[Progress in antitumor activity of diterpenoid alkaloids in plants of Aconitum].

Small-molecule compounds with rich sources have diverse structures and activities. The active ingredients in traditional Chinese medicine(TCM) provide new sources for the discovery of new antitumor drugs. Aconitum plants as Chinese medicinal plants have the effects of dispelling wind, removing dampness, warming meridian, and relieving pain. They are mainly used to treat inflammation, pain, rheumatism, and tumors, improve heart function, and dilate blood vessels in clinical practice. Diterpenoid alkaloids are the main active components of Aconitum plants, including C20-, C19-, C18-diterpenoid alkaloids and bis-diterpenoid alkaloids. Stu-dies have demonstrated that diterpenoid alkaloids can effectively treat lung cancer, liver cancer, breast cancer, colon cancer and other cancers. Diterpenoid alkaloids are considered as the most promising natural compounds against cancers. In this review, we summarized the chemical structures and antitumor activities of C20-, C19-, C18-diterpenoid alkaloids and bis-diterpenoid alkaloids extracted from plants of Aconitum, aiming to provide reference for further development of diterpenoid alkaloids from Aconitum as antitumor drugs.

NtMYB12a acts downstream of sucrose to inhibit fatty acid accumulation by targeting lipoxygenase and SFAR genes in tobacco.

MYB12 promotes flavonol biosynthesis in plants by targeting several early biosynthesis genes (EBGs) of this pathway. The transcriptions of these EBGs are also induced by sucrose signal. However, whether MYB12 is activated by sucrose signal and what the other roles MYB12 has in regulating plant metabolism are poorly understood. In this study, two NtMYB12 genes were cloned from Nicotiana tabacum. Both NtMYB12a and NtMYB12b are involved in regulating flavonoids biosynthesis in tobacco. NtMYB12a is further shown to inhibit the accumulation of fatty acid (FA) in tobacco leaves and seeds. Post-translational activation and chromatin immunoprecipitation assays demonstrate that NtMYB12a directly promotes the transcriptions of NtLOX6, NtLOX5, NtSFAR4 and NtGDSL2, which encode lipoxygenase (LOX) or SFAR enzymes catalyzing the degradation of FA. NtLOX6 and NtLOX5 are shown to prevent the accumulation of FA in the mature seeds and significantly reduced the percentage of polyunsaturated fatty acids (PUFAs) in tobacco. Sucrose stimulates the transcription of NtMYB12a, and loss function of NtMYB12a partially suppresses the decrease of FA content in tobacco seedlings caused by sucrose treatment. The regulation of sucrose on the expression of NtLOX6 and NtGDSL2 genes is mediated by NtMYB12a, whereas those of NtLOX5 and NtSFAR4 genes are independent of sucrose.

Y-chromosome evidence confirmed the Kerei-Abakh origin of Aksay Kazakhs.

Aksay Kazakhs are the easternmost branch of Kazakhs, residing in Jiuquan city, the forefront of the ancient Silk Road. However, the genetic diversity of Aksay Kazakhs and its relationships with other Kazakhs still lack attention. To clarify this issue, we analyzed the non-recombining portion of the Y-chromosome from 93 Aksay Kazakhs samples, using a high-resolution analysis of 106 biallelic markers and 17 STRs. The lowest haplogroup diversity (0.38) was observed in Aksay Kazakhs among all studied Kazakh populations. The social and cultural traditions of the Kazakhs shaped their current pattern of genetic variation. Aksay Kazakhs tended to migrate with clans and had limited paternal admixture with neighboring populations. Aksay Kazakhs had the highest frequency (80%) of haplogroup C2b1a3a1-F3796 (previous C3*-Star Cluster) among the investigated Eurasian steppe populations, which was now seen as the genetic marker of Kerei clan. Furthermore, NETWORK analysis indicated that Aksay Kazakhs originated from sub-clan Kerei-Abakh in Kazakhstan with DYS448 = 23. TMRCA estimates of three recent descent clusters detected in C2*-M217 (xM48) network, one of which incorporate nearly all of the C2b1a3a1-F3796 Aksay Kazakhs samples, gave the age range of 976-1405 YA for DC1, 1059-1314 YA for DC2, and 1139-1317 YA for DC3, respectively; this is coherent with the 7th to the 11th centuries Altaic-speaking pastoral nomadic population expansion.

