Visualizing Intracellular Organelle and Cytoskeletal Interactions at Nanoscale Resolution on Millisecond Timescales.

In eukaryotic cells, organelles and the cytoskeleton undergo highly dynamic yet organized interactions capable of orchestrating complex cellular functions. Visualizing these interactions requires noninvasive, long-duration imaging of the intracellular environment at high spatiotemporal resolution and low background. To achieve these normally opposing goals, we developed grazing incidence structured illumination microscopy (GI-SIM) that is capable of imaging dynamic events near the basal cell cortex at 97-nm resolution and 266 frames/s over thousands of time points. We employed multi-color GI-SIM to characterize the fast dynamic interactions of diverse organelles and the cytoskeleton, shedding new light on the complex behaviors of these structures. Precise measurements of microtubule growth or shrinkage events helped distinguish among models of microtubule dynamic instability. Analysis of endoplasmic reticulum (ER) interactions with other organelles or microtubules uncovered new ER remodeling mechanisms, such as hitchhiking of the ER on motile organelles. Finally, ER-mitochondria contact sites were found to promote both mitochondrial fission and fusion.

Painful physical symptoms and antidepressant treatment outcome in depression: a systematic review and meta-analysis.

BACKGROUND: Painful physical symptoms (PPS) are highly prevalent in patients with major depressive disorder (MDD). Presence of PPS in depressed patients are potentially associated with poorer antidepressant treatment outcome. We aimed to evaluate the association of baseline pain levels and antidepressant treatment outcomes. METHODS: We searched PubMed, Embase and Cochrane Library databases from inception through February 2023 based on a pre-registered protocol (PROSPERO: CRD42022381349). We included original studies that reported pretreatment pain measures in antidepressant treatment responder/remitter and non-responder/non-remitter among patients with MDD. Data extraction and quality assessment were performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses by two reviewers independently. The primary outcome was the difference of the pretreatment pain levels between antidepressant treatment responder/remitter and non-responder/non-remitter. Random-effects meta-analysis was used to calculate effect sizes (Hedge's g) and subgroup and meta-regression analyses were used to explore sources of heterogeneity. RESULTS: A total of 20 studies were included. Six studies reported significantly higher baseline pain severity levels in MDD treatment non-responders (Hedge's g = 0.32; 95% CI, 0.13-0.51; P = 0.0008). Six studies reported the presence of PPS (measured using a pain severity scale) was significantly associated with poor treatment response (OR = 1.46; 95% CI, 1.04-2.04; P = 0.028). Five studies reported significant higher baseline pain interference levels in non-responders (Hedge's g = 0.46; 95% CI, 0.32-0.61; P < 0.0001). Four studies found significantly higher baseline pain severity levels in non-remitters (Hedge's g = 0.27; 95% CI, 0.14-0.40; P < 0.0001). Eight studies reported the presence of PPS significantly associated with treatment non-remission (OR = 1.70; 95% CI, 1.24-2.32; P = 0.0009). CONCLUSIONS: This study suggests that PPS are negatively associated with the antidepressant treatment outcome in patients with MDD. It is possible that better management in pain conditions when treating depression can benefit the therapeutic effects of antidepressant medication in depressed patients.

Mental health conditions in patients with systemic lupus erythematosus: A systematic review and meta-analysis.

OBJECTIVES: The reported prevalence of mental health conditions (MHCs) in people with systemic lupus erythematosus (SLE) ranges widely. Whether MHCs are associated with increased risk of SLE or the outcomes of the disease is unclear. This paper aimed to conduct an umbrella and updated meta-analysis of MHCs in people with SLE and to identify whether MHCs are associated with the risk of SLE or patient outcomes. METHODS: We comprehensively searched PubMed, Web of Science, and Embase databases to identify relevant studies published before June 2023. Random-effect models were used to calculate the pooled prevalence and risk ratios for each MHC. RESULTS: 203 studies with 1485094 individuals were included. The most MHCs observed in patients with SLE were sleep disturbance (59.7% [95% CI, 52.4%-66.8%]) among adults and cognitive dysfunction (63.4% [95% CI, 46.9%-77.9%]) among children. We found that depressive disorders (RR = 2.30, 95% CI = 1.94-2.75) and posttraumatic stress disorder (RR = 1.93, 95% CI = 1.61-2.31) in the general population were significantly associated with an increased likelihood of developing SLE. Furthermore, concurrent MHCs were linked to unfavorable outcomes in patients with SLE, such as decreased quality of life, increased risk of unemployment, and other somatic comorbidities. CONCLUSION: Our study demonstrated a high prevalence of MHCs among patients with SLE. Individuals with pre-existing mental disorders exhibited an elevated susceptibility to developing SLE, and patients presenting with MHCs were at increased risk of experiencing suboptimal health and functional outcomes. Therefore, evaluating and preventing MHCs should be considered as an integral component of the comprehensive treatment strategy for SLE.

Comparison of totally robotic and totally laparoscopic gastrectomy for gastric cancer: a propensity score matching analysis.

BACKGROUND: With the improvements in laparoscopic or robotic surgical techniques and instruments, a growing number of surgeons have attempted to complete all digestive tract reconstruction intracorporeally; these procedures include totally robotic gastrectomy (TRG) and totally laparoscopic gastrectomy (TLG). This study aimed to evaluate the safety and feasibility of the TRG and compare the short-term outcomes of the TRG and TLG in patients with gastric cancer. METHODS: Between January 2018 and June 2023, 346 consecutive patients who underwent TRG or TLG at a high-volume academic gastric cancer specialty center were included. 1:1 propensity score matching (PSM) was performed to reduce confounding bias. The surgical outcomes, postoperative morbidity, and surgical burden were compared in PSM cohort. RESULTS: After PSM, a well-balanced cohort of 194 patients (97 in each group) was included in the analysis. The total operation time of the TRG group was significantly longer than that of the TLG group (244.9 vs. 213.0 min, P < 0.001). There was no significant difference in the effective operation time between the 2 groups (217.8 vs. 207.2 min, P = 0.059). The digestive tract reconstruction time of the TRG group was significantly shorter than that of the TLG group (39.4 vs. 46.7 min, P < 0.001). The mean blood loss in the TRG group was less than that in the TLG group (101.1 vs. 126.8 mL, P = 0.014). The TRG group had more retrieved lymph nodes in the suprapancreatic area than that in the TLG group (16.6 vs 14.2, P = 0.002). The TRG group had a lower surgery task load index (38.9 vs. 43.1, P < 0.001) than the TLG group. No significant difference was found in terms of postoperative morbidity between the 2 groups (14.4% vs. 16.5%, P = 0.691). CONCLUSION: This study demonstrated that TRG is a safe and feasible procedure, and is preferable to TLG in terms of invasion and ergonomics. The TRG may maximize the superiority of robotic surgical systems and embodies the theory of minimally invasive surgery.

M6A-induced transcription factor IRF5 contributes to the progression of cervical cancer by upregulating PPP6C.

Cervical cancer (CC) is a gynaecological malignancy tumour that seriously threatens women's health. Recent evidence has identified that interferon regulatory factor 5 (IRF5), a nucleoplasm shuttling protein, is a pivotal transcription factor regulating the growth and metastasis of various human tumours. This study aimed to investigate the function and molecular basis of IRF5 in CC development. IRF5, protein phosphatase 6 catalytic subunit (PPP6C) and methyltransferase-like 3 (METTL3) mