Clinical Analysis and Mental Health Survey of Hemophilia Carriers: a Cross-sectional Study.

OBJECTIVE: Hemophilia carriers (HCs), who are heterozygous for mutations in the clotting factor VIII/clotting factor IX gene (F8 or F9), may have a wide range of clotting factor levels, from very low, similar to afflicted males, to the upper limit of normal, and may experience mental health issues. The purpose of this study was to provide genetic information on mothers of hemophilia patients and to understand the clotting factor activity and phenotype of HCs. Additionally, we aimed to investigate the mental health status of HCs in China. METHODS: A total of 127 hemophilia mothers, including 93 hemophilia A (HA) mothers and 34 hemophilia B (HB) mothers, were enrolled in this study. Long distance PCR, multiplex PCR, and Sanger sequencing were used to analyze mutations in F8 or F9. Coagulation factor activity was detected by a one-stage clotting assay. The Symptom Checklist 90 (SCL-90, China/Mandarin version) was given to HCs at the same time to assess their mental health. RESULTS: A total of 90.6% of hemophilia mothers were diagnosed genetically as carriers, with inversion in intron 22 and missense mutations being the most common mutation types in HA and HB carriers, respectively. The median clotting factor level in carriers was 0.74 IU/mL (ranging from 0.09 to 1.74 IU/mL) compared with 1.49 IU/mL (ranging from 0.93 to 1.89 IU/mL) in noncarriers, of which 14.3% of HCs had clotting factor levels of 0.40 IU/mL or below. A total of 53.8% (7/13) of HA carriers with low clotting factor levels (less than 0.50 IU/mL) had a history of bleeding, while none of the HB carriers displayed a bleeding phenotype. The total mean score and the global severity index of the SCL-90 for surveyed HCs were 171.00 (±60.37) and 1.78 (±0.59), respectively. A total of 67.7% of the respondents had psychological symptoms, with obsessive-compulsive disorder being the most prevalent and severe. The pooled estimates of all nine factors were significantly higher than those in the general population (P<0.05). CONCLUSIONS: The detection rate of gene mutations in hemophilia mothers was 90.6%, with a median clotting factor level of 0.74 IU/mL, and 14.3% of HCs had a clotting factor level of 0.40 IU/mL or below. A history of bleeding was present in 41.2% of HCs with low clotting factor levels (less than 0.50 IU/mL). Additionally, given the fragile mental health status of HCs in China, it is critical to develop efficient strategies to improve psychological well-being.

Exploring the impact of high-altitude de-acclimatization on renal function: The roles of oxidative and endoplasmic reticulum stress in rat models.

BACKGROUND: High-altitude de-acclimatization (HADA) significantly impacts physiological functions when individuals acclimatize to high altitudes return to lower altitudes. This study investigates HADA's effects on renal function and structure in rats, focusing on oxidative and endoplasmic reticulum stress as potential mechanisms of renal injury. OBJECTIVE: To elucidate the pathophysiological mechanisms of renal damage in HADA and evaluate the efficacy of antioxidants Vitamin C (Vit C) and tauroursodeoxycholic acid (TUDCA) in mitigating these effects. METHODS: 88 male Sprague-Dawley rats were randomly divided into a control group, a high-altitude (HA) group, a high-altitude de-acclimatization (HADA) group, and a treatment group. The control group was housed in a sea level environment (500 m), while the HA, HADA, and treatment groups were placed in a simulated high-altitude chamber (5000 m) for 90 days. After this period, the HA group completed the modeling phase; the HADA group was further subdivided into four subgroups, each continuing to be housed in a sea level environment for 3, 7, 14, and 30 days, respectively. The treatment group was split into the Vit C group, the TUDCA group, and two placebo groups, receiving medication for 3 consecutive days, once daily upon return to the sea level. The Vit C group received 100 mg/kg Vit C solution via intravenous injection, the TUDCA group received 250 mg/kg TUDCA solution via intraperitoneal injection, and the placebo groups received an equivalent volume of saline similarly. Serum, urine, and kidney tissues were collected immediately after the modeling phase. Renal function and oxidative stress levels were assessed using biochemical and ELISA methods. Renal histopathology was observed with H&E, Masson's trichrome, PAS, and PASM staining. Transmission electron microscopy was used to examine the ultrastructure of glomeruli and filtration barrier. TUNEL staining assessed cortical apoptosis in the kidneys. Metabolomics was employed for differential metabolite screening and pathway enrichment analysis. RESULTS: Compared to the control and HA groups, the HADA 3-day group (HADA-3D) exhibited elevated renal function indicators, significant pathological damage, observable ultrastructural alterations including endoplasmic reticulum expansion and apoptosis. TUNEL-positive cells significantly increased, indicating heightened oxidative stress levels. Various differential metabolites were enriched in pathways related to oxidative and endoplasmic reticulum stress. Early intervention with Vit C and TUDCA markedly alleviated renal injury in HADA rats, significantly reducing the number of apoptotic cells, mitigating endoplasmic reticulum stress, and substantially lowering oxidative stress levels. CONCLUSION: This study elucidates the pivotal roles of oxidative and endoplasmic reticulum stress in the early-stage renal injury in rats undergoing HADA. Early intervention with the Vit C and TUDCA significantly mitigates renal damage caused by HADA. These findings provide insights into the pathophysiological mechanisms of HADA and suggest potential therapeutic strategies for its future management.

Enhanced copper removal by magnesium modified biochar derived from Alternanthera philoxeroides.

Adsorption processes are being widely used by various researchers for the removal of heavy metals from waste streams and biochar has been frequently used as an adsorbent. In this study, a MgO-loaded biochar derived from Alternanthera philoxeroides (MAPB) was synthesized for the removal of Cu(II). Compared with other biochar absorbents, MAPB showed a relatively slow adsorption kinetics, but an effective removal of Cu(II) with a maximum sorption capacity of 1, 238 mg/g. The adsorption mechanism of Cu(II) by MAPB was mainly controlled by chemical precipitation as Cu2(OH)3NO3, complexation and ion replacement. Fixed bed column with MAPB packed in same dosage (1, 000 mg) and different bed depth (1.3, 2.6 and 3.9 cm) showed that the increased of bed depth by mixing MAPB with quartz sand could increase the removal of Cu(II). The fitted breakthrough (BT) models showed that mixing MAPB with support media could reduce the mass transfer rate, increase the dynamic adsorption capacity and BT time. Therefore, MAPB adsorbent act as a highly efficient long-term adsorbent for Cu(II) contaminated water treatment may have great ecological and environmental significance.

Role of increased IGFBP2 in trophoblast cell proliferation and recurrent spontaneous abortion development: A pilot study.

Recurrent spontaneous abortion (RSA) is a serious condition that adversely affects women's health. Differentially expressed proteins (DEPs) in plasma of patients experiencing RSA is helpful to find new therapeutic targets and identified with mass spectrometry. In 57 DEPs, 21 were upregulated and 36 were downregulated in RSA. Gene ontology analyses indicated that identified DEPs were associated with cell proliferation, including significantly downregulated insulin-like growth factor binding protein 2 (IGFBP2). Immunohistochemical result using clinical decidual tissues also showed that IGFBP2 expression was significantly decreased in RSA trophoblasts. Cell proliferation assay indicated that IGFBP2 treatment increased the proliferation and mRNA expressions of PCNA and Ki67 in trophoblast cells. Transcriptome sequencing experiments and Kyoto Encyclopedia of Genes and Genomes analyses revealed that gene expression for components in PI3K-Akt pathway in trophoblasts was significantly upregulated following IGFBP2 treatment. To confirm bioinformatics findings, we did cell-based experiments and found that treatment of inhibitors for insulin-like growth factor (IGF)-1 receptor-PI3K-Akt pathway significantly reduced IGFBP2-induced trophoblast cell proliferation and mRNA expressions of PCNA and Ki67. Our findings suggest that IGFBP2 may increase trophoblast proliferation through the PI3K-Akt signaling pathway to affect pregnancy outcomes and that IGFBP2 may be a new target for future research and treatment of RSA.

Establishment of Hepatocarcinoma in BALB/c-nu Mice and Investigation of the Therapeutic Effect of the Sanleng Jiashen Formula.

