Correlation between exosomal PD-L1 and prognosis in patients with cancer: a systematic review and meta-analysis.

BACKGROUND: The predictive role of exosomal programmed cell death ligand l (exoPD-L1) in prognosis has been studied extensively; however, there is still no consensus. METHODS: Three databases, including EMBASE, PubMed, and Web of Science, were searched through January 4, 2024. The pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were used to identify the relationship between circulating exoPD-L1 and prognosis. RESULTS: 15 studies with 1091 patients with cancer were included in this statistical analysis. High exoPD-L1 level was correlated with shorter progression-free survival (PFS) (HR = 2.58, 95% CI: 1.75-3.81) and overall survival (OS) (HR = 1.61, 95% CI: 1.32-1.98). Meanwhile, we found that dynamic upregulation of circulating exoPD-L1 in the early stages of immunotherapy was a favorable factor for prognosis (PFS: HR = 0.34, 95% CI: 0.23-0.51; OS: HR = 0.21, 95% CI: 0.13-0.26). CONCLUSION: Circulating exoPD-L1 may be a valuable prognostic indicator for patients with cancer and monitoring its changes in the early stages of immunotherapy might be used to predict tumor response and clinical outcome. This conclusion may not apply to superficial tumors.

Recurrent COVID-19-related psychotic disorder with neuro-immuno-endocrine dysfunction as a possible underlying mechanism: A case report from China.

Background: SARS-CoV-2, first identified in Wuhan, China, in December 2019, has been gradually spreading worldwide since 2020. The relationship between SARS-CoV-2 infection and psychotic disorders has received much attention, and several studies have described the direct/indirect mechanisms of its effects on the brain, but no mechanism has been found to explain recurrent episodes of COVID-19-related psychotic symptoms. Case: We report the case of an 18-year-old female patient with no family or personal psychotic disorder history with multiple hospital admissions with symptoms such as disorganized speech and behavior, hyperactivity, restlessness, and impulsive aggression during the COVID-19 recovery period. Relevant tests revealed longitudinal changes such as persistent IL-6 and IL-10 elevation, abnormal discharges on EEG, and brain and hippocampal MRI abnormal signals. The patient was treated with antipsychotics, MECT, combination therapy of hormones and antivirals, then discharged after multiple treatment rounds. Conclusion: The case presented here outlines the possibility that the COVID-19 recovery period may be a critical period for acute psychotic episodes and that the patient's recurrent psychotic symptoms may be associated with neuro-immuno-endocrine dysfunction mediated by sustained cytokine synthesis, further causing structural and functional brain damage. Routine psychiatric evaluation and related screening should be performed at all stages of the illness to better identify, prevent, and effectively intervene in psychiatric disorders following COVID-19. Because many outcomes require long-term assessment, a clearer understanding of the impact of the COVID-19 epidemic on mental health is likely to emerge in the future.

Social determinants of health that impact the time to diagnosis and treatment of infertility in Taiwan.

BACKGROUND/PURPOSE: Taiwan is one of the countries with the lowest birth rate in the world. We investigated factors associated with the time to diagnosis and treatment of infertility in Taiwan. METHODS: The study was conducted through an online questionnaire in December 2021. The questionnaire was adapted from a previously published multinational survey, and culture-specific questions were added. 91 infertile patients and 89 partners of patients in Taiwan, aged 20- to 45- year-old, were included. RESULTS: The average duration before diagnosis was 2.9 years, followed by 1.5 years before treatment. Older age at marriage (p = 0.0024), higher education level (P = 0.0001), and a higher gender equality score (p = 0.0031) were associated with earlier diagnosis. Conversely, folk therapy use was linked to later diagnosis (p < 0.0001) and treatment (p < 0.0001). Notably, in the female (p = 0.039) and patient (p = 0.0377) subgroups, a higher gender equality score was associated with a shorter duration of folk therapy. Subjectively, the most frequent factor influencing treatment decision was affordability or lack thereof. The government subsidy for in vitro fertilization led to increased treatment willingness for 46.3% of respondents, and 47.3% reported more likely to pursue earlier treatment. CONCLUSIONS: This study highlights the influence of education, gender equality, folk therapy, and government subsidy on fertility care decisions. To improve the timeliness of infertility healthcare in Taiwan, potential strategies include promoting education, fostering gender equality, providing financial support, and raising awareness on the association between folk therapy and delayed medical care.

LncRNA-SERB promotes vasculogenic mimicry (VM) formation and tumor metastasis in renal cell carcinoma.

A growing body of evidence shows that vasculogenic mimicry (VM) is closely related to the invasion and metastasis of many tumor cells. Although the estrogen receptor (ER) can promote initiation and progression of renal cell carcinoma (RCC), how the downstream biomolecules are involved, and the detailed mechanisms of how ER expression is elevated in RCC remain to be further elucidated. Here, we discovered that long noncoding RNA (LncRNA)-SERB is highly expressed in tumor cells of RCC patients. We used multiple RCC cells and an in vivo mouse model for our study, and results indicated that LncRNA-SERB could boost RCC VM formation and cell invasion in vitro and in vivo. Although a previous report showed that ERß can affect the VM formation in RCC, it is unclear which factor could upregulate ERß. This is the first study to show LncRNA-SERB can be the upstream regulator of ERß to control RCC progression. Mechanistically, LncRNA-SERB may increase ERß via binding to the promoter area, and ERß functions through transcriptional regulation of zinc finger E-box binding homeobox 1 (ZEB1) to regulate VM formation. These results suggest that LncRNA-SERB promotes RCC cell VM formation and invasion by upregulating the ERß/ZEB1 axis and that therapeutic targeting of this newly identified pathway may better inhibit RCC progression.

3-Methyl-4-nitrophenol Exposure Deteriorates Oocyte Maturation by Inducing Spindle Instability and Mitochondrial Dysfunction.

3-methyl-4-nitrophenol (PNMC), a well-known constituent of diesel exhaust particles and degradation products of insecticide fenitrothion, is a widely distributed environmental contaminant. PNMC is toxic to the female reproductive system; however, how it affects meiosis progression in oocytes is unknown. In this study, in vitro maturation of mouse oocytes was applied to investigate the deleterious effects of PNMC. We found that exposure to PNMC significantly compromised oocyte maturation. PNMC disturbed the spindle stability; specifically, it decreased the spindle density and increased the spindle length. The weakened spindle pole location of microtubule-severing enzyme Fignl1 may result in a defective spindle apparatus in PNMC-exposed oocytes. PNMC exposure induced significant mitochondrial dysfunction, including mitochondria distribution, ATP production, mitochondrial membrane potential, and ROS accumulation. The mRNA levels of the mitochondria-related genes were also significantly impaired. Finally, the above-mentioned alterations triggered early apoptosis in the oocytes. In conclusion, PNMC exposure affected oocyte maturation and quality through the regulation of spindle stability and mitochondrial function.

The initial composition and structure of microbial community determined the yield and quality of Baijiu during the spontaneous fermentation / La composición inicial y la estructura de la comunidad microbiana determinaron el rendimiento y la calidad del Baijiu durante la fermentación espontánea

The microbiota during pit mud fermentation is a crucial factor in Baijiu brewing since it determines the yield and flavor. However, the impact of the microbial community during the initial fermentation stage on Baijiu quality remains uncertain. Herein, high-throughput sequencing was employed to investigate the microbial diversities and distribution during Baijiu fermentation in individual pit mud workshops at both initial and late stages. During the initial fermentation stage, the bacterial community exerted a more pronounced effect on Baijiu quality than the fungal community. And the high-yield pit mud workshop exhibited lower richness and evenness, as well as greater Bray-Curtis dissimilarity during Baijiu fermentation. Lactobacillus was the dominant genus and biomarker in high-yield pit mud, and it constituted the only genus within the bacterial association network during the late fermentation stage. Fungal communities tended to maintain a simple association network with selected core species. Based on the correlation network, Rhizopus and Trichosporon were identified as biomarkers in Baijiu fermentation process. Together, Lactobacillus and Rhizopus could serve as bio-indicators for Baijiu quality during the initial fermentation stage. Therefore, these findings provided novel insights into microbiota interactions during fermentation and the impact of initial microbiota on final Baijiu quality.(AU)

Young Plasma Attenuated Chronic Kidney Disease Progression after Acute Kidney Injury by Inhibiting Inflammation in Mice.

