebral hemorrhage patients.

OBJECTIVE: Previous resting-state functional magnetic resonance imaging studies on intracerebral hemorrhage patients have focused more on the static characteristics of brain activity, while the time-varying effects during scanning have received less attention. Therefore, the current study aimed to explore the dynamic functional network connectivity changes of intracerebral hemorrhage patients. METHODS: Using independent component analysis, the sliding window approach, and the k-means clustering analysis method, different dynamic functional network connectivity states were detected from resting-state functional magnetic resonance imaging data of 37 intracerebral hemorrhage patients and 44 healthy controls. The inter-group differences in dynamic functional network connectivity patterns and temporal properties were investigated, followed by correlation analyses between clinical scales and abnormal functional indexes. RESULTS: Ten resting-state networks were identified, and the dynamic functional network connectivity matrices were clustered into four different states. The transition numbers were decreased in the intracerebral hemorrhage patients compared with healthy controls, which was associated with trail making test scores in patients. The cerebellar network and executive control network connectivity in State 1 was reduced in patients, and this abnormal dynamic functional connectivity was positively correlated with the animal fluency test scores of patients. INTERPRETATION: The current study demonstrated the characteristics of dynamic functional network connectivity in intracerebral hemorrhage patients and revealed that abnormal temporal properties and functional connectivity may be related to the performance of different cognitive domains after ictus. These results may provide new insights into exploring the neurocognitive mechanisms of intracerebral hemorrhage.

Synthesis and characterizations of MoS2 nanoflowers and spectroscopic study of their interaction with bovine serum albumin.

Molybdenum disulfide nanoflowers (MoS2 NFs) were prepared by hydrothermal method. The prepared MoS2 NFs was characterized by SEM, TEM, XRD, specific surface areas, Raman and XPS. The characterization results show that the flower-like spherical MoS2 is composed of many ultra-thin nanosheets with an average diameter of about 300-400 nm. MoS2 NFs also exhibits excellent absorption and high fluorescence intensity. In order to explore the biological behavior of MoS2 NFs, the interaction between MoS2 NFs and bovine serum albumin (BSA) was studied by UV-Vis absorption, fluorescence, synchronous fluorescence spectra, and cyclic voltammetry. The results of absorption and fluorescence show that MoS2 NFs and BSA interact strongly through the formation of complexes. The Stern-Volmer constant and the quenching constant was calculated about 3.79×107 L mol-1 and 3.79×1015 L mol-1 s-1, respectively. The synchronous fluorescence implied that MoS2 in the complex may mainly bind to tryptophan residues of BSA. The cyclic voltammograms indicated that the addition of BSA makes electron reduction of MoS2 NFs more difficult than the corresponding free state. These experimental results clarified the effective transportation and elimination of MoS2 NFs in the body by binding to BSA, and can provide useful guideline for estimating MoS2 NFs as a drug carrier.

Application and potential value of curcumin in prostate cancer: a meta-analysis based on animal models.

Introduction: Curcumin is gaining recognition as an agent for cancer chemoprevention and is presently administered to humans. However, the limited number of clinical trials conducted for the treatment of prostate cancer is noteworthy. Animal models serve as valuable tools for enhancing our understanding of disease mechanisms and etiology in humans. The objective of this study was to examine the anti-prostate cancer effects of curcumin in vivo for comprehending its current research status and potential clinical applicability. Methods: Our methodology involved a systematic exploration of animal studies pertaining to curcumin and prostate cancer, as documented in PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang database, Vip database, and SinoMed, up to 03 September 2023. Risk of bias was assessed using the SYRCLE Animal Study Risk of Bias tool. The results were combined using the RevMan 5.3. Results: A comprehensive analysis was conducted on 17 studies encompassing 263 mouse transplantation tumor models. The findings of this meta-analysis demonstrated that curcumin exhibited a superior inhibitory effect on the volume of prostate cancer tumors in mice compared to the control group (standardized mean difference [SMD]: 1.16, 95% confidence interval [CI]: 0.52, 1.80, p < 0.001). Additionally, curcumin displayed a more effective inhibition of mice prostate cancer tumor weight (SMD: -3.27, 95% CI: -4.70, -1.83, p < 0.001). Furthermore, in terms of tumor inhibition rate, curcumin exhibited greater efficacy (SMD: 0.25, 95% CI: 0.23, 0.27, p < 0.001). Moreover, curcumin more effectively inhibited PCNA mRNA (SMD: -3.11, 95% CI: -4.60, -1.63, p < 0.001) and MMP2 mRNA (SMD: -3.19, 95% CI: 5.85, -0.53, p < 0.001). Conclusion: Curcumin exhibited inhibitory properties towards prostate tumor growth and demonstrated a beneficial effect on prostate cancer treatment, thereby offering substantiation for further clinical investigations. It is important to acknowledge that the included animal studies exhibited considerable heterogeneity, primarily because of the limited number of studies included. Consequently, additional randomized controlled trials are required to comprehensively assess the efficacy of curcumin in humans. Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023464661), identifier (CRD42023464661).