The lethality of liver cancer and the resistance to chemical drugs have forced the search for effective prescriptions of traditional herbs for liver cancer. Animal models that are repeatable, easy to manipulate, and highly mimic the pathophysiological processes of liver cancer are the prerequisite for the successful screening of effective drug candidates. Meanwhile, reliable drug efficacy evaluation indicators and means are also the guarantee of anti-liver cancer drug research and development. Sanleng Jiashen formula, a representative prescription of traditional Chinese medicine containing Sparganium stoloni erum, Buch. -Ham. (Sanleng), Panax ginseng C. A. Mey. (ginseng), Rheum officinale Baill. (rhubarb), and Ligusticum chuanxiong Hort. (Chuanxiong), is prescribed to nourish the liver and clear heat, remove toxins, and promote blood circulation to treat liver cancer. This experimental protocol describes the preparation of lyophilized Sanleng Jiashen formula and the establishment process of in-situ liver cancer in BALB/c-nu mice. Histopathological staining, immunohistochemical detection of cancer markers, in vivo imaging of mice, and chick embryo chorioallantoic membrane test were used to explore the inhibition and anti-angiogenesis effect of Sanleng Jiashen formula on malignant proliferation of liver cancer tissue. The data show that the Sanleng Jiashen formula can effectively resist the malignant proliferation of liver cancer tissue, which is manifested by reduced tumor mass volume, improved pathological damage, and lower levels of the cancer marker ki67. The superior inhibition of angiogenesis also suggests that the Sanleng Jiashen formula may have the potential to treat and prevent the progression and deterioration of liver cancer. The whole experimental scheme shows a comprehensive process of traditional Chinese medicine components in the treatment of mouse liver cancer, which provides a reference for the establishment and optimization of a liver cancer model, as well as the research and development of drugs to prevent and treat liver cancer.

Features of thromboelastogram in populations exposed to or transferring from high altitude.

Background: Thromboelastogram (TEG) is an effective indicator that monitors the dynamic changes of blood coagulation in real-time. It still remains controversial about the performance and influence of coagulation at high altitude. The present study intends to describe comprehensively the clinical features of TEG in populations exposed to or transferring from high altitude. Methods: Two groups were recruited in the present study. Group A included young males who worked at high-altitude (4888 m or 5418 m) areas for some time, while Group B included young males who had recently returned from high-altitude (4888 m or 5418 m) areas. Medical examinations were performed using portable devices. Spearman's test was used to evaluate the correlations between thromboelastogram (TEG) variables and other variables. Logistic regression analysis was used to analyze the factors affecting various abnormal TEG variables. Results: A total of 51 adult males were included in the two groups. Significantly increased reaction time (R) and decreased maximum amplitude (MA) were found in group B (P < 0.05). No significant differences were observed in the comparisons of K and angle between the two groups. Various TEG variables were identified to be correlated with different coagulation and biochemical variables. Logistic regression analysis demonstrated that abnormal R was independently associated with direct bilirubin, and abnormal K was independently associated with the platelet count in Group A (P < 0.05). However, none of the factors were independently associated with abnormal TEG variables in Group B. Conclusion: Populations exposed to or transferring from high altitudes are characterized by different TEG characteristics. Our findings give a comprehensive description of the complex interaction between TEG indexes, coagulation dynamics, and hematological parameters, which can help guide the development of appropriate medical approaches tailored to the unique needs of these populations.

Sex-Specific Association of Body Mass Index with Hippocampal Subfield Volume and Cognitive Function in Non-Demented Chinese Older Adults.

Recent research suggests a possible association between midlife obesity and an increased risk of dementia in later life. However, the underlying mechanisms remain unclear. Little is known about the relationship between body mass index (BMI) and hippocampal subfield atrophy. In this study, we aimed to explore the associations between BMI and hippocampal subfield volumes and cognitive function in non-demented Chinese older adults. Hippocampal volumes were assessed using structural magnetic resonance imaging. Cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A total of 66 participants were included in the final analysis, with 35 females and 31 males. We observed a significant correlation between BMI and the hippocampal fissure volume in older females. In addition, there was a negative association between BMI and the RBANS total scale score, the coding score, and the story recall score, whereas no significant correlations were observed in older males. In conclusion, our findings revealed sex-specific associations between BMI and hippocampal subfield volumes and cognitive performance, providing valuable insights into the development of effective interventions for the early prevention of cognitive decline.