A genetic variant in a homocysteine metabolic gene that increases the risk of congenital cardiac septal defects in Han Chinese populations.

Elevated homocysteine levels are known to be a risk factor for congenital cardiac septal defects (CCSDs), but the mechanism underlying this effect is unknown. The genetic variants that were significantly associated with circulating homocysteine concentrations have been systematically identified through the genome-wide association studies of one-carbon core metabolites. To examine the role of the genome-wide significant homocysteine related variants in the occurrence of CCSDs, we investigated the association between these variants and CCSDs in Han Chinese populations. Five variants of the genome-wide significant homocysteine-related genes were selected for analysis in two stages of case-controlled studies with a total of 904 CCSD patients and 997 controls. SYT9 expression was detected in human cardiovascular tissue using qRT-PCR. The intronic variant rs11041321 of the SYT9 gene was associated with an increased risk of developing CCSDs in both the separate and combined case-controlled studies. Combined samples from the two stage cohorts had a significant elevation in CCSD risk for the T allele (OR = 1.43, P = 2.6 × 10-6 ), CT genotype and TT genotype (CT: OR = 1.30, TT: OR = 2.21; P = 1 × 10-4 ) compared with the wild-type C allele and CC genotype, respectively. The risky T allele carriers exhibited decreased SYT9 mRNA expression, compared with wild-type C allele carriers. The intronic SYT9 variant rs11041321, which exhibits a significant genome-wide association with circulating homocysteine, was associated with the occurrence of CCSDs. This finding helps to characterize the unexpected role of SYT9 in homocysteine metabolism and the development of CCSDs, which further highlighted the interplay of diet, genetics, and human birth defects. © 2017 IUBMB Life, 69(9):700-705, 2017.

Effect of statins on blood pressure: Analysis on adverse events released by FDA.

OBJECTIVE: As a class of cholesterol-lowering drugs, statins have been reported to cause unexpected decrease in blood pressure (BP). However, most studies in this issue were subject to inadequate study design or very small sample size. The present study was designed to examine the BP-lowering effect of various statins. METHODS: Here we retrieved 5.9 million clinical reports submitted to FDA Adverse Event Reporting System (FAERS) from 2004 to 2015. Meta-analysis was performed to estimate the overall reporting odds ratio (ROR) of hypotension adverse events concurrent with various statins (i.e., atorvastatin, simvastatin, and rosuvastatin). RESULTS: Comparing the reporting rate of hypotension event between statins and other drugs found that atorvastatin (pooled ROR = 1.26, adjusted p-value = 8.60 × 10-4) and simvastatin (pooled ROR = 1.94, adjusted p-value = 4.16 × 10-45) were significantly associated with reduction in BP. On the other hand, the association between rosuvastatin and hypotension was observed to be nonsignificant (adjusted p-value = 0.65). CONCLUSION: To our knowledge, this is the first pooled analysis on large-scale data of adverse events to identify the BP-lowering effect of statins. The results will contribute to the development of novel statin-based antihypertensive therapies. In addition, the differential effects of individual statins can warrant subsequent research on the underlying mechanisms of BP control.

[Endovascular Treatment of Blood Blister-like Aneurysms in Internal Carotid Artery].

OBJECTIVES: To study the feasibility and effectiveness of endovascular treatment to blood blister-like aneurysms (BBA) in internal carotid artery. METHODS: Retrospective analyzed the clinical features, outcomes, and complications of 20 cases of BBA treated with endovascular intervention techniques from 2013-2015 in our center. RESULTS: The patients were treated with covered stent, internal carotid artery balloon occlusion, and stents assisted coiling, respectively. One death occurred after the patient accepted covered stent treatment, another 2 death was due to vasospasm after internal carotid artery balloon occlusion, and double stents assisted coiling, respectively. The modified Rankin Scale (mRS) score when patients being discharged were 0-2 in 15 cases, and 3-4 in 2 cases. There were 17 cases with clinical follow-up from 1 to 26 months (9.3 months on average), the mRS scores were all less than 2 points. 16 cases accepted angiographic review. 14 cases had BBA totally occluded, 1 case had stable neck residue, and 1 case had incompleted occlusion and the aneurysm dwindled at follow-up. CONCLUSIONS: Stent-assisted coiling is feasible and effective in the treatment of BBA in internal carotid artery.