In the aged patients suffering from acute kidney injury, the risk for progression to chronic kidney disease and mortality is high. Aging accompanied by glomerulosclerosis, interstitial inflammation, and fibrosis might be one of the underlying mechanisms for vulnerability. In addition to sustained activation of the renin-angiotensin system, persistent chronic inflammation with tertiary lymphoid tissue formation is more common and is associated with disease progression in the aged kidney after acute injury. Based on recent laboratory evidence that young blood can rejuvenate the brain, muscle, and heart, we were intrigued by the possible protective effect of young plasma on acute kidney injury in aged mice. Here, we demonstrated that young plasma from 2-month-old mice could attenuate chronic kidney disease progression in 15-month-old mice subjected to acute kidney injury induced by ischemia-reperfusion. In the aged mice after acute kidney injury, young plasma administration decreased tubulointerstitial injury, fibrosis, and tertiary lymphoid tissue formation in kidneys assessed on day 28 after acute injury despite no significant beneficial effect on injury severity and survival. Mechanistically, young plasma inhibited angiotensin II-activated chemokines in pericytes that were responsible for tertiary lymphoid tissue formation. In summary, our data provide evidence that young plasma attenuates the transition from acute kidney injury to chronic kidney disease in aged mice. The therapeutic potential of young plasma infusion or exchange in the aged patients suffering acute kidney injury needs to be addressed in clinical trials.

A multicenter study on the effects of different methods of disinfecting medical external-use ultrasound probes.

BACKGROUND: Microbial contamination of external-use ultrasound probes is a serious and overlooked issue. We assessed the effects of different methods of disinfecting medical external-use ultrasound probes. METHODS: On-site disinfection experiments were conducted at 10 hospitals; the tips and sides of external-use ultrasound probes were sampled before and after disinfection, and 3 disinfection methods were assessed (use of a new ultraviolet [UV] ultrasound probe disinfector, wiping with ordinary paper towels or cleaning with disinfectant wipes). RESULTS: For the new UV probe disinfector, the median microbial death rates for the tips and sides of the external-use ultrasound probe were 93.67% and 97.50%, respectively, which were higher than those for wiping with paper towels and cleaning with disinfectant wipes (12.50% and 10.00% and 20.00% and 21.42%, respectively); the rates of microorganisms exceeding the standard were 15.0% and 13.3%, respectively, which were lower than those for wiping with paper towels and cleaning with disinfectant wipes (53.3% and 60.0% and 46.7% and 38.3%, respectively). The death rates of different species of microorganisms were high, ranging from 87.5% to 100%. CONCLUSIONS: The new UV ultrasound probe disinfector significantly reduced the risk of potential nosocomial infections according to the low microbial death rate for conventional disinfection methods.

The initial composition and structure of microbial community determined the yield and quality of Baijiu during the spontaneous fermentation.

The microbiota during pit mud fermentation is a crucial factor in Baijiu brewing since it determines the yield and flavor. However, the impact of the microbial community during the initial fermentation stage on Baijiu quality remains uncertain. Herein, high-throughput sequencing was employed to investigate the microbial diversities and distribution during Baijiu fermentation in individual pit mud workshops at both initial and late stages. During the initial fermentation stage, the bacterial community exerted a more pronounced effect on Baijiu quality than the fungal community. And the high-yield pit mud workshop exhibited lower richness and evenness, as well as greater Bray-Curtis dissimilarity during Baijiu fermentation. Lactobacillus was the dominant genus and biomarker in high-yield pit mud, and it constituted the only genus within the bacterial association network during the late fermentation stage. Fungal communities tended to maintain a simple association network with selected core species. Based on the correlation network, Rhizopus and Trichosporon were identified as biomarkers in Baijiu fermentation process. Together, Lactobacillus and Rhizopus could serve as bio-indicators for Baijiu quality during the initial fermentation stage. Therefore, these findings provided novel insights into microbiota interactions during fermentation and the impact of initial microbiota on final Baijiu quality.

Targeted therapy in glomerular diseases.