Extraperitonealization of the ileal conduit decreases the risk of parastomal hernia: A single-center, randomized clinical trial.

Parastomal hernia (PSH) is a common complication in patients receiving ileal conduit urinary diversion after radical cystectomy. In this randomized controlled clinical trial, we validate our previous finding that extraperitonealization of ileal conduit decreases incidence of PSH. In total, 104 consecutive patients undergoing radical cystectomy at Sun Yat-sen University Cancer Center are randomized 1:1 to receive either modified (extraperitonealized) ileal conduit (n = 52) or conventional ileal conduit (n = 52). Primary endpoint is incidence of radiological PSH during follow-up. Incidence of radiological PSH is lower in the modified group than in the conventional group (11.5% vs. 28.8%; p = 0.028) after a median follow-up of 32 months, corresponding to a hazard ratio of 0.374 (95% confidence interval: 0.145-0.965, p = 0.034) in the modified conduit group. The results support our previous finding that extraperitonealization of the ileal conduit is effective for reducing risk of PSH in patients receiving ileal conduit diversion.

Immune characteristics analysis and construction of a four-gene prognostic signature for lung adenocarcinoma based on estrogen reactivity.

Lung adenocarcinoma (LUAD) is a common type of malignant tumor with poor prognosis and high mortality. In our previous studies, we found that estrogen is an important risk factor for LUAD, and different estrogen statuses can predict different prognoses. Therefore, in this study, we constructed a prognostic signature related to estrogen reactivity to determine the relationship between different estrogen reactivities and prognosis. We downloaded the LUAD dataset from The Cancer Genome Atlas (TCGA) database, calculated the estrogen reactivity of each sample, and divided them into a high-estrogen reactivity group and a low-estrogen reactivity group. The difference in overall survival between the groups was significant. We also analyzed the status of immune cell infiltration and immune checkpoint expression between the groups. We analyzed the differential gene expression between the groups and screened four key prognostic factors by the least absolute shrinkage and selection operator (LASSO) regression and univariable and multivariable Cox regression. Based on the four genes, a risk signature was established. To a certain extent, the receiver operating characteristic (ROC) curve showed the predictive ability of the risk signature, which was further verified using the GSE31210 dataset. We also determined the role of estrogen in LUAD using an orthotopic mouse model. Additionally, we developed a predictive nomogram combining the risk signature with other clinical characteristics. In conclusion, our four-gene prognostic signature based on estrogen reactivity had prognostic value and can provide new insights into the development of treatment strategies for LUAD.

Altered auditory processes pattern predicts cognitive decline in older adults: different modalities with aging.

Background: Cohort studies have shown that older adults with hearing impairment as assessed by self-report or behavioral measures are at higher risk of developing dementia many years later. A fine-grained examination of auditory processing holds promise for more effective screening of older adults at risk of cognitive decline. The auditory mismatch negativity (MMN) measure enables one to gain insights into the neurobiological substrate of central auditory processing. We hypothesized that older adults showing compromised indexes of MMN at baseline would exhibit cognitive decline at the one-year follow-up. Methods: We performed cognitive evaluations with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS; Form A and Form B) in 108 community-dwelling older adults and acquired EEG via the classic passive auditory oddball paradigm at baseline and 12-month follow-up. Results: The results showed that young-old adults with future cognitive decline showed a decrease in MMN peak amplitude, accompanied by a forward-shifting latency, whereas in older adults it showed a delay in MMN latency, and unchanged MMN peak amplitude at midline electrodes (Fz, FCz and Cz). Furthermore, the peak amplitude of the MMN decreases with age in older adults aged 70-80 years rather than 60-70 years or > 80 years. Conclusion: The altered MMN model exists in different aging stages and it's a promising electrophysiological predictor of cognitive decline in older adults. In addition, further research is needed to determine the neural mechanisms and potential implications of the accelerated decline in MMN in older adults.

Immunoglobulin G inhibits glucocorticoid-induced osteoporosis through occupation of FcγRI.