The Role of JAK/STAT Signaling Pathway and Its Downstream Influencing Factors in the Treatment of Atherosclerosis.

Atherosclerosis is now widely considered to be a chronic inflammatory disease, with increasing evidence suggesting that lipid alone is not the main factor contributing to its development. Rather, atherosclerotic plaques contain a significant amount of inflammatory cells, characterized by the accumulation of monocytes and lymphocytes on the vessel wall. This suggests that inflammation may play a crucial role in the occurrence and progression of atherosclerosis. As research deepens, other pathological factors have also been found to influence the development of the disease. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is a recently discovered target of inflammation that has gained attention in recent years. Numerous studies have provided evidence for the causal role of this pathway in atherosclerosis, and its downstream signaling factors play a significant role in this process. This brief review aims to explore the crucial role of the JAK/STAT pathway and its representative downstream signaling factors in the development of atherosclerosis. It provides a new theoretical basis for clinically affecting the development of atherosclerosis by interfering with the JAK/STAT signaling pathway.

Detection of intracellular microRNA-21 for cancer diagnosis by a nanosystem containing a ZnO@polydopamine and DNAzyme probe.

MicroRNAs (miRNAs) are a series of single-stranded non-coding ribonucleic acid (RNA) molecules which associated closely with various human diseases. Efficient strategies for detecting miRNAs are of great significance to cancer diagnosis and prognosis. Here we provide a novel nanosystem that can be applied for the detection of miRNAs. The nanosystem consists of a single-stranded deoxyribonucleic acid (DNA) probe and a probe carrier. The DNA probe was designed based on a deoxyribozyme (DNAzyme) with several necessary functional sequences and two fluorescent dyes labeled at proper sites. The ZnO@polydopamine (ZnO@PDA) nanomaterial serves not only as a probe carrier, but also as a supplier of Zn2+ that can activate the DNAzyme. The DNA probe will undergo a conformation alteration induced by miRNA-21, which then trigger the DNAzyme catalyzed self-cleavage reaction with the assist of Zn2+ provided by ZnO decomposition under weak acid environment. A change of fluorescent color will occur due to the interruption of fluorescence resonance energy transfer between the two fluorescent dyes, and the dissociated miRNA-21 can repeatedly induce the above responses to amplify the fluorescence signal. The feasibility of the whole procedure was demonstrated by various experiments. This nanosystem showed a good selectivity towards miRNA-21, and under the optimal incubation time of 2 hours, a good linear relationship was obtained in a concentration range of 0.01-2.0 nM with a detection limit of 3.8 pM. In in vivo detection, an obvious fluorescence color change from red to green can be observed in the presence of miRNA-21. The results proved that this miRNA detection strategy has a broad application prospect in tumor diagnosis and miRNA related biological studies.

Natural variation in SSW1 coordinates seed growth and nitrogen use efficiency in Arabidopsis.

Seed size is controlled not only by intrinsic genetic factors but also by external environmental signals. Here, we report a major quantitative trait locus (QTL) gene for seed size and weight on chromosome 1 (SSW1) in Arabidopsis, and we found SSW1 acts maternally to positively regulate seed size. Natural variation in SSW1 contains three types of alleles. The SSW1Cvi allele produces larger seeds with more amino acid and storage protein contents than the SSW1Ler allele. SSW1Cvi displays higher capacity for amino acid transport than SSW1Ler due to the differences in transport efficiency. Under low nitrogen supply, the SSW1Cvi allele exhibits increased seed yield and nitrogen use efficiency (NUE). Locations of natural variation alleles of SSW1 are associated with local soil nitrogen contents, suggesting that SSW1 might contribute to geographical adaptation in Arabidopsis. Thus, our findings reveal a mechanism that coordinates seed growth and NUE, suggesting a potential target for improving seed yield and NUE in crops.

GmMATE100 Is Involved in the Import of Soyasaponins A and B into Vacuoles in Soybean Plants (Glycine max L.).

Triterpenoid saponins, synthesized via the mevalonic acid (MVA) pathway in the cytoplasm, provide protection against pathogens and pests in plants and health benefits for humans. However, the mechanisms by which triterpenoid saponins are transported between cellular compartments remain uncharacterized. Here, we characterize a tonoplast localized multidrug and toxic compound extrusion transporter, GmMATE100 (encoded by Glyma.18G143700), from soybean (Glycine max L.). GmMATE100 is co-expressed with soyasaponin biosynthetic genes, and its expression was induced by MeJA treatment, which also led to soyasaponin accumulation in soybean roots. GmMATE100 efficiently transports multiple type-B soyasaponins as well as type-A soyasaponins with low affinity from the cytosol to the vacuole in a yeast system. The GmMATE100 loss-of-function mutant showed a significant decrease in type-A and type-B soyasaponin contents in soybean roots. This study not only characterized the first soybean triterpenoid saponin transporter but also provided new knowledge for the rational engineering of soyasaponin content and composition in soybean plants to modulate their levels within crop environments.

Efficacy and safety of Chinese patent medicine in the adjuvant treatment of prostate cancer: A Bayesian network meta-analysis.

BACKGROUND: Prostate cancer is the most common cancer in men. In China, traditional Chinese medicine is used to treat prostate cancer. However, there is a lack of evidence for differences in the effectiveness and safety of different Chinese patent medicines. Therefore, we conducted this Network Meta-analysis to investigate the efficacy and safety of different Chinese patent medicines in the treatment of prostate cancer. METHODS: We systematically search PubMed, Web of Science, Embase, Cochrane library, CNKI database, VIP database, wanfang database, and SinoMed Randomized controlled trials of Chinese patent medicines for the treatment of prostate cancer sores included in the database were retrieved until June 1, 2023. The included studies were assessed for risk of bias using Cochrane randomized controlled trial Bias risk Assessment tool. The main outcome indicators were Efficacy, Prostate Specific Antigen, and adverse reaction. Since different courses of treatment were used in the included studies, we used Bayesian mesh meta-regression to investigate the effects of treatment courses on efficacy and safety. RESULTS: Twenty-seven articles were included, involving 1885 patients. Including 9 kinds of Chinese patent medicine. The results of Network Meta-analysis show that: ① efficacy: compared with androgen antagonists, Bruceolic oil emulsion (relative risk = 1.70, 95% credibility interval [CI] (1.30, 2.29)), Compound Kushen injection (relative risk = 1.39, 95%CI (1.19, 1.70)) had significant advantages. There was no significant difference among all Chinese patent medicines (P > .05). The top 3 Chinese patent medicines were Bruceolic oil emulsion, Zhibodihuang pill, Compound Kushen injection. ② Prostate specific antigen: compared with androgen antagonists, Bruceolic oil emulsion (mean difference [MD] = -10.4, 95%CI [-17.6, -3.21]), Compound Kushen injection (MD = -4.46, 95%CI [-8.80, -1.70]), Shenfu injection (MD = -14.7, 95%CI [-23.4, -6.01]) had significant advantages. The top 3 Chinese patent medicines were Shenfu injection, Bruceolic oil emulsion, Compound Kushen injection. adverse reaction: compared with androgen antagonists, there was no significant difference among all PCM (P > .05). CONCLUSION: Compared with androgen antagonists, Chinese patent medicine has significant difference in effectiveness. The effect of Chinese patent medicine is little affected by the course of treatment and dose. From comprehensive analysis, Bruceolic oil emulsion combined with androgen antagonist is the best intervention measures.

The aggregation behavior between soybean whey protein and polysaccharides of diverse structures and their implications in soybean isoflavone delivery.

The use of polysaccharides to recover soybean whey protein (SWP) from whey wastewater is recognized as an effective approach. However, the recovery rate can vary due to differences in the structure and compound ratios of the polysaccharides involved. The interaction between SWP and polysaccharides (sodium alginate, SA; chitosan, CHI; carrageenan, CAR) at different ratio was investigated. We harnessed these complexes to fabricate emulsions aimed at delivering soybean isoflavones. The results showed that the addition of polysaccharides unfolded the structure of SWP. The intermolecular hydrogen bonds within SWP-SA were stronger than those of the other complexes. These structural changes showed consistency across different ratios. The mean particle size of the complexes increased. SWP-SA exhibited the lowest interfacial tension. The emulsion with SWP-SA at 300 W demonstrated superior stability, and the bioavailability of soybean isoflavones increased by 3-6 %. These results shed light on the promising potential of polysaccharide-based strategies for SWP recovery and the effective delivery of soybean isoflavones.

Alleviation of behavioral deficits, amyloid-ß deposition, and mitochondrial structure damage associated with mitophagy upregulation in AD animal models via AAV9-IGF-1 treatment.

By safeguarding the neurological system, insulin-like growth factor 1 (IGF-1) may have a role in the etiology of Alzheimer's disease (AD). The mechanism and signaling route, however, remain unclear. This research aimed to investigate the impact of IGF-1 on AD as well as its possible mechanism and signaling route. In this work, intracerebroventricular AAV9-IGF-1 was delivered to APP/PS1 transgenic mice. Following therapy, the Morris water maze and passive avoidance tests were administered to evaluate spatial learning and memory. The elevated plus maze, the open field test, and the sucrose preference test were used to evaluate anxious-depressive-like behavior. Thioflavin S staining was employed to visualize Aß deposition, and ELISA was used to determine the quantities of soluble Aß1-40 and Aß1-42. Transmission electron microscopy was used to view the mitochondrial structure and mitophagy vesicles. The protein expression levels of PINK1, Parkin, and LC3-II/LC3-I were finally determined by Western blotting. AAV9-IGF-1 therapy enhanced spatial learning and memory, relieved anxious-depressive-like behavior impairments, lowered amyloid-ß deposition, and decreased levels of soluble Aß1-40 and Aß1-42. In addition, AAV9-IGF-1 therapy restored mitochondrial integrity and increased the number of mitophagy in transgenic mice expressing APP/PS1. These results indicate that IGF-1 is protective for APP/PS1 mice. The mechanism of the favorable benefits mediated by IGF-1 was connected to an increase in mitophagy, which might give a novel therapy target in the future.

Biological Role and Related Natural Products of SIRT1 in Nonalcoholic Fatty Liver.

Non-alcoholic fatty liver disease(NAFLD) is an umbrella term for a range of diseases ranging from hepatic fat accumulation and steatosis to non-alcoholic steatohepatitis (NASH) in the absence of excessive alcohol consumption and other definite liver damage factors. The incidence of NAFLD has increased significantly in recent years and will continue to grow in the coming decades. NAFLD has become a huge health problem and economic burden. SIRT1 is a member of Sirtuins, a group of highly conserved histone deacetylases regulated by NAD+, and plays a vital role in regulating cholesterol and lipid metabolism, improving oxidative stress, inflammation, and insulin resistance through deacetylating some downstream transcription factors and thus improving NAFLD. Although there are no currently approved drugs for treating NAFLD and some unresolved limitations in developing SIRT1 activators, SIRT1 holds promise as a proper therapeutic target for NAFLD and other metabolic diseases. In recent years, natural products have played an increasingly important role in drug development due to their safety and efficacy. It has been discovered that some natural products may be able to prevent and treat NAFLD by targeting SIRT1 and its related pathways. This paper reviews the mechanism of SIRT1 in the improvement of NALFD and the natural products that regulate NAFLD through SIRT1 and its associated pathways, and discusses the potential of SIRT1 as a therapeutic target for treating NAFLD and the effectiveness of these related natural products as clinical drugs or dietary supplements. These works may provide some new ideas and directions for finding new therapeutic targets for NAFLD and the development of anti-NAFLD drugs with good pharmacodynamic properties.

Abnormal Local Brain Activity and Cognitive Impairments in Young Non-Disabled Patients With Intracerebral Hemorrhage: A Resting-State Functional MRI Study.

BACKGROUND: Resting-state functional MRI (rs-fMRI) has identified static changes of local brain activity among patients with intracerebral hemorrhage (ICH). However, the dynamic and concordance-related characteristics of brain activity remain unclear. PURPOSE: To investigate static, dynamic, and concordance-related features of the regional brain activity of young non-disabled ICH patients. STUDY TYPE: Prospective. SUBJECTS: Thirty-three ICH patients (modified Rankin Scale score ≤2, 21% female, 46.36 ± 6.53) and 33 matched healthy controls (HCs) (21% female, 47.64 ± 6.16). FIELD STRENGTH/SEQUENCE: 3-T, rs-fMRI using gradient echo-planar imaging, T1-weighted imaging. ASSESSMENT: Neuropsychological and rs-fMRI data were acquired from all participants. Amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), voxel-mirrored homotopic connectivity, global signal correlation (GSCorr) and degree centrality (DC), and their dynamic and concordance-related changes with sliding window analysis were calculated based on rs-fMRI data at a whole-brain level. The burden of cerebral small vascular diseases (cSVD) was assessed by cSVD scores. All hemorrhage lesions were delineated on normalized T1 images. STATISTICAL TESTS: Multiple regression models, a voxel-level uncorrected P < 0.001, a cluster-level false discovery rate (FDR) corrected q < 0.05, a re-corrected qFDR <0.05 were considered significant. Pearson or Spearman correlation analyses between fMRI data and neurocognitive performance were performed. RESULTS: Compared to HCs, ICH patients showed significant abnormal changes of ALFF, dynamic ALFF, fALFF, ReHo, dynamic ReHo, GSCorr, DC, and voxel-wise concordance in multiple brain regions mainly including the bilateral cerebellar hemispheres, ipsilesional thalamus, and bilateral middle cingulum gyrus. The ALFF in the cerebellar posterior lobe and thalamus were significantly associated with attention (r = -0.481) and executive function (rho = -0.521) in ICH patients. DATA CONCLUSION: Young non-disabled ICH patients exhibit static, dynamic, and concordance-related alterations of local brain activity, part of which shows associations with cognitive functions. These findings may help comprehensively understand the mechanism of cognitive impairment after ICH. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

[Diosgenin alleviates NAFLD induced by a high-fat diet in rats via mTOR/SREBP-1c/HSP60/MCAD/SCAD signaling pathway].

This study aims to observe the effects of diosgenin on the expression of mammalian target of rapamycin(mTOR), sterol regulatory element-binding protein-1c(SREBP-1c), heat shock protein 60(HSP60), medium-chain acyl-CoA dehydrogenase(MCAD), and short-chain acyl-CoA dehydrogenase(SCAD) in the liver tissue of the rat model of non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin in alleviating NAFLD. Forty male SD rats were randomized into five groups: a control group, a model group, low-(150 mg·kg~(-1)·d~(-1)) and high-dose(300 mg·kg~(-1)·d~(-1)) diosgenin groups, and a simvastatin(4 mg·kg~(-1)·d~(-1)) group. The rats in the control group were fed with a normal diet, while those in the other four groups were fed with a high-fat diet. After feeding for 8 weeks, the body weight of rats in the high-fat diet groups increased significantly. After that, the rats were administrated with the corresponding dose of diosgenin or simvastatin by gavage every day for 8 weeks. The levels of triglyceride(TG), total cholesterol(TC), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were determined by the biochemical method. The levels of TG and TC in the liver were measured by the enzyme method. Oil-red O staining was employed to detect the lipid accumulation, and hematoxylin-eosin(HE) staining to detect the pathological changes in the liver tissue. The mRNA and protein levels of mTOR, SREBP-1c, HSP60, MCAD, and SCAD in the liver tissue of rats were determined by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. Compared with the control group, the model group showed increased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lipid deposition in the liver, obvious hepatic steatosis, up-regulated mRNA and protein expression levels of mTOR and SREBP-1c, and down-regulated mRNA and protein expression levels of HSP60, MCAD, and SCAD. Compared with the model group, the rats in each treatment group showed obviously decreased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lessened lipid deposition in the liver, ameliorated hepatic steatosis, down-regulated mRNA and protein le-vels of mTOR and SREBP-1c, and up-regulated mRNA and protein levels of HSP60, MCAD, and SCAD. The high-dose diosgenin outperformed the low-dose diosgenin and simvastatin. Diosgenin may prevent and treat NAFLD by inhibiting the expression of mTOR and SREBP-1c and promoting the expression of HSP60, MCAD, and SCAD to reduce lipid synthesis, improving mitochondrial function, and promoting fatty acid ß oxidation in the liver.

