Facet-dependent transformation and toxicity of nanoscale zinc oxide in the synthetic saliva.

The nanoscale zinc oxide (n-ZnO) was used in food packages due to its superior antibacterial activity, resulting in potential intake of n-ZnO through the digestive system, wherein n-ZnO interacted with saliva. In recent, facet engineering, a technique for controlling the exposed facets, was applied to n-ZnO, whereas risk of n-ZnO with specific exposed facets in saliva was ignored. ZnO nanoflakes (ZnO-0001) and nanoneedles (ZnO-1010) with the primary exposed facets of {0001} and {1010} respectively were prepared in this study, investigating stability and toxicity of ZnO-0001 and ZnO-1010 in synthetic saliva. Both ZnO-0001 and ZnO-1010 partially transformed into amorphous Zn3(PO4)2 within 1 hr in the saliva even containing orgnaic components, forming a ZnO-Zn3(PO4)2 core-shell structure. Nevertheless, ZnO-1010 relative to ZnO-0001 would likely transform into Zn3(PO4)2, being attributed to superior dissolution of {1010} facet due to its lower vacancy formation energy (1.15 eV) than {0001} facet (3.90 eV). The toxicity of n-ZnO to Caco-2 cells was also dependent on the primary exposed facet; ZnO-0001 caused cell toxicity through oxidative stress, whereas ZnO-1010 resulted in lower cells viability than ZnO-0001 through oxidative stress and membrane damage. Density functional theory calculations illustrated that ·O2- was formed and released on {1010} facet, yet O22- instead of ·O2- was generated on {0001} facet, leading to low oxidative stress from ZnO-0001. All findings demonstrated that stability and toxicity of n-ZnO were dependent on the primary exposed facet, improving our understanding of health risk of nanomaterials.

Single-cell transcriptome analysis and in vitro differentiation of testicular cells reveal novel insights into male sterility of the interspecific hybrid cattle-yak.

BACKGROUND: Interspecific hybridization plays vital roles in enriching animal diversity, while male hybrid sterility (MHS) of the offspring commonly suffered from spermatogenic arrest constitutes the postzygotic reproductive isolation. Cattle-yak, the hybrid offspring of cattle (Bos taurus) and yak (Bos grunniens) can serve as an ideal MHS animal model. Although meiotic arrest was found to contribute to MHS of cattle-yak, yet the cellular characteristics and developmental potentials of male germline cell in pubertal cattle-yak remain to be systematically investigated. RESULTS: Single-cell RNA-seq analysis of germline and niche cell types in pubertal testis of cattle-yak and yak indicated that dynamic gene expression of developmental germ cells was terminated at late primary spermatocyte (meiotic arrest) and abnormal components of niche cell in pubertal cattle-yak. Further in vitro proliferation and differentially expressed gene (DEG) analysis of specific type of cells revealed that undifferentiated spermatogonia of cattle-yak exhibited defects in viability and proliferation/differentiation potentials. CONCLUSION: Comparative scRNA-seq and in vitro proliferation analysis of testicular cells indicated that not only meiotic arrest contributed to MHS of cattle-yak. Spermatogenic arrest of cattle-yak may originate from the differentiation stage of undifferentiated spermatogonia and niche cells of cattle-yak may provide an adverse microenvironment for spermatogenesis.

Modeling the resistive viscoelasticity of conductive polymer composites for sensor usage.

With the development of fully printed electronics, soft sensors are in demand in various fields, such as wearable electronics, soft machines, etc. Most soft resistive sensors are made of conductive elements dispersed in a viscoelastic polymer binder, exhibiting resistive viscoelastic behavior. The resistance of soft resistive sensors is time-dependent due to the viscoelastic response of polymer binder and structural rearrangement of the conductive pathway. In this paper, experiments and theoretical modeling are used to study the resistive viscoelastic behavior of printed silver wires. The printed silver wire belongs to conductive polymer composites (CPCs) consisting of conductive silver-nanoparticle pathways in an elastic polymer binder. Based on tunneling theory, a multi-branch model is developed to capture the resistance variation of the printed silver wire under mechanical loading. Our experiment-validated model uses only a single set of parameters to predict the resistive relaxation behaviors of CPCs under different strain and different loading rates. Moreover, we demonstrated this numerical model could describe the resistance response under complex loading conditions, such as cyclic loading, similar to the sensor's working condition. The multi-branch model can be extended to any other soft resistive sensor, such as a strain sensor, and provide a new avenue to calibrate these soft sensors.