Glucocorticoid-induced osteoporosis (GIOP) is a severe and common complication of long-term usage of glucocorticoids (GCs) and lacks of efficient therapy. Here, we investigated the mechanism of anti-inflammation effect and osteoclastogenesis side effect of GCs and immunoglobulin G (IgG) treatment against GIOP. GCs inhibited SLE IgG-induced inflammation, while IgG inhibited GCs-induced osteoclastogenesis. FcγRI and glucocorticoid receptor (GR) were found directly interacted with each other. GCs and IgG could reduce the expression of FcγRI on macrophages. The deficiency of FcγRI affected osteoclastogenesis by GCs and systemic lupus erythematosus (SLE) IgG-induced inflammation. Also, IgG efficiently reduced GIOP in mice. These data showed that GCs could induce osteoporosis and inhibit IgG-induced inflammation through FcγRI while IgG efficiently suppressed osteoporosis induced by GCs through FcγRI. Hence, our findings may help in developing a feasible therapeutic strategy against osteoporosis, such as GIOP.

Effects of oral intake fruit or fruit extract on skin aging in healthy adults: a systematic review and Meta-analysis of randomized controlled trials.

Background: In recent years, oral various fruits or supplements of fruits natural extracts have been reported to have significant anti-aging effects on the skin (1, 2), However, despite many studies on this topic, there is often no clear evidence to support their efficacy and safety. In this paper, we present a comprehensive review and Meta-analysis of the evidence for the safety and efficacy of oral fruits and fruits extracts in improving skin aging. Methods: Four databases, Pubmed, Embase, Web of Science, and Cochrane Library (CENTRAL), were searched for relevant literature from 2000-01 to 2023-03. Seven randomized controlled trials (RCTs) of fruit intake or fruit extracts associated with anti-skin aging were screened for Meta-analysis. Results: Compared to placebo, oral intake of fruit or fruit extracts showed significant statistical differences in skin hydration and transepidermal water loss (TEWL), with a significant improvement in skin hydration and a significant decrease in TEWL. No significant statistical difference was observed in minimal erythema dose (MED), overall skin elasticity (R2), or wrinkle depth, and no evidence of significant improvement in skin condition was observed. Conclusion: Meta-analysis results suggest that consume administration of fruits or fruit extracts significantly enhances skin hydration and reduces transcutaneous water loss, but there is insufficient evidence to support other outcome recommendations, including minimal erythema dose (MED), overall skin elasticity(R2), and wrinkle depth. Systematic Review Registration: PROSPERO (york.ac.uk), identifier CRD42023410382.

Stealth microplastics pollutants: Toxicological evaluation of polyethylene terephthalate-based glitters on the microalga Desmodesmus sp. and its color effect.

Polyethylene terephthalate-based glitters (PET glitters) are a potential source of primary microplastics in the environment. However, the bioeffects of PET glitters and the associated leachates remain largely unknown. In this study, we investigated the individual and combined toxicity of five colors (silver, black, red, green, and blue) of PET glitters and their corresponding leachates on the cellular responses of Desmodesmus sp. The results indicated that the photosynthesis of Desmodesmus sp. could be partly affected by PET glitters through the shading effect, but not that of growth. Conversely, the leachates of red and green PET glitters significantly inhibited the growth of the microalga, suggesting a higher risk associated with additives leached from these colors of PET glitters. Furthermore, the adverse effects of the co-occurrence of PET glitters and leachates were closely related to oxidative stress responses in the microalgal cells, along with a color effect, which could be mainly attributed to variations in the composition and abundance of toxic additives in different colors of PET glitters. Overall, our findings provide insights into the ecological risks posed by glitters in aquatic environments and emphasize the importance of considering color factors in assessing microplastics toxicity.

Role of Nano-Fe3O4 for enhancing nitrate removal in microbial electrolytic cells: Characterizations and microbial patterns of cathodic biofilm.