Prognosis research of delayed facial palsy after microvascular decompression for hemifacial spasm.

BACKGROUND: Although microvascular decompression (MVD) surgery has been widely accepted as an effective treatment for hemifacial spasm (HFS), delayed facial palsy (DFP) is not an unusual complication, but it has only been sporadically described in the literature. The purpose of this study was to examine the probability of occurrence, the risk/predisposing factors, and the prognosis and timing of DFP. METHODS: A prospective cohort study was conducted that included patients diagnosed with HFS and treated by MVD at our institution. All patients were followed up at the outpatient department or by telephone from December 2009 to December 2014. Categorical variables were analyzed using the Pearson's Chi-square test or Fisher's exact test. Continuous variables were compared using the independent Student's t test. The Spearman rank test was used to determine the correlation between the time of onset and the duration of DFP. The risk/predisposing factors were analyzed by the logistic regression method. RESULTS: We enrolled 248 patients who were treated by MVD for HFS. During the follow-up period, 16 patients (6.5 %) developed DFP. Fifteen of those patients had a complete recovery, and in one patient the facial palsy did not resolve. The average onset time was 10.2 days (range, 2-30 days) after surgery, and the mean duration of DFP after MVD, with exclusion of the permanent facial palsy patient, was 59.7 days (range, 7-220 days). The time of onset was correlated with the duration of DFP after MVD (p = 0.036). Furthermore, hypertension contributed to DFP (odds ratio [OR] 4.226, 95 % confidence interval [CI] 1.089-16.401, p = 0.037). CONCLUSIONS: Although the degree of facial palsy was variable, most patients experienced a complete recovery without requiring any special treatment. DFP may be a self-healing disease that resolves spontaneously without any treatment. The time of onset was correlated with the duration of DFP; i.e., an earlier development of DFP corresponded with a shorter duration, whereas a later development of DFP corresponded with a longer duration. Our results also suggest that hypertension contributes to DFP.

Magnetic resonance imaging-based lymph node radiomics for predicting the metastasis of evaluable lymph nodes in rectal cancer.

BACKGROUND: Lymph node (LN) staging in rectal cancer (RC) affects treatment decisions and patient prognosis. For radiologists, the traditional preoperative assessment of LN metastasis (LNM) using magnetic resonance imaging (MRI) poses a challenge. AIM: To explore the value of a nomogram model that combines Conventional MRI and radiomics features from the LNs of RC in assessing the preoperative metastasis of evaluable LNs. METHODS: In this retrospective study, 270 LNs (158 nonmetastatic, 112 metastatic) were randomly split into training (n = 189) and validation sets (n = 81). LNs were classified based on pathology-MRI matching. Conventional MRI features [size, shape, margin, T2-weighted imaging (T2WI) appearance, and CE-T1-weighted imaging (T1WI) enhancement] were evaluated. Three radiomics models used 3D features from T1WI and T2WI images. Additionally, a nomogram model combining conventional MRI and radiomics features was developed. The model used univariate analysis and multivariable logistic regression. Evaluation employed the receiver operating characteristic curve, with DeLong test for comparing diagnostic performance. Nomogram performance was assessed using calibration and decision curve analysis. RESULTS: The nomogram model outperformed conventional MRI and single radiomics models in evaluating LNM. In the training set, the nomogram model achieved an area under the curve (AUC) of 0.92, which was significantly higher than the AUCs of 0.82 (P < 0.001) and 0.89 (P < 0.001) of the conventional MRI and radiomics models, respectively. In the validation set, the nomogram model achieved an AUC of 0.91, significantly surpassing 0.80 (P < 0.001) and 0.86 (P < 0.001), respectively. CONCLUSION: The nomogram model showed the best performance in predicting metastasis of evaluable LNs.

Sophora subprostrate polysaccharide targets LncRNA MSTRG.5823.1 to suppress PCV2-mediated immunosuppression via TNF/NF-κB signaling.

Current evidence suggests that porcine circovirus type 2 (PCV2) infection induces immunosuppression in piglets. Sophora subprostrate polysaccharide (SSP) exhibits various pharmacological activities, including immunoregulatory, anti-inflammatory, antiviral, and antioxidant properties. However, the acts of lncRNAs in regulating the therapeutic effects of SSP on PCV2-infected RAW264.7 cells remains poorly understood. This study aimed to investigate the molecular mechanisms by which lncRNAs regulate PCV2-induced immunosuppression during SSP treatment. Our findings revealed that 1699 mRNAs, 373 lncRNAs, and 129 miRNAs were differentially expressed in PCV2-infected RAW264.7 cells. Additionally, 359 mRNAs, 271 lncRNAs, and 79 miRNAs exhibited differential expression in SSP-treated PCV2-infected RAW264.7 cells. GO and KEGG analyses indicated that the candidate genes were enriched in the TNF/NF-κB signaling pathway. Furthermore, based on GO and KEGG pathway analysis, a ceRNA network involving chemokine (C-X-C motif) ligand 2 (CXCL2), miR-217-x, and MSTRG.5823.1 was constructed. We demonstrated that lncRNA MSTRG.5823.1 localized to the cytoplasm. Moreover, we found that silencing or overexpressing lncRNA MSTRG.5823.1 significantly modulated PCV2-induced immunosuppression by regulating the activation of the TNF/NF-κB signaling pathway. Specifically, lncRNA MSTRG.5823.1 overexpression increased the expression of TNF/NF-κB signaling pathway-related genes and proteins in PCV2-infected RAW264.7 cells. Conversely, silencing lncRNA MSTRG.5823.1 decreased their expression. Rescue assays further revealed that the suppressive effects of miR-217-x overexpression on TNF/NF-κB signaling pathway-related genes and proteins could be reversed by MSTRG.5823.1 overexpression. These findings highlight the critical role of lncRNA MSTRG.5823.1 in PCV2 infection progression and suggest a new strategy for the prevention and treatment of PCV2 infection.

Polysaccharide of Asparagus cochinchinensis (Lour.) Merr regulates macrophage immune response and epigenetic memory through TLR4-JNK/p38/ERK signaling pathway and histone modification.

BACKGROUND: Innate immune memory of macrophages is closely linked to histone modifications. While various studies have demonstrated that the polysaccharide of Asparagus cochinchinensis (Lour.) Merr (ACMP), extracted through alcohol-alkali extraction, enhances macrophages' non-specific immune function; no literature currently addresses whether ACMP's regulatory effect is related to innate immune memory and histone modification. PURPOSE: This study aims to investigate if ACMP induces innate immune memory emergence in macrophages via pattern recognition receptor (PRR). STUDY DESIGN: After co-incubating different doses of ACMP with RAW264.7 cells and BMDM cells, we observed changes in signaling pathways related to PRR and assessed the presence of innate immune memory phenomenon in the cells. METHODS: We observed the morphological characteristics of the ACMP using a scanning electron microscope, infrared spectrum, and HPLC pre-column derivatization method. We used q-PCR, Western blot, RNA-seq, and CUT&Tag-seq methods to examine ACMP's regulation of macrophage immune response and innate immune memory and explored its specific mechanism. RESULTS: ACMP, primarily composed of Man, GlcN, Rha, Fuc, GalA, Xyl, Glc, Gal, Ara, and, exhibited a molar ratio of each monosaccharide (1.41: 0.35: 0.49: 0.18: 1.00: 97.12: 0.36: 3.58: 1.14). ACMP regulated immunological function in macrophages through the TLR4-MAPK-JNK/p38/ERK pathway. ACMP induced elevated levels of chromosomal H3K4me1, enhancing TNF-α, IL-1ß, and other genes' responsiveness, allowing macrophages to develop innate immune memory to ACMP stimulation. CONCLUSION: This study first time demonstrates that ACMP regulates immunological function through the TLR4-MAPK-JNK/ERK/p38 signaling pathway, distinct from prior reports. ACMP induces innate immune memory in macrophages in response to its immune stimulation by promoting increased H3K4me1 on chromosomes. This mechanism may be crucial in how plant polysaccharides regulate macrophages and the body's immune function.

Two new neuroprotective phenolic compounds from Gastrodia elata.

Two new phenolic compounds 4-(4'-hydroxybenzyl) phenyl glucoside (gastrodin B, 1) and 1'-hydroxymethyl-phenyl 4-hydroxy-3-(4″-hydroxybenzyl) benzyl ether (gastrol B, 2) were isolated from the rhizomes of Gastrodia elata. Their structures were elucidated on the basis of spectroscopic data and chemical reaction. All compounds exhibited potent neuroprotective activity against H2O2-induced PC12 cell damage.

[Preventive effect of low-dose carvedilol combined with candesartan on the cardiotoxicity of anthracycline drugs in the adjuvant chemotherapy of breast cancer].

OBJECTIVE: To investigate the effect of low-dose carvedilol combined with candesartan in the prevention of acute and chronic cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer. METHODS: Forty patients were randomly divided into two groups: the experimental group with chemotherapy plus low-dose carvedilol combined with candesartan (20 cases) and control group with chemotherapy alone (20 cases). The same chemotherapy was given to the two groups. All the 40 patients had no contraindication for carvedilol and candesartan. Patients of the experimental group received low-dose carvedilol from 2.5 mg orally twice a day at first cycle to 5 mg twice a day gradually if no side reactions, and candesartan 2.5 mg orally once a day. Electrocardiogram, ultrasonic cardiogram, arrhythmia, troponin and non-hematologic toxicity were recorded and compared after the second, forth and sixth cycle of chemotherapy. Each cycle included 21 days. RESULTS: LVEF was decreased along with the prolongation of chemotherapy in the experimental group and control group. LVEDD and LVESD showed no significant changes in the experimental group, but gradually increased in the control group. After four and six cycles of chemotherapy, LVEF were (57.00 ± 5.13)% and (45.95 ± 3.68)%, respectively, in the control group, significantly lower than that of (67.00 ± 5.13)% and (57.50 ± 2.57)%, respectively, in the experimental group (P < 0.05). After six cycles of chemotherapy, LVEDD and LVESD were (50.00 ± 10.48) mm and (35.01 ± 2.99) mm, respectively, in the control group, significantly higher than those before chemotherapy (P < 0.05) and experimental group (P < 0.001). The rate of ST segment and T wave abnormalities was 80.0% in the control group after six cycles of chemotherapy, significantly higher than that of 25.0% after four cycles of chemotherapy (P = 0.001) and 10.0% after two cycles of chemotherapy (P < 0.001). The reduction of QRS voltage, arrhythmia and abnormal troponin were 55.0%, 45.0% and 45.0%, respectively, in the control group, significantly higher than those in the experimental group (20.0%, P < 0.05), (10.0%, P = 0.010) and (10.0%, P < 0.05), respectively. The rate of abnormal expression of troponin was 45.0% in the control group, significantly higher than the 10.0% in the experimental group (P < 0.05). CONCLUSIONS: The use of low-dose carvedilol combined with candesartan can reduce the acute and chronic cardiotoxicity of anthracycline drugs, and with tolerable toxicities. This may provide a new approach to prevent cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer.

[Autologous cytokine-induced killer cells therapy on the quality of life of patients with breast cancer after adjuvant chemotherapy: a prospective study].