Prevalence and risk factors of suicide attempts in young, first-episode and drug-naïve Chinese Han outpatients with psychotic major depressive disorder.

This study investigates the relationship between psychotic symptoms and suicide attempts in young first-episode, drug-naive Chinese Han outpatients diagnosed with Major Depressive Disorder (MDD). The prevalence of Psychotic Major Depressive Disorder (PMD) was found to be 8.3% among the enrolled MDD patients. The study assessed 1289 participants using various scales to evaluate the severity of clinical symptoms, including the CGI-S, the HAMD, the HAMA, and the PANSS positive subscale. Additionally, thyroid hormone and glucolipid metabolism indicators were examined. The findings indicate that among patients with PMD, 41.12% had recent suicide attempts, while 6.54% had previous suicide attempts. Patients who recently attempted suicide exhibited higher scores on the HAMA and CGI scales, along with elevated serum levels of Thyroid-Stimulating Hormone (TSH) and total cholesterol (TC), as well as higher systolic and diastolic blood pressure. Notably, TSH levels independently correlated with recent suicide attempts in PMD patients, with an impressive area under the receiver operating characteristic curve (AUROC) of 0.923. Furthermore, the subgroup of patients with previous suicide attempts displayed longer illness duration and higher HAMD scores. Duration of illness and HAMD were found to be independently associated with previous suicide attempts among PMD patients, with a combined predictive effect showing a robust AUROC of 0.910. In conclusion, this study highlights the significant prevalence of recent and previous suicide attempts among young Chinese Han outpatients with PMD. The identification of risk factors, especially the link between TSH levels and recent suicide attempts, offers valuable insights for clinicians to develop targeted interventions and preventive strategies for this vulnerable patient population.

Epigenomics Analysis of the Suppression Role of SIRT1 via H3K9 Deacetylation in Preadipocyte Differentiation.

Sirtuin 1 (SIRT1) overexpression significantly inhibits lipid deposition during yak intramuscular preadipocyte (YIMA) differentiation; however, the regulatory mechanism remains unknown. We elucidated the role of SIRT1 in YIMA differentiation using lentivirus-mediated downregulation technology and conducted mRNA-seq and ChIP-seq assays using H3K9ac antibodies after SIRT1 overexpression in order to reveal SIRT1 targets during YIMA adipogenesis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed in order to identify the functional annotation of common genes. In addition, a potential target of SIRT1 was selected to verify its effects on the differentiation and proliferation of YIMAs. SIRT1 interfered with lipid deposition and promoted YIMA differentiation. In total, 143,518 specific peaks were identified after SIRT1 overexpression, where genes associated with downregulation peaks were enriched in transcription, gene expression, lipid-related processes, and classical lipid-related pathways. The H3K9ac signal in the whole genome promoter region (2 kb upstream and downstream of the transcription start site (TSS)) was weakened, and the peaks were distributed across all gene functional regions. Genes that lost signals in their TSS region or gene body region were enriched in both biological processes and pathways associated with lipogenesis. The ChIP-seq results revealed 714 common differential genes in mRNA-seq, which were enriched in "MAPK signaling", "lipid and atherosclerosis", "mTOR signaling", and "FoxO signaling" pathways. A total of 445 genes were downregulated in both their H3K9ac signals and mRNA expression, and one of their most significantly enriched pathways was FoxO signaling. Nine genes (FBP2, FPGT, HSD17B11, KCNJ15, MAP3K20, SLC5A3, TRIM23, ZCCHC10, and ZMYM1) lost the H3K9ac signal in their TSS regions and had low mRNA expression, and three genes (KCNJ15, TGM3, and TRIM54) had low expression but lost their H3K9ac signal in the gene body region. The interference of TRIM23 significantly inhibited fat deposition during preadipocyte differentiation and promoted cell proliferation by increasing S-phase cell numbers. The present study provides new insights into the molecular mechanism of intramuscular fat content deposition and the epigenetic role of SIRT1 in adipocyte differentiation.