Targeted therapy has emerged as a more precise approach to treat glomerular diseases, focusing on specific molecular or cellular processes that contribute to disease development or progression. This approach complements or replaces traditional immunosuppressive therapy, optimizes supportive care, and provides a more personalized treatment strategy. In this review, we summarize the evolving understanding of pathogenic mechanisms in immune-mediated glomerular diseases and the developing targeted therapies based on these mechanisms. We begin by discussing pan-B-cell depletion, anti-CD20 rituximab, and targeting B-cell survival signaling through the BAFF/APRIL pathway. We also exam specific plasma cell depletion with anti-CD38 antibody. We then shift our focus to complement activation in glomerular diseases, which is involved in antibody-mediated glomerular diseases, such as IgA nephropathy, membranous nephropathy, ANCA-associated vasculitis, and lupus nephritis. Non-antibody-mediated complement activation occurs in glomerular diseases, including C3 glomerulopathy, complement-mediated atypical hemolytic uremic syndrome, and focal segmental glomerulosclerosis. We discuss specific inhibition of terminal, lectin, and alternative pathways in different glomerular diseases. Finally, we summarize current clinical trials targeting the final pathways of various glomerular diseases, including kidney fibrosis. We conclude that targeted therapy based on individualized pathogenesis should be the future of treating glomerular diseases.

Effects of rotation and Bacillus on the changes of continuous cropping soil fungal communities in American ginseng.

The continuous cropping obstacle is the main factor in leading to difficulty in American ginseng replanting. The dormant microbiota in the soil may be the cause of American ginseng disease and eventually caused continuous cropping obstacles, but there are few studies on the dynamic changes of soil microenvironment after American ginseng planting. In this study, we tracked short-term variation in physicochemical properties, enzyme activities, and fungal communities over time-series in soils with continuous cropping obstacle under crop rotation and probiotic Bacillus treatments. Furthermore, we examined the relationships between the important fungal compositions and the soil properties. The results showed that sucrase, cellulase, urease and acid phosphatase activities were significantly increased, while catalase and dehydrogenase were decreased with treatments time. Rotation treatment significantly affected the diversity, dissimilarity degree and species distribution of soil fungal community with continuous cropping obstacle over a short-term. Moreover, beneficial fungal biomarkers such as Cladorrhinum, Oidiodendron, and Mariannaea were accumulated at 48 h under rotation treatments. Almost all fungal biomarkers were negatively correlated with hydrolases and positively correlated with oxidoreductases and acid phosphatase under crop rotation treatments. This study suggested that compared to probiotic Bacillus, crop rotation can significantly affect soil fungal community structure, especially the enrichment of specific potentially beneficial fungal species. Our findings provide a scientific basis for understanding the dynamic changes of fungal communities and soil properties with continuous cropping obstacle of American ginseng in initial stage of soil improvement.

Analysis on Bacterial Distribution and Change of Drug Resistance Rate in ICUs Across Southwest China from 2018 to 2022.

Purpose: To analyze the distribution of bacteria and their drug resistance changes in Intensive Care Units (ICUs) across Southwest China from 2018 to 2022 and establish the antibiogram in this region to provide a basis for early empirical antimicrobial use. Methods: Non-repetitive pathogens isolated from 109 member units with qualified data were obtained from the Antimicrobial Resistance Surveillance System in Sichuan Province, southwest China. The results obtained were interpreted with reference to CLSI M100-31th, and analyzed with WHONET 5.6 software. Results: A total of 46,728 clinical isolates in ICUs were collected from 2018 to 2022, of which gram-negative organisms accounted for 76.1%, and gram-positive were 23.9%. The top 5 were Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus, respectively. From 2018 to 2022, the resistance rates of Klebsiella pneumoniae to imipenem and meropenem changed from 14.5% and 17.8% to 14.0% and 14.4%, showing a steady downward trend. Escherichia coli was always highly sensitive to carbapenems, with a total resistance rate of 3.8%. Among non-fermented gram-negative bacteria, the resistance rates of Pseudomonas aeruginosa to imipenem and meropenem decreased significantly, changed from 25.3% and 22.9% in 2018 to 20.0% and 15.1% in 2022. However, Acinetobacter baumannii showed high resistance rates of 76.2% and 76.9% to imipenem and meropenem, respectively. MRSA and MRCNS accounted for 31.7% and 82.7%, respectively. No vancomycin and linezolid-resistant Staphylococcus aureus was isolated. Enterococcus faecalis maintained high activity to vancomycin, teicoplanin, and linezolid; no vancomycin or teicoplanin-resistant Enterococcus faecium strains were detected. Conclusion: From 2018 to 2022, the isolated bacteria in ICU were mainly gram-negative bacteria, and the growth of some multidrug-resistant bacteria was effectively controlled. All levels of medical institutions should continue to strengthen bacterial resistance surveillance, promote the establishment of antimicrobial stewardship program, and enhance restrictions on outpatient antimicrobial use.