OBJECTIVE: To explore the effect of autologous cytokine-induced killer cells on the quality of life in patient with breast cancer who have already finished the adjuvant chemotherapy. METHODS: One hundred and twenty-eight postoperative patients with breast cancer who underwent anthracycline-based adjuvant chemotherapy were enrolled in this prospective study, and they were randomized into 2 groups, i.e., treatment group, which received the therapy of CIK cells transfusion, and control group, which was given regular follow-up. Meanwhile, patients with positive hormone receptor in the two groups were given endocrine therapy, and the patients with positive axillary lymph nodes were given radiotherapy to the chest wall and regional lymph nodes. The difference of quality of life between the two groups was analyzed according to the EORTC QLQ-BR53 quality of life questionnaire, and the adverse reactions were monitored. RESULTS: As regarding the functional evaluation, the physical function scores of patients of the treatment group were (83.43 ± 14.87) and (88.55 ± 11.62) at 3 and 6 months after the CIK cell therapy, respectively, significantly higher than the baseline value [(74.83 ± 13.82), P < 0.05)]. Global health status/QOL scores were (83.30 ± 19.09) and (89.68 ± 10.81), significantly higher than the baseline value [(77.72 ± 21.05), P < 0.05]. As regarding symptoms, the scores of fatigue, nausea, vomiting and loss of appetite of patients in the treatment group were higher than the baseline value, with significant differences (P < 0.05). The nausea and vomiting scores in the control group at 3 and 6 months of followed-up were (26.67 ± 22.56) and (21.47 ± 21.06), significantly lower than the baseline values [(33.31 ± 27.07), P < 0.05]. The scores of worrying about the future in the patients of treatment group were (47.56 ± 30.84) and (42.33 ± 26.95) after 3 and 6 months, significantly better than the baseline value [(57.41 ± 30.63), P < 0.05]. The systematic therapy side effects scores were (31.95 ± 27.52) and (23.72 ± 22.87), significantly better than the baseline value [(40.56 ± 26.28), P < 0.05]. The scores of arm edema were (45.26 ± 25.42) and (36.61 ± 20.51), significantly milder than the baseline value [(55.11 ± 22.82), P < 0.05]. In the control group, the scores of arm edema were (44.85 ± 28.94) and (38.64 ± 23.68), significantly lower than the baseline values [(53.26 ± 23.84) points, P < 0.05]. Alopecia scores were (29.93 ± 24.72) and (24.18 ± 22.66), significantly lower than the baseline values [(35.92 ± 22.08), P < 0.05]. In the treatment group, the patients' physical function, social function and global health status/QOL, fatigue, insomnia, and worrying about the future rates were significantly higher than that of the control group (P < 0.05 for all). Three patients after CIK reinfusion had transient fever, and 6 cases felt pain in the lower limb, but the symptoms were relieved after symptomatic treatment. CONCLUSIONS: Therapy of autologous CIK cells transfusion can significantly improve the quality of life of breast cancer patients, and the adverse reactions during the treatment can be alleviated by symptomatic treatment.

[A new method to determine the proportion of characters F2 in the Mendelian inheritance-the observation method of dominant traits].

A new method, the observation method of dominant traits, which can be used for determining the proportion of characters from F2 under the Mendelian Inheritance, was discovered. The principle of this method is that people can conclude a general formula:3n1 (n1: the number of dominant characters types in F2) based on the proportion of characters from F2 under the Mendelian Inheritance. This method is more convenient and time-saving than common tests in teaching and practice of classic genetics.

[Contact and admixture-the relationship between Dongxiang population and their language viewed from Y chromosomes].

Dongxiang is one of special ethnic groups of Gansu Province. Their language is one of the Mongolian languages of Altai language family. And their origin has long been controversial. The results of Cluster analyses (multidimensional scaling analysis, dendrograms, principal component analyses, and networks) of Dongxiang population and other ethnic groups indicated that Dongxiang people is much closer to the Central Asian ethnic groups than to the other Mongolian. Admixture analyses also confirmed the result. This suggests that Dongxiang people did not descend from Mongolian, but from the Central Asian ethnic groups that have spoken Persian or Turkic language. This mismatch between paternal genetic lineage and language classification might be explained by the elite-dominance model. The ancestral populations of Dongxiang could be the Central Asian ethnic groups assimilated by Mongolian in language and culture.

[Impact of Climate Change on Summer Ozone in China].