Comparative transcriptome analysis of winter yaks in plateau and plain.

The yak is an important source for the people living and ecological environment in the Qinghai-Tibet Plateau. In every winter, many domestic yaks will lose bodyweight or dead under cold and food scarcity. Moving the plateau yaks to farm in the plain is a useful approach to reduce their environmental stress and gain more production. In this study, we measured growth, slaughter and beef quality traits every month and sequenced mRNA expression levels of muscles of two groups yaks living in plateau and plain respectively. We found there is significant difference (p-value <0.01) in the third (60 days), fourth (90 days), fifth (120 days) and sixth (150 days) weights between subpopulations in the plateau and plain. We identified 540 different expressed genes (DEGs) including 123 known genes and 417 unknown genes. Using the weighted correlation network analysis (WGCNA) to build a co-express network, the modules were strong relative to weight traits. The findings highlighted the underlying way and a relative network to yield a new view about gene expression between the yaks living plateau and plain.

A study of the correlation between M2 macrophages and lymph node metastasis of colorectal carcinoma.

BACKGROUND: Lymph node metastasis is a major prognostic sign of colorectal carcinoma and an important indicator for individualized treatment. M2 macrophages play a key role in carcinogenesis and tumor development by enhancing invasiveness and promoting lymph node metastasis. The purpose of this study was to investigate the effect of CD163-positive M2 macrophages on lymph node metastasis in colorectal carcinoma. METHODS: Postoperative lymph node tissues were obtained from 120 patients with colorectal carcinoma who underwent radical surgery in the First Affiliated Hospital of Jinzhou Medical University between December 2019 and May 2020. We detected the expression of the CD163 protein in lymph nodes using immunohistochemistry. Furthermore, the relationships between M2 macrophages identified by expression of CD163 and lymph node metastasis were analyzed using the independent sample t-test and Chi-square test. RESULTS: M2 macrophages were increased in metastatic lymph nodes and non-metastatic lymph nodes adjacent to the cancer. The M2 macrophage count was higher in patients with macro-metastases than in patients with micro-metastases. CONCLUSIONS: The presence of M2 macrophages represents an important indicator for lymph node metastasis in colorectal carcinoma and may be a potential marker for its prediction. Thus, M2 macrophage localization might offer a new target for the comprehensive treatment of colorectal carcinoma.

The whole-transcriptome landscape of muscle and adipose tissues reveals the ceRNA regulation network related to intramuscular fat deposition in yak.

BACKGROUND: The Intramuscular fat (IMF) content in meat products, which is positively correlated with meat quality, is an important trait considered by consumers. The regulation of IMF deposition is species specific. However, the IMF-deposition-related mRNA and non-coding RNA and their regulatory network in yak (Bos grunniens) remain unknown. High-throughput sequencing technology provides a powerful approach for analyzing the association between transcriptome-related differences and specific traits in animals. Thus, the whole transcriptomes of yak muscle and adipose tissues were screened and analyzed to elucidate the IMF deposition-related genes. The muscle tissues were used for IMF content measurements. RESULTS: Significant differences were observed between the 0.5- and 2.5-year-old yaks. Several mRNAs, miRNAs, lncRNAs and circRNAs were generally expressed in both muscle and adipose tissues. Between the 0.5- and 2.5-year-old yaks, 149 mRNAs, 62 miRNAs, 4 lncRNAs, and 223 circRNAs were differentially expressed in muscle tissue, and 72 mRNAs, 15 miRNAs, 9 lncRNAs, and 211 circRNAs were differentially expressed in adipose tissue. KEGG annotation revelved that these differentially expressed genes were related to pathways that maintain normal biological functions of muscle and adipose tissues. Moreover, 16 mRNAs, 5 miRNAs, 3 lncRNAs, and 5 circRNAs were co-differentially expressed in both types of tissue. We suspected that these co-differentially expressed genes were involved in IMF-deposition in the yak. Additionally, LPL, ACADL, SCD, and FASN, which were previously shown to be associated with the IMF content, were identified in the competing endogenous RNA (ceRNA) regulatory network that was constructed on the basis of the IMF deposition-related genes. Three ceRNA subnetworks also revealed that TCONS-00016416 and its target SIRT1 "talk" to each other through the same miR-381-y and miR-208 response elements, whereas TCONS-00061798 and its target PRKCA, and TCONS-00084092 and its target LPL "talk" to each other through miR-122-x and miR-499-y response elements, respectively. CONCLUSION: Taken together, our results reveal the potential mRNA and noncoding RNAs involved in IMF deposition in the yak, providing a useful resource for further research on IMF deposition in this animal species.

Detection and integrated analysis of lncRNA and mRNA relevant to plateau adaptation of Yak.

Known as the 'ship of the plateau', through thousands of years evolution and cruelty environments selection containing low oxygen and strong ultraviolet radiation, yaks have adapted plateau environments and supplied important goods and materials for the people in the Qinghai-Tibet Plateau. This study aimed to identify differentially expressed (DE) genes and novel long non-coding RNAs (lncRNAs) of yaks for the Plateau adaptation and their underlying co-expression and regulatory network. We carried out RNA-seq analysis for cerebral and cerebellar tissue specimens of Bos taurus, Bos grunniens × Bos Taurus and B. grunniens. Furthermore, 12,072 pseudo lncRNAs were predicted using three software. In total, 4,257 significant DE transcripts were identified using the Ballgown R package (p < .01), of which 1,021 were protein-coding genes, 14 were known lncRNAs, and 661 were novel lncRNAs. Using WGCNA, a co-expression network of DE mRNAs and lncRNAs comprising 5 modules was generated to determine functional associations clusters. This study reveals a valuable sub-network comprising 8 hub genes, one known lncRNA and 5 novel lncRNAs in the major module. These hub genes are associated with blood pressure regulation, generation of reactive oxygen species and metabolism. The analysis of co-expressed genes thus provides a basis for the regulatory mechanisms in PA in Yaks and for the detection of additional genes between cross-breed and parent populations.

Dynamic characteristics of the mitochondrial genome in SCNT pigs.

Most animals generated by somatic cell nuclear transfer (SCNT) are heteroplasmic; inheriting mitochondrial genetics from both donor cells and recipient oocytes. However, the mitochondrial genome and functional mitochondrial gene expression in SCNT animals are rarely studied. Here, we report the production of SCNT pigs to study introduction, segregation, persistence and heritability of mitochondrial DNA transfer during the SCNT process. Porcine embryonic fibroblast cells from male and female Xiang pigs were transferred into enucleated oocytes from Yorkshire or Landrace pigs. Ear biopsies and blood samples from SCNT-derived pigs were analyzed to characterize the mitochondrial genome haplotypes and the degree of mtDNA heteroplasmy. Presence of nuclear donor mtDNA was less than 5% or undetectable in ear biopsies and blood samples in the majority of SCNT-derived pigs. Yet, nuclear donor mtDNA abundance in 14 tissues in F0 boars was as high as 95%. Additionally, mtDNA haplotypes influenced mitochondrial respiration capacity in F0 fibroblast cells. Our results indicate that the haplotypes of recipient oocyte mtDNA can influence mitochondrial function. This leads us to hypothesize that subtle developmental influences from SCNT-derived heteroplasmy can be targeted when using donor and recipient mitochondrial populations from breeds of swine with limited evolutionary divergence.

Method to design a live coral cover sensitive index for multispectral satellite images.

Live coral cover (LCC) is regarded as the most efficient indicator of coral reef health. However, LCCs are usually sampled with standardized transect or photo quadrat techniques in field, which are incomplete and labour-intensive. To overcome such difficulties, we study a model to transfer the pixels of multispectral satellite images to quantitative LCCs. The idea is to extend band ratio-based (BR) indices to a novel index constructed using the ratio of different linear combinations (RDLC) of band reflectance and water depths. On the basis of field surveyed LCCs, an empirical process is further proposed to solve the unknown parameters of this RDLC. This approach provides new thinking for designing LCC-sensitive indices for given multispectral satellite images. The experimental results on Weizhou Island and Palmyra Atoll demonstrate that the method is effective and feasible, where the mean relative errors (MREs) are improved from 45 to 56% for BRs to 23-29% for RDLCs for Weizhou Island.

Genome-wide identification of rubber tree (Hevea brasiliensis Muell. Arg.) aquaporin genes and their response to ethephon stimulation in the laticifer, a rubber-producing tissue.

BACKGROUND: Natural rubber, an important industrial raw material, is specifically synthesized in laticifers located inside the rubber tree (Hevea brasiliensis Muell. Arg.) trunk. Due to the absence of plasmodesmata, the laticifer water balance is mediated by aquaporins (AQPs). However, to date, the characterization of H. brasiliensis AQPs (HbAQPs) is still in its infancy. RESULTS: In this study, 51 full-length AQP genes were identified from the rubber tree genome. The phylogenetic analysis assigned these AQPs to five subfamilies, including 15 plasma membrane intrinsic proteins (PIPs), 17 tonoplast intrinsic proteins (TIPs), 9 NOD26-like intrinsic proteins (NIPs), 4 small basic intrinsic proteins (SIPs) and 6 X intrinsic proteins (XIPs). Functional prediction based on the analysis of the aromatic/arginine (ar/R) selectivity filter, Froger's positions and specificity-determining positions (SDPs) showed a remarkable difference in substrate specificity among subfamilies. Homology analysis supported the expression of 44 HbAQP genes in at least one of the examined tissues. Furthermore, deep sequencing of the laticifer transcriptome in the form of latex revealed a key role of several PIP subfamily members in the laticifer water balance, and qRT-PCR analysis showed diverse expression patterns of laticifer-expressed HbAQP genes upon ethephon treatment, a widely-used practice for the stimulation of latex yield. CONCLUSIONS: This study provides an important genetic resource of HbAQP genes, which will be useful to improve the water use efficiency and latex yield of Hevea.

ShRNA-mediated knock-down of CXCR7 increases TRAIL-sensitivity in MCF-7 breast cancer cells.

This study aims to investigate the effects of CXCR7-shRNA on TRAIL-mediated apoptosis and suppression of invasive migration and the underlying mechanisms. (1) We constructed CXCR-7-shRNA lentiviral vectors and confirmed their silencing efficiency in MCF-7 cells by RT-PCR analysis. (2) The effects of CXCR7 and/or TRAIL on cell proliferation were examined by MTT assay. (3) Trans well invasion assay was used to examine the effects of CXCR7 silencing and/or TRAIL on MCF-7 cell invasive migration. (4) Expression of Caspase-3, and Caspase-8, and MMP-2 and MMP-9 proteins was examined by Western blot analysis. (1) Viral titers were 2.95 × 10(8) TU/ml, 3.01 × 10(8) TU/ml, 3.26 × 10(8) TU/ml, and 3.08 × 10(8) TU/ml, respectively. (2) CHXR7 shRNAs markedly decreased CXCR7 mRNA expression in MCF-7 cells, among which CXCR7-shRNA-1 showed significantly higher rate of inhibition (P < 0.05). (3) Combination of TRAIL and CXCR7-shRNA-1 resulted in marked suppression of cell proliferation in time-dependent manner (P < 0.05). (4) Cell invasion capacity was inhibited in each experimental group as compared to blank control group at 48 h post treatments (P < 0.05). Among them, combination of TRAIL and CXCR7-shRNA had the highest inhibitory effect (P < 0.05). (5) Western blot analysis indicated that TRAIL alone does not affect CXCR7 expression, but either TRAIL + CXCR7 shRNA or CXCR7 shRNA alone markedly suppressed CXCR7 protein expression. Furthermore, combination of TRAIL and CXCR-7-shRNA significantly increased Caspase-3 and Caspase-8 expression and decreased MMP-2 and MMP-9 expression (P < 0.05). Knock-down of CXCR-7 expression leads to augmented TRAIL-mediated suppression of MCF-7 cell proliferation and invasion.

Authentication of animal signatures in traditional Chinese medicine of Lingyang Qingfei Wan using routine molecular diagnostic assays.

Lingyang Qingfei Wan produced by Beijing TongRenTang is a long-standing and popular medicine in China and international pharmaceutical markets. Concerns continue to be raised about the legality of usage of saiga antelope, which was defined as endangered species by Convention on International Trade in Endangered Species of Wild Fauna and Flora legislation and internal legislation in China. Therefore, the alternative pill in which substitutes saiga antelope with goat in the formula of Lingyang Qingfei Wan was developed. In order to authenticate the origin of animal contents in Lingyang Qingfei Wan and its alternative pill, molecular diagnostic assay was utilized by mtDNA polymorphism analysis. Four universal primer pairs containing mtDNA 12SrRNA, 16SrRNA, cytochrome b gene and cytochrome oxidase I were employed to obtain species-specific sequences of saiga antelope and goat, and multiple species-specific primer pairs for saiga antelope and goat were used to identify the animal origin in patent pills according to nucleotide polymorphisms between the two species. In additions, alternative techniques were attempted surrounding dilemmas of low concentration of target DNAs and presence of PCR-inhibitory substances in organic ingredients within complex pill. Results revealed that all species-specific primers could be successfully used for authentication of animal origin within complex pill, and sample preprocessing was critical during experimental manipulation. Internal positive control was an efficient and cost-effective way to assist in monitoring the potential interference from inhibitory substances which existed in the highly processed pills.

Family functioning in Chinese type 2 diabetic patients with and without depressive symptoms: a cross-sectional study.

BACKGROUND: Patients with depression or type 2 diabetes mellitus (T2DM) often have associated impaired family functioning. The purpose of this study was: (1) to explore the family functioning of T2DM patients with and without depressive symptoms and (2) to explore the relationship between depressive symptoms and family impairment in T2DM patients with depressive symptoms. This study used a cross-sectional design. SAMPLING AND METHODS: A sample of 32 patients with T2DM who had depressive symptoms and 229 patients with T2DM who did not have depressive symptoms completed the Chinese versions of the Family Assessment Device (FAD) and the Beck Depression Inventory. RESULTS: This study showed that there were differences in duration of diabetes and some FAD dimensions between T2DM patients with and without depressive symptoms (p < 0.01). There were also differences in the frequencies of FAD dimensions between T2DM patients with and without depressive symptoms (p < 0.01). Age, duration of diabetes and family function were predicting factors of depressive symptoms among T2DM patients (p < 0.01). CONCLUSIONS: The T2DM patients with depressive symptoms had more unhealthy FAD dimensions than the T2DM patients without depressive symptoms. The family functioning of T2DM patients with depressive symptoms was worse than that of T2DM patients without depressive symptoms. Age, duration of diabetes and some dimensions of FAD were associated with depressive symptoms in the T2DM patients.

Protein Lactylation Profiles Provide Insights into Molecular Mechanisms Underlying Metabolism in Yak.

Protein lysine lactylation, a recently discovered post-translational modification (PTM), is prevalent across tissues and cells of diverse species, serving as a regulator of glycolytic flux and biological metabolism. The yak (Bos grunniens), a species that has inhabited the Qinghai-Tibetan Plateau for millennia, has evolved intricate adaptive mechanisms to cope with the region's unique geographical and climatic conditions, exhibiting remarkable energy utilization and metabolic efficiency. Nonetheless, the specific landscape of lysine lactylation in yaks remains poorly understood. Herein, we present the first comprehensive lactylome profile of the yak, effectively identifying 421, 308, and 650 lactylated proteins in the heart, muscles, and liver, respectively. These lactylated proteins are involved in glycolysis/gluconeogenesis, the tricarboxylic acid cycle, oxidative phosphorylation, and metabolic process encompassing carbohydrates, lipids, and proteins during both anaerobic and aerobic glucose bio-oxidation, implying their crucial role in material and energy metabolism, as well as in maintaining homeostasis in yaks.