Metastasis, characteristic, and treatment of breast cancer in young women and older women: A study from the Surveillance, Epidemiology, and End Results registration database.

BACKGROUND: Younger age is an independent risk factor for breast cancer (BC) prognosis, and BC in young women is often considered more aggressive. BC patients with different age and molecular subtypes have different metastasis patterns and survival. Herein, we aim to explore the metastasis patterns, characteristics and treatment methods of young patients with BC, and to compare them with older patients. METHODS: Data of young patients (aged ≤40 years old) and older patients (aged >40 years old) with BC were extracted from the Surveillance, Epidemiology, and End Results (SEER) registration database in 2010-2019 in this retrospective cohort study. Univariate and multivariate competing risk models and proportional hazard models were used to explore the association between different metastasis patterns and treatments and BC prognoses in young and older patients. Kaplan-Meier (KM) curves were drawn to reflect the survival probability of patients with BC who have different metastasis patterns. Also, we performed subgroup analysis of different metastasis patterns to explore the association between different treatments and overall survival (OS)/cancer specific survival (CSS) in patients with BC. The evaluation index was hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Totally, 5,984 patients died, and 92.56% of them died from BC. There were respectively 1,089 young patients and 9,105 older patients, and we found some differences of characteristics and metastasis patterns between them. After adjusting for covariates, young patients who had brain metastasis and multiple sites metastasis seemed to have high risk of both lower OS and CSS. Among older patients with BC, brain metastasis, liver metastasis, and multiple sites metastasis were all positively associated with both lower OS and CSS. In young and older patients, those who not receive radiotherapy or surgery, or received non-surgery combined with radiotherapy seemed to have high risk of both lower OS and CSS. Breast-conserving surgery (BCS) and surgery combined with radiotherapy were associated with higher OS and CSS in young patients, while only older patients received surgery combined with radiotherapy had higher OS and CSS. Results of subgroup analysis indicated that for patients with different metastasis patterns, developing a personalized treatment plan is necessary. CONCLUSIONS: Characteristics of BC between young patients and older patients were different. Clinicians should focus on different metastasis sites and choose appropriate treatments in patients with different ages, which may improve the prognoses.

Acupuncture or moxibustion adjuvant chemotherapy for advanced non-small cell lung cancer: Systematic review and network meta-analysis.

BACKGROUND: To compare the advantages and disadvantages of different acupuncture and moxibustion methods by network meta-analysis, in order to find out the best acupuncture and moxibustion adjuvant chemotherapy scheme of non-small cell lung cancer (NSCLC). METHODS: Randomized controlled trials of acupuncture and moxibustion adjuvant chemotherapy in the treatment of NSCLC were searched in PubMed, Cochrane Library, Web of science, EMbase, China National Knowledge Infrastructure, Wanfang, VIP database and SinoMed. The retrieval time was up to December 03, 2022. ROB2 was used to evaluate publication bias, and Stata16 was used for network meta-analysis. RESULTS: A total of 14 studies involving 921 patients were included. The results of network Meta-analysis showed that the effect of acupuncture combined with chemotherapy was better than that of chemotherapy (RR = 1.28, 95%CI (1.04,1.58), P < .0001). The effect of acupuncture combined with chemotherapy was better than that of chemotherapy in improving KPS score (MD = 9.01, 95%CI (3.35,14.67), P < .0001). The safety of acupuncture combined with chemotherapy (RR = 0.35, 95%CI (0.15,0.83), P < .0001) was better than that of chemotherapy. CONCLUSION: Acupuncture combined with chemotherapy has the best comprehensive effect.

Co-pyrolysis of sewage sludge and waste tobacco stem: Gas products analysis, pyrolysis kinetics, artificial neural network modeling, and synergistic effects.

This research comprehensively investigates the co-pyrolysis of sewage sludge (SS) and waste tobacco stem (WTS). Various SS and WTS ratios (1:0, 0.75:0.25, 0.50:0.50, 0.25:0.75, and 0:1) were tested over a range of heating rates (30 °C to 800 °C). Apparent activation energies were calculated using model-free methods, and the co-pyrolysis mechanism was described with the master plot method. Results suggest that SS and WTS co-pyrolysis follows power-law models (P3, P4). Among blends, S75W25 exhibited optimal synergy, with the lowest activation energy required for the pyrolysis reactions and inhibits CO2 emissions. S75W25's pyrolysis gas primarily contained acids (e.g., ethylxanthogenacetic acid, acetic acid), hydrocarbons (e.g., supraene, cyclopropyl carbinol), and other compounds (e.g., CO2, pyrazine, pyridine, indole). ANN was utilized to forecast the temperature-mass loss relationships in co-pyrolysis, with the optimal model being ANN21, yielding a high correlation coefficient (R2 = 0.99999). This study offers guidance for the efficient utilization of waste SS and WTS.

Selective extraction of phospholipids from human milk using glass fabric modified with zirconium-based metal organic framework.

Phospholipids (PLs) are important and complex trace lipids in milk, which have positive effects on the infants' nervous and immune system development. Herein, a new method for selective extraction of PLs using glass fabric @ MOF-808 was proposed. Based on Lewis acid-base interaction, MOF-808 containing abundant Zr-OH groups was selected as the adsorption body, and glass fabric was used as a substrate to make the adsorbent easy to remove and reuse. The influencing factors such as loading solution, extraction time, eluent and elution time were further investigated. The adsorbent showed high adsorption capacity (3.31-6.54 mg/g for PLs) and good reusability (reused at least five times). The method showed low detection limits (1.61 µg/L - 10.24 µg/L) and quantification limits (5.24 µg/L-51.21 µg/L) for eight classes of PLs. The analysis of PLs in human milk at different lactation stages by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry could obtain up to 206 PLs, indicating that the method has extremely high extraction and anti-interference capabilities. This work is the first time to introduce MOF materials to selectively extract PLs and use glass fabric as a substrate for MOF-808, which has the advantages of easy recovery and high sensitivity. It provides technical support for the discovery of more PL species and has potential applications in phospholipidomics.

The effect of hyperthyroidism on cognitive function, neuroinflammation, and necroptosis in APP/PS1 mice.

BACKGROUND: Increasing evidence has linked the thyroid dysfunction to the pathogenesis of dementia. Evidence from clinical studies has demonstrated that hypothyroidism is related to an increased risk of dementia. But the association of hyperthyroidism with dementia is largely unknown. METHODS: We used the adenovirus containing thyrotropin receptor (TSHR) amino acid residues 1-289 (Ad-TSHR289)-induced Graves' disease (GD) phenotype in Alzheimer's disease (AD) model mice (APP/PS1 mice) to evaluate the effect of hyperthyroidism on the cognitive function and ß-amyloid (Aß) accumulation. RESULTS: GD mice exhibited a stable long-term hyperthyroidism and cognitive deficits. Single Cell RNA-sequencing analysis indicated that microglia function played a critical role in the pathophysiological processes in GD mice. Neuroinflammation and polarization of microglia (M1/M2 phenotype) and activated receptor-interacting serine/threonine protein kinase 3 (RIPK3)/mixed lineage kinase domain-like pseudo-kinase (MLKL)-mediated necroptosis contributed to the pathological process, including Aß deposition and neuronal loss. RIPK3 inhibitor could inhibit GD-mediated Aß accumulation and neuronal loss. CONCLUSIONS: Our findings reveal that GD hyperthyroidism aggravates cognitive deficits in AD mice and induces Aß deposition and neuronal loss by inducing neuroinflammation and RIPK3/MLKL-mediated necroptosis.

Multisite rTMS combined with cognitive training modulates effective connectivity in patients with Alzheimer's disease.

Purpose: To investigate the effective connectivity (EC) changes after multisite repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training (COG). Method: We selected 51 patients with mild or moderate Alzheimer's disease (AD) and delivered 10 Hz rTMS over the left dorsal lateral prefrontal cortex (DLPFC) and the lateral temporal lobe (LTL) combined with COG or sham stimulation for 4 weeks. The selected AD patients were divided into real (real rTMS+COG, n = 11) or sham (sham rTMS+COG, n = 8) groups to undergo neuropsychological assessment, resting-state fMRI, and 3D brain structural imaging before (T0), immediately at the end of treatment (T4), and 4 weeks after treatment (T8). A 2 × 3 factorial design with "time" as the within-subjects factor (three levels: T0, T4, and T8) and "group" as the between-subjects factor (two levels: real and sham) was used to investigate the EC changes related to the stimulation targets in the rest of the brain, as well as the causal interactions among seven resting-state networks based on Granger causality analysis (GCA). Results: At the voxel level, the EC changes from the left DLPFC out to the left inferior parietal lobe and the left superior frontal gyrus, as well as from the left LTL out to the left orbital frontal cortex, had a significant group × time interaction effect. At the network level, a significant interaction effect was identified in the increase in EC from the limbic network out to the default mode network. The decrease in EC at the voxel level and the increase in EC at the network level were both associated with the improved ability to perform activities of daily living and cognitive function. Conclusion: Multisite rTMS combined with cognitive training can modulate effective connectivity in patients with AD, resulting in improved ability to perform activities of daily living and cognitive function.

N6-methyladenosine methylation regulator RBM15 promotes the progression of diabetic nephropathy by regulating cell proliferation, inflammation, oxidative stress, and pyroptosis through activating the AGE-RAGE pathway.

BACKGROUND: Diabetic nephropathy (DN) is a major cause of end-stage renal disease throughout the world, and m6A modification plays a critical role in the progression of DN. We aimed to find m6A-related genes and their regulatory mechanisms in DN. METHODS: The expression levels of four important m6A-related genes (METTL16, RBM15, IGF2BP1, and ALKBH5) were detected by quantitative real-time PCR (RT-qPCR). RBM15 was chosen and its function was explored. The downstream pathway of RBM15 was screened by transcriptome sequencing. The levels of AGE, inflammation, and oxidative stress were determined with enzyme-linked immunosorbent assay, and the expression of AGE-RAGE pathway-related proteins were detected by Western blot (WB). Cell proliferation was assessed by Cell counting Kit-8 (CCK-8). The levels of pyroptosis-related proteins were evaluated by RT-qPCR or WB. RESULTS: METTL16 and RBM15 were up regulated in the mouse model of DN, in which RBM15 was more significant. Silencing RBM15 recovered cell proliferation, reduced the levels of inflammation factors, and inhibited cell pyroptosis in high glucose-induced HK-2 cells. Transcriptome sequencing suggested that the AGE-RAGE pathway might be downstream of RBM15. RBM15 knockdown reduced AGE level and the expression of AGE-RAGE pathway-related proteins. After silencing RBM15, we found that activating the AGE-RAGE pathway inhibited cell proliferation, increased the levels of inflammation factors, promoted oxidative stress, and induced cell pyroptosis in HK-2 cell model of DN. CONCLUSION: The m6A-related gene RBM15 inhibited cell proliferation, promoted inflammation, oxidative stress, and cell pyroptosis, thereby facilitating the progression of DN through the activation of the AGE-RAGE pathway.