A novel coagulation-related lncRNA predicts the prognosis and immune of clear cell renal cell carcinoma.

Renal cell cancer is associated with the coagulation system. Long non-coding RNA (lncRNA) expression is closely associated with the development of clear cell renal cell carcinoma (ccRCC). The aim of this study was to build a novel lncRNA model to predict the prognosis and immunological state of ccRCC. The transcriptomic data and clinical data of ccRCC were retrieved from TCGA database, subsequently, the lasso regression and lambda spectra were used to filter prognostic lncRNAs. ROC curves and the C-index were used to confirm the predictive effectiveness of this model. We also explored the difference in immune infiltration, immune checkpoints, tumor mutation burden (TMB) and drug sensitivity between the high- and low-risk groups. We created an 8 lncRNA model for predicting the outcome of ccRCC. Multivariate Cox regression analysis showed that age, tumor grade, and risk score are independent prognostic factors for ccRCC patients. ROC curve and C-index revealed the model had a good performance in predicting prognosis of ccRCC. GO and KEGG analysis showed that coagulation related genes were related to immune response. In addition, high risk group had greater TMB level and higher immune checkpoints expression. Sorafenib, Imatinib, Pazopanib, and etoposide had higher half maximal inhibitory concentration (IC50) in the high risk group whereas Sunitinib and Bosutinib had lower IC50. This novel coagulation-related long noncoding RNAs model could predict the prognosis of patients with ccRCC, and coagulation-related lncRNA may be connected to the tumor microenvironment and gene mutation of ccRCC.

Emergence of KPC-134, a KPC-2 variant associated with ceftazidime-avibactam resistance in a ST11 Klebsiella pneumoniae clinical strain.

The emergence of various new Klebsiella pneumoniae carbapenemase (KPC) variants leading to ceftazidime-avibactam treatment failure is a new challenge in current clinical anti-infection treatment. Here, we report a ceftazidime-avibactam-resistant K. pneumoniae 1072-2 clinical strain carrying a novel KPC variant, KPC-134, which differs from KPC-2 by both single mutation (D178A) and 8-amino acid insertions (asp-asp-asn-arg-ala-pro-asn-lys). The results of antimicrobial susceptibility testing showed that the isolate was resistant to meropenem (MIC = 4 mg/L), ceftazidime (MIC ≥ 32 mg/L), cefepime (MIC ≥128 mg/L), aztreonam (MIC ≥128 mg/L), and ceftazidime-avibactam (MIC ≥128 mg/L) but sensitive to imipenem (MIC = 0.5 mg/L), imepenem-relebactam (MIC = 0.5 mg/L), meropenem-vaborbactam (MIC = 2 mg/L), and aztreonam-avibactam (MIC = 4 mg/L). The plasmid containing blaKPC-134 was isolated from K. pneumoniae, and the blaKPC-134 gene was cloned into plasmid pHSG398 and transformed into an Escherichia coli DH5α to observe changes in antimicrobial resistance. The results indicated that the transformant was positive for blaKPC-134 and increased MICs of ceftazidime-avibactam, ceftazidime, cefepime, and aztreonam by 512-fold, 256-fold, 16-fold, and 4-fold, respectively, compared with the recipient. The results of third-generation sequencing showed that the blaKPC-134 gene was carried by a 133,789 bp IncFII-IncR plasmid, and many common resistance genes (including blaCTX-M-65, blaTEM-1B, blaSHV-12, rmtB, and catB4) along with the IS26, tnpR, ISkpn8, ISkpn6-like, and Tn1721 elements were identified. IMPORTANCE The emergence of various new KPC variants leading to ceftazidime-avibactam treatment failure is a new challenge for clinical anti-infection treatment. Here, we describe the characterization of a ceftazidime-avibactam-resistant blaKPC-134-positive Klebsiella pneumoniae clinical strain for the first time. K. pneumoniae bearing with KPC variant often mislead clinical anti-infection treatment because of their unique antimicrobial susceptibility profile and the tendency of conventional carbapenemase assays to give false negative results. Therefore, timely identification of KPC variants and effective anti-infective therapy are key to saving infected patients.