Meteorological conditions have important impacts on surface ozone (O3) formation. To evaluate the influence of future climate change on O3 concentrations in different regions of China, this study employed the climate data from the community earth system model provided by the CMIP5 under the RCP4.5, RCP6.0, and RCP8.5 scenarios to generate the initial and boundary conditions for the WRF model. Then, the dynamic downscaling WRF results were fed into a CMAQ model as meteorological fields with fixed emission data. Two 10-year periods (2006-2015 and 2046-2055) were selected in this study to discuss the impacts of climate change on O3. The results showed that climate change increased boundary layer height, mean temperature, and heatwave days in China during summer. Relative humidity decreased and wind speed near the surface showed no obvious change in the future. O3 concentration showed an increasing trend in Beijing-Tianjin-Hebei, Sichuan Basin, and South China. The extreme value of O3 maximum daily 8-hour moving average (MDA8) showed an increasing trend, following the order of RCP8.5 (0.7 µg·m-3)>RCP6.0 (0.3 µg·m-3)>RCP4.5 (0.2 µg·m-3). The number of days exceeding the standard for summer O3 had a similar spatial distribution with the heatwave days in China. The increase in heatwave days led to the increase in O3 extreme pollution events, and the possibility of a long-lasting O3 pollution event will increase in China in the future.

Effects of different water quality regulators on growth performance, immunologic function, and domestic water quality of GIFT tilapia.

Water quality regulation is widely recognized as a highly effective strategy for disease prevention in the field of aquaculture, and it holds significant potential for the development of sustainable aquaculture. Herein, four water quality regulators, including potassium monopersulfate (KMPS), tetrakis hydroxymethyl phosphonium sulfate (THPS), bacillus subtilis (BS), and chitosan (CS), were added to the culture water of Oreochromis niloticus (GIFT tilapia) every seven days. Subsequently, the effects of these four water quality regulators on GIFT tilapia were comprehensively evaluated by measuring the water quality index of daily growth-related performance and immune indexes of GIFT tilapia. The findings indicated that implementing the four water quality regulators resulted in a decrease in the content of ammonia nitrogen, active phosphate, nitrite, total organic carbon (TOC), and chemical oxygen demand (COD) in the water. Additionally, these regulators were found to maintain dissolved oxygen (DO) levels and pH of the water effectively. Furthermore, using these regulators demonstrated positive effects on various physiological parameters of GIFT tilapia, including improvements in final body weight, weight gain rate (WGR), specific growth rate (SGR), condition factor (CF), feed conversion ratio (FCR), spleen index (SI), hepato-somatic index (HSI), immune cell count, the activity of antioxidant-related enzymes (Nitric oxide, NO and Superoxide dismutase, SOD), and mRNA expression levels of immunity-related factors (Tumor Necrosis Factor-alpha, TNF-α and Interleukin-1 beta, IL-1ß) in the liver and spleen. Notably, the most significant improvements were observed in the groups treated with the BS and CS water quality regulators. Moreover, BS and CS groups exhibited significantly higher serum levels of albumin (ALB) and total protein (TP) (P < 0.05), whereas the other indicators showed no significant difference (P > 0.05) compared to the control group. However, the KMPS and THPS groups of GIFT tilapia exhibited significantly higher serum levels of aspartate aminotransferase (AST), alanine transaminase (ALT), creatinine (CRE) and blood urea nitrogen (BUN) (P < 0.05), whereas they exhibited significantly decreased HSI (P < 0.05). In addition, the partially pathological observations revealed the presence of cell vacuolation, nuclear shrinkage, and pyknosis within the liver. In conclusion, these four water quality regulators, mainly BS and CS, could improve the growth performance and immunity of GIFT tilapia to varying degrees by regulating the water quality and then further increasing the expression levels of immune-related factors or the activity of antioxidant-related enzymes of GIFT tilapia. On the contrary, the prolonged use of KMPS and THPS may gradually diminish their growth-enhancing properties and potentially hinder the growth of GIFT tilapia.

RNA-Seq and 16S rRNA Reveals That Tian-Dong-Tang-Gan Powder Alleviates Environmental Stress-Induced Decline in Immune and Antioxidant Function and Gut Microbiota Dysbiosis in Litopenaeus vannami.