Conductive magnetite nanoparticle (Nano-Fe3O4) can facilitate numerous biological reduction reactions as an outstanding electron mediator for electron transfer. The positive role of Nano-Fe3O4 for nitrate removal has gradually gained attention recent years, however, it has not been clarified for the persistence of the promoting effect under different concentrations addition. Performance of nitrogen removal and characteristics of cathodic biofilm were evaluated in this study after Nano-Fe3O4 addition with gradient concentration of 100∼500 mg L-1 in microbial electrolytic cells (MEC). Our study illustrated that the optimal concentration was 200 mg L-1 as the removal rate of nitrate increased by 24.76% and the removal rate of total dissolved nitrogen by 29.72%. At the optimal concentration, Nano-Fe3O4 increased cathodic biofilm DNA concentration by 61.04%, enhanced electron transport system activity, enriched iron redox bacteria, denitrifying bacteria and genes, as well as increased extracellular polymeric substances (EPS) amount, especially the protein content of soluble-EPS. However, promoting effect on nitrate removal was not visible in high concentration (500 mg L-1) addition, its electron transport system activity and EPS content were even declined. XPS results indicated that high concentration of Nano-Fe3O4 may reduce the availability of electrons to cathodic biofilm by competing for electrons, which inhibit nitrate removal.

Transcriptome Analysis Unveiled the Intricate Interplay between Sugar Metabolism and Lipid Biosynthesis in Symplocos paniculate Fruit.

Symplocos paniculate is an oil plant exhibiting tissue-specific variations in oil content and fatty acid composition across the whole fruit (mainly pulp and seed). And its oil synthesis is intricately linked to the accumulation and transformation of sugars. Nevertheless, there remains a dearth of understanding regarding how sugar metabolism impacts oil synthesis in S. paniculate fruit. To unravel the intricate mechanism underlying the impact of sugar metabolism on lipid biosynthesis in S. paniculata fruit, a comparative analysis was conducted on the transcriptome and metabolite content of pulp and seed throughout fruit development. The findings revealed that the impact of sugar metabolism on oil synthesis varied across different stages of fruit development. Notably, during the early fruit developmental stage (from 90 to 120 DAF), pivotal genes involved in sugar metabolism, such as PGK3, PKP1, PDH-E1, MDH, and malQ, along with key genes associated with oil synthesis like KAR, HAD, and PAP were predominantly expressed in the pulp. Consequently, this preferential expression led to earlier accumulation of oil in the pulp tissue compared to the seed. Whereas, during the fruit maturity stage (from 120 DAF to 140 DAF), these genes exhibited a high level of expression in seed, thereby facilitating the rapid and substantial accumulation of seed oil compared to pulp. The sugar metabolism activity in various parts of S. paniculata fruit plays a pivotal role in oil synthesis and is contingent upon the developmental stage. These findings can offer alternative genes for further gene enhancement through molecular biotechnology, thereby augmenting fruit oil yield and altering fatty acid composition.

Network pharmacology analysis of Yi-Shen-Gu-Ta i-Ke-Li for recurrent spontaneous abortion in female fitness and athletic populations

Background: Yi-Shen-Gu-Tai-Ke-Li (YSGTKL), a renowned traditional herbal formula, has demonstrated clinical efficacy in addressing recurrent spontaneous abortion (RSA). Despite its widespread utilization in China, the current body of evidence regarding the effectiveness of its herbal components remains insufficient, and the underlying mechanisms of action remain enigmatic. This study endeavors to unravel the mechanisms responsible for the therapeutic effectiveness of YSGTKL in treating RSA, particularly within the context of female fitness and athletic populations. Methods: YSGTKL comprises various herbal plants, selected based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Specific drug targets associated with RSA were meticulously identified and corroborated using multiple reputable sources, including DrugBank, GeneCards, and Online Mendelian Inheritance in Man. The GEO database was leveraged to pinpoint differentially expressed genes (DEGs) relevant to RSA within female fitness and athletic populations. Subsequently, a comprehensive drug-compound-gene-disease network was meticulously constructed and visualized using Cytoscape software. Functional insights were gleaned through Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Within this network, a subset of hub genes was discerned through a protein-protein interaction (PPI) network analysis, specifically tailored to female fitness and athletic populations. To validate key active ingredients and core targets, molecular docking analyses were meticulously performed, taking into account the unique physiological aspects of female athletes and fitness enthusiasts. (AU).

CXCL10 and CCL5 as feasible biomarkers for immunotherapy of homologous recombination deficient ovarian cancer.