TET Family Members Are Integral to Porcine Oocyte Maturation and Parthenogenetic Pre-Implantation Embryogenesis.

The ten-eleven translocation (TET) enzyme family, which includes TET1/2/3, participates in active DNA demethylation in the eukaryotic genome; moreover, TET1/2/3 are functionally redundant in mice embryos. However, the combined effect of TET1/2/3 triple-gene knockdown or knockout on the porcine oocytes or embryos is still unclear. In this study, using Bobcat339, a specific small-molecule inhibitor of the TET family, we explored the effects of TET enzymes on oocyte maturation and early embryogenesis in pigs. Our results revealed that Bobcat339 treatment blocked porcine oocyte maturation and triggered early apoptosis. Furthermore, in the Bobcat339-treated oocytes, spindle architecture and chromosome alignment were disrupted, probably due to the huge loss of 5-hydroxymethylcytosine (5hmC)and concurrent increase in 5-methylcytosine (5mC). After Bobcat339 treatment, early parthenogenetic embryos exhibited abnormal 5mC and 5hmC levels, which resulted in compromised cleavage and blastocyst rate. The mRNA levels of EIF1A and DPPA2 (ZGA marker genes) were significantly decreased, which may explain why the embryos were arrested at the 4-cell stage after Bobcat339 treatment. In addition, the mRNA levels of pluripotency-related genes OCT4 and NANOG were declined after Bobcat339 treatment. RNA sequencing analysis revealed differentially expressed genes in Bobcat339-treated embryos at the 4-cell stage, which were significantly enriched in cell proliferation, cell component related to mitochondrion, and cell adhesion molecule binding. Our results indicated that TET proteins are essential for porcine oocyte maturation and early embryogenesis, and they act by mediating 5mC/5hmC levels and gene transcription.

FDC-SP as a diagnostic and prognostic biomarker and modulates immune infiltrates in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC), one of the top 10 causes of cancer death, is responsible for more than 90% of all cases of primary renal cancer worldwide. Follicular dendritic cell-secreted protein (FDC-SP) specifically binds to activated B cells and regulates the generation of antibodies. It is also thought to promote cancer cell invasion and migration, which could help with tumor metastases. This study aimed to assess the efficacy of FDC-SP in the diagnosis and prognosis of RCC and to investigate the relationship between immune infiltration in RCC and these outcomes. RESULTS: RCC tissues had significantly higher levels of FDC-SP protein and mRNA than normal tissues. The high level of FDC-SP expression was linked to the T stage, histological grade, pathological stage, N stage, M stage, and OS event. Functional enrichment analysis identified the major pathways that were enriched as immune response regulation, complement, and coagulation. Immunological checkpoints and immune cell infiltration were observed to substantially correlate with the levels of FDC-SP expression. FDC-SP expression levels showed the ability to precisely distinguish high-grade or high-stage renal cancer (area under the curve (AUC) = 0.830, 0.722), and RCC patients with higher FDC-SP expression levels had worse prognoses. The AUC values for one-, two-, and five-year survival rates were all greater than 0.600. Moreover, the FDC-SP expression is an independent predictive biomarker of OS in RCC patients. CONCLUSION: FDC-SP may be a prospective therapeutic target in RCC as well as a possible diagnostic and prognostic biomarker associated with immune infiltration.

Inhibitory effect of chikusetsusaponin IVa on proliferation of triple negative breast cancer cells / 药学学报