Quetiapine versus other atypical antipsychotics for schizophrenia.

BACKGROUND: In many countries, second-generation ('atypical') antipsychotic drugs have become the first-line drug treatment for people with schizophrenia. It is not clear how the effects of the various second-generation antipsychotic drugs differ. OBJECTIVES: To evaluate the effects of quetiapine compared with other second-generation (atypical) antipsychotic drugs in the treatment of people with schizophrenia and schizophrenia-like psychoses. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (May 2010), inspected references of all identified studies, and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing oral quetiapine with other oral forms of atypical antipsychotic medication in people with schizophrenia or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data, we calculated risk ratios (RRs) and their 95% confidence intervals (CIs) on an intention-to-treat basis based on a random-effects model. We calculated number needed to treat for an additional beneficial outcome (NNTB) where appropriate. For continuous data, we calculated mean differences (MDs), again based on a random-effects model. MAIN RESULTS: Efficacy data tended to favour the control drugs over quetiapine (Positive and Negative Syndrome Scale (PANSS) total score vs olanzapine: 11 RCTs, n = 1486, mean quetiapine endpoint score 3.67 higher, CI 1.95 to 5.39, low quality; vs risperidone: 13 RCTs, n = 2155, mean quetiapine endpoint score 1.74 higher, CI 0.19 to 3.29, moderate quality; vs paliperidone: 1 RCT, n = 319, mean quetiapine endpoint score 6.30 higher, CI 2.77 to 9.83, moderate quality), but the clinical meaning of these data is unclear. No clear mental state differences were noted when quetiapine was compared with clozapine, aripiprazole or ziprasidone. Compared with olanzapine, quetiapine produced slightly fewer movement disorders (7 RCTs, n = 1127, RR use of antiparkinson medication 0.51, CI 0.32 to 0.81, moderate quality) and less weight gain (8 RCTs, n = 1667, RR 0.68, CI 0.51 to 0.92, moderate quality) and glucose elevation, but increased QTc prolongation (3 RCTs, n = 643, MD 4.81, CI 0.34 to 9.28). Compared with risperidone, quetiapine induced slightly fewer movement disorders (8 RCTs, n = 2163, RR use of antiparkinson medication 0.5, CI 0.36 to 0.69, moderate quality), less prolactin increase (7 RCTs, n = 1733, MD -35.25, CI -43.59 to -26.91) and some related adverse effects but greater cholesterol increase (6 RCTs, n = 1473, MD 8.57, CI 4.85 to 12.29). On the basis of limited data, compared with paliperidone, quetiapine induced fewer parkinsonian side effects (1 RCT, n = 319, RR use of antiparkinson medication 0.64, CI 0.45 to 0.91, moderate quality) and less prolactin increase (1 RCT, n = 319, MD -49.30, CI -57.80 to -40.80) and weight gain (1 RCT, n = 319, RR weight gain of 7% or more of total body weight 2.52, CI 0.5 to 12.78, moderate quality). Compared with ziprasidone, quetiapine induced slightly fewer extrapyramidal adverse effects (1 RCT, n = 522, RR use of antiparkinson medication 0.43, CI 0.2 to 0.93, moderate quality) and less prolactin increase. On the other hand, quetiapine was more sedating and led to greater weight gain (2 RCTs, n = 754, RR 2.22, CI 1.35 to 3.63, moderate quality) and cholesterol increase when compared with ziprasidone. AUTHORS' CONCLUSIONS: Available evidence from trials suggests that most people who start quetiapine stop taking it within a few weeks (around 60%). Comparisons with amisulpride, sertindole and zotepine do not exist. Although efficacy data favour olanzapine and risperidone compared with quetiapine, the clinical meaning of these data remains unclear. Quetiapine may produce fewer parkinsonian effects than paliperidone, aripiprazole, ziprasidone, risperidone and olanzapine. Quetiapine appears to have a similar weight gain profile to risperidone, as well as clozapine and aripiprazole (although data are very limited for the latter two comparators). Quetiapine may produce greater weight gain than ziprasidone and less weight gain than olanzapine and paliperidone. Most data that have been reported within existing comparisons are of very limited value because of assumptions and biases within them. Much scope is available for further research into the effects of this widely used drug.

Family functioning assessed by self-reported and observer-reported ratings of depressed patients and their partners.

This study explored subjectively perceived and objectively rated family dysfunction using the self-report Family Assessment Device (FAD) and observer-rated McMaster Clinical Rating Scale (MCRS), respectively. Perceived differences in family functioning ratings between 86 depressed patients and their partners and the degree of agreement between the subjective and objective rating scales were analyzed. There were significant correlations for perceived family functioning between the patients and their partners. There were moderate to significant correlations between patients' perceptions on five of the seven dimensions of the FAD (excluding problem solving and roles) and those dimensions of the MCRS. Findings showed moderate to significant correlations between six dimensions of the FAD and MCRS, excluding problem solving. Results on the FAD and MCRS were significantly correlated and considered equivalent. This suggests that these two instruments can be used individually or in combination to provide a comprehensive understanding of family functioning of couples with a depressed partner.

Perceived family functioning in depressed Chinese couples: a cross-sectional study.

This study investigated family functioning in Chinese couples with a first episode of major depression, and in normal controls, and examined the association between depression severity and family impairment. Seventy-four patients with a first episode of major depression and 73 normal controls, together with their respective spouses, were assessed using the Family Assessment Device and Beck Depression Inventory. Patients with a first episode of major depression reported significantly higher Family Assessment Device scores for all dimensions compared with normal controls. Beck Depression Inventory scores were positively associated with Family Assessment Device scores for patients with a first episode of major depression for five dimensions, but not for affective responsiveness and affective involvement. A first episode of major depression was thus associated with impaired family functioning in Chinese families, and depression severity was positively associated with family impairment for the depressed patients. These findings indicate the importance of including family interventions in the treatment of Chinese patients with a first episode of major depression.

Functional study and epigenetic targets analyses of SIRT1 in intramuscular preadipocytes via ChIP-seq and mRNA-seq.

The SIRT1 epigenetic regulator is involved in hepatic lipid homoeostasis. However, the role of SIRT1 in regulating intramuscular fat deposition as well as the pathways and potential epigenetic targets involved remain unknown. Herein, we investigate SIRT1 function, its genome-wide epigenetic target profile, and transcriptomic changes under SIRT1 overexpression during yak intramuscular preadipocytes differentiation. To this end, we analysed the relationship between SIRT1 and intramuscular fat content as well as lipid metabolism-related genes in longissimus dorsi tissue. We found that SIRT1 expression negatively correlates with intramuscular fat content as well as with the expression of genes related to lipid synthesis, while positively correlating with that of fatty acid oxidation-involved genes. SIRT1 overexpression in intramuscular preadipocytes significantly reduced adipose differentiation marker expression, intracellular triacylglycerol content, and lipid deposition. Chromatin immunoprecipitation coupled with high-throughput sequencing of H3K4ac (a known direct target of SIRT1) and high-throughput mRNA sequencing results revealed that SIRT1 may regulate intramuscular fat deposition via three potential new transcription factors (NRF1, NKX3.1, and EGR1) and four genes (MAPK1, RXRA, AGPAT1, and HADH) implicated in protein processing within the endoplasmic reticulum pathway and the MAPK signalling pathway in yaks. Our study provides novel insights into the role of SIRT1 in regulating yak intramuscular fat deposition and may help clarify the mechanistic determinants of yak meat characteristics.