This study aims to identify biomarkers of ovarian cancer, specifically those tumors exhibiting homologous recombination deficiency (HRD), to contribute to the optimization of immunotherapy. We screened the differentially expressed genes coding for CXCL10 and CCL5 by analyzing the transcriptome data of patient with different HRD scores in the ovarian cancer cohort of the TCGA database and validated our results using pathological tissue sections. The cellular origin of CXCL10 and CCL5 were identified using the single-cell sequencing data extracted from the GEO database combined with the tumor mutational burden (TMB) and single nucleotide polymorphism (SNP) data obtained from the TCGA database. We found that CXCL10 and CCL5 expression levels were correlated with HRD score. Analysis of single-cell sequencing results and tumor mutation data suggested that both CXCL10 and CCL5 present in the tumor microenvironment were primarily derived from immune cells. In addition, we found that samples with high expression of CXCL10 and CCL5 also had higher stromal cell and immune cell scores, indicating low tumor homogeny. Further analysis showed that CXCL10 and CCL5 expression was associated with immune checkpoint-related genes, and the efficacy of using these proteins as biomarkers was significantly higher than that of PD-1 in predicting the effect of anti-PD-1 immunotherapy. The expression of CXCL10 and CCL5 had statistically different effects on the survival of patients, based on multivariate Cox regression. In summary, the results demonstrate that in ovarian cancer, the expression of CXCL10 and CCL5 are correlated with HRD. When CXCL10 and CCL5 are secreted by immune cells, immune cell infiltration can be chemotactic and predict the effect of immunotherapy more efficiently than using PD-1 as a biomarker. Therefore, CXCL10 and CCL5 look to be promising novel biomarkers to guide immunotherapy in ovarian cancer.

Elucidation of Geniposide and Crocin Accumulation and Their Biosysnthsis-Related Key Enzymes during Gardenia jasminoides Fruit Growth.

Gardenia jasminoides fruits are extensively grown worldwide, with a large harvest, and its major medicinal ingredients are geniposide and crocins. Research on their accumulation and biosynthsis-related enzymes is rare. In this study, the accumulation of geniposide and crocin of G. jasminoides fruits at different developmental stages were clarified by HPLC. The highest cumulative amount of geniposide was 2.035% during the unripe-fruit period, and the highest content of crocin was 1.098% during the mature-fruit period. Furthermore, transcriptome sequencing was performed. A total of 50 unigenes encoding 4 key enzymes related in geniposide biosynthsis pathways were screened, and 41 unigenes encoding 7 key enzymes in the pathways of crocin were elucidated. It was found that the expression levels of differentially expressed genes of DN67890_c0_g1_i2-encoding GGPS, which is highly related to geniposide biosynthesis, and DN81253_c0_g1_i1-encoding lcyB, DN79477_c0_g1_i2-encoding lcyE, and DN84975_c1_g7_i11-encoding CCD, which are highly related to crocin biosynthesis, were consistent with the accumulation of geniposide and crocin content, respectively. The qRT-PCR results showed that the trends of relative expression were consistent with transcribed genes. This study provides insights for understanding the geniposide and crocin accumulation and biosynthsis during fruit development in G. jasminoides.

Cu-Based Catalysts Supported on H3PO4-Activated Coffee Biochar for Selective Reduction of Nitroaromatics.

Selective reduction of nitroaromatics to the corresponding aromatic amines is extremely an attractive chemical process for both fundamental research and potential commercial applications. Herewith, we report that a highly dispersed Cu catalyst supported on H3PO4-activated coffee biochar and the resulting Cu/PBCR-600 catalyst show complete conversion of the nitroaromatics and >97.0% selectivity for the corresponding aromatic amines. The TOF of catalyzing the reduction of nitroaromatics (1.55-460.74 min-1) is approximately 2 to 15 times higher than those of previously reported non-noble and even noble metal catalysts. Additionally, Cu/PBCR-600 also shows high stability in catalytic recycles. Furthermore, it exhibits long-term catalytic stability (660 min) for practical application in a continuous-flow reactor. The characterizations and activity tests reveal that Cu0 existing in Cu/PBCR-600 acts as an active site in nitroaromatics reduction. Also, the further characterization by FTIR and UV-vis demonstrates that N, P co-doped coffee biochar could selectively adsorb and activate the nitro group of nitroaromatics.