Chikusetsusaponin IVa (CsIVa) is a natural active monomer of triterpene saponins in the Chinese herbal medicine of Panax japonicus, which has anti-inflammatory, anti-tumor and other effects. However, its function and mechanism in triple negative breast cancer (TNBC) remain unclear. This study investigated the inhibitory effect and mechanisms of CsIVa on the proliferation of triple negative breast cancer cell line MDA-MB-231. In this study, we found that CsIVa could significantly inhibit the proliferation of MDA-MB-231 cells and eliminate its potential toxic effect on normal breast cells (MCF-10A). The transcriptome sequencing results showed that the inhibition of proliferation of MDA-MB-231 cells by CsIVa was closely related to cell cycle and the pathway regulating cell cycle. Further studies confirmed that CsIVa blocked the cell cycle in G2/M phase by down-regulating the expression of cyclin dependent kinase 1 (CDK1), cyclin B1 and up-regulating the expression of cyclin dependent kinase inhibitor 1A (p21). Moreover, CsIVa can block cell cycle through inhibiting PI3K/AKT signal pathway. In conclusion, CsIVa regulates the expression of cell cycle related proteins (p21, CDK1, cyclin B1) via inhibiting the activity of PI3K/AKT signaling pathway, blocks TNBC cell cycle, and thus exerts its anti-tumor activity.

Timing of systemic resistance induced by local exogenous ABA application within clonal network of stoloniferous herb Centella asiatica subjected to low water availability.

Resistance traits of plants can be activated both at the damaged site and undamaged parts. Systemic resistance induced by local exogenous abscisic acid (ABA) application alleviated negative effect of low water availability on growth performance of clonal plant. However, timing of systemic resistance was poorly understood. Timing of systemic resistance refers to its activation and decay time within clonal network. Clonal fragment of Centella asiatica with four successive ramets (including first-oldest, second-older, third-old and fourth-young ramets) subjected to low water availability (20% soil moisture content) was used to explore effects of local exogenous ABA application on the timing of resistance activation and decay. Systemic resistance activated by local exogenous ABA application after 4 days remained at least 28 days. Compared with control, biomass accumulation of whole clonal fragment, root biomass and ratio of belowground to aboveground biomass significantly increased by local exogenous ABA application after 28 days. It is suggested that rapid activation and delay of resistance response induced by local exogenous ABA application within clonal network may improve fitness of clonal plant subjected to abiotic stress.

Task-related neural activation abnormalities in patients with remitted major depressive disorder: A coordinate-based meta-analysis.

Major depressive disorder (MDD) patients demonstrate abnormal neural activation even after complete remission. Many task-related functional magnetic resonance imaging (fMRI) studies have focused on changes in brain function in individuals with remitted MDD (rMDD). We conducted a meta-analysis of these studies to explore differences in brain activation between patients with rMDD and healthy controls (HCs). Our meta-analysis included 13 studies, encompassing 18 experiments, 304 rMDD patients and 321 HCs. Patients with rMDD showed increased neural activation in the left inferior parietal gyrus and right fusiform gyrus and decreased neural activation in the left superior frontal gyrus, right middle temporal gyrus and right Heschl gyrus. Meta-regression analysis revealed that patient age and the number of depressive episodes were negatively associated with brain activity in the left superior frontal gyrus. Our findings suggest abnormal brain function, especially in areas involved in cognitive function, emotion regulation and perception, in rMDD patients; alterations of these regions may be the primary or secondary neurophysiological mechanisms underlying MDD and provide potential neuroimaging targets for early screening.

Mechanically Strong and Thermally Stable Chemical Cross-Linked Polyimide Aerogels for Thermal Insulator.

High-performance thermal insulating materials are highly desirable in several fields, especially for thermal insulation of buildings to reduce energy consumption. Owing to the remarkable thermal stability, high porosity, low density, and outstanding mechanical features, polyimide (PI) aerogels have attracted great attention. In this work, chemical cross-linked PI (CCPI) aerogels were fabricated via freeze-drying and thermal imidization, which possess outstanding mechanical properties, good thermal stability, and excellent thermal insulation characteristics. The chemically cross-linked structure can effectively inhibit shrinkage, while retaining the structural integrity, resulting in the lower density and lower shrinkage of the materials. In this paper, completely imidized and highly cross-linked polyimide aerogels were synthesized by using p-phenylenediamine (PDA), 3,3',4,4'-biphenyltetracarboxylic dianhydride (BPDA), and the cross-linker 2,3,6,7,14,15-hexaaminotriptycene (HMT). The CCPI aerogels with excellent properties, such as covalently cross-linked chemical structure, low density (0.069 g/cm3), low volume shrinkage (10%), high decomposition temperature (Td5% = 587 °C), and low thermal conductivity (25 mW m-1K-1) are in high demand in the field of thermal insulation. This work furnishes a new method for the development of polymer-based thermal insulation materials for various prospective applications.