Ammonia stress and nitrite stress can induce immune depression and oxidative stress in Litopenaeus vannami (L. vannamei). Earlier reports showed that L. vannamei immunity, resistance to ammonia stress, and resistance to nitrite stress improved after Tian-Dong-Tang-Gan Powder (TDTGP) treatment, but the mechanism is not clear. In this study, three thousand L. vannamei were fed different doses of TDTGP for 35 days and then subjected to ammonia and nitrite stress treatments for 72 h. Transcriptome and 16-Seq ribosomal RNA gene sequencing (16S rRNA-seq) were used to analyze hepatopancreas gene expression and changes in gut microbiota abundance in each group. The results showed that after TDTGP treatment, hepatopancreas mRNA expression levels of immunity- and antioxidant-related genes were increased, the abundance of Vibrionaceae in the gut microbiota was decreased, and the abundance of Rhodobacteraceae and Flavobacteriaceae was increased. In addition, after TDTGP treatment, the effects of ammonia and nitrite stress on the mRNA expression of Pu, cat-4, PPAF2, HO, Hsp90b1, etc. were reduced and the disruption of the gut microbiota was alleviated. In short, TDTGP can regulate the immunity and antioxidant of L. vannamei by increasing the expression levels of immunity- and antioxidant-related genes and regulating the abundance of Rhodobacteraceae and Flavobacteriaceae in the gut microbiota.

Association of STAT4 rs7574865 polymorphism with autoimmune diseases: a meta-analysis.

The association between the signal transducer and activator of transcription 4 (STAT4) gene rs7574865 single nucleotide polymorphism and different autoimmune diseases remains controversial and ambiguous. We conducted this study to investigate whether combined evidence shows the association between STAT4 rs7574865 polymorphism and autoimmune diseases. Comprehensive Medline search and review of the references were used to get the relevant reports published before September 2011. Meta-analysis was conducted for genotype T/T (recessive effect), T/T + G/T (dominant effect) and T allele in random effects models. 40 studies with 90 comparisons including 32 systemic lupus erythematosus (SLE), 19 rheumatoid arthritis (RA), 3 type 1 diabetes (T1D), 11 Systemeric Sclerosis (SSc), 4 inflammatory bowed diseases (IBD), 3 Primary Sjogren's syndrome (pSS), 4 juvenile idiopathic arthritis (JIA), 2 Primary antiphospholipid syndrome (APS), 1 Autoimmune thyroid diseases, 1 multiple sclerosis, 1 Psoriasis, 1 Wegener's granulomatosis, 1 Type 2 diabetes, and 1 giant cell arteritis disease were available for this meta-analysis. The overall odds ratios for rs7574865 T-allele significantly increased in SLE, RA, T1D, SSc, JIA, and APS (OR = 1.56, 1.25, 1.13, 1.34, 1.25, and 2.15, respectively, P < 0.00001) and in IBD-UC and pSS (OR = 1.11 and 1.33, respectively, P < 0.05). This meta-analysis demonstrates that the STAT4 rs7574865 T allele confers susceptibility to SLE, RA, T1D, SSc, JIA, APS, IBD-UC, and pSS patients, supporting the hypothesis of association between STAT4 gene polymorphism and subgroup of autoimmune diseases.

Mitochondrial genome evidence reveals successful Late Paleolithic settlement on the Tibetan Plateau.

Due to its numerous environmental extremes, the Tibetan Plateau--the world's highest plateau--is one of the most challenging areas of modern human settlement. Archaeological evidence dates the earliest settlement on the plateau to the Late Paleolithic, while previous genetic studies have traced the colonization event(s) to no earlier than the Neolithic. To explore whether the genetic continuity on the plateau has an exclusively Neolithic time depth, we studied mitochondrial DNA (mtDNA) genome variation within 6 regional Tibetan populations sampled from Tibet and neighboring areas. Our results confirm that the vast majority of Tibetan matrilineal components can trace their ancestry to Epipaleolithic and Neolithic immigrants from northern China during the mid-Holocene. Significantly, we also identified an infrequent novel haplogroup, M16, that branched off directly from the Eurasian M founder type. Its nearly exclusive distribution in Tibetan populations and ancient age (>21 kya) suggest that M16 may represent the genetic relics of the Late Paleolithic inhabitants on the plateau. This partial genetic continuity between the Paleolithic inhabitants and the contemporary Tibetan populations bridges the results and inferences from archaeology, history, and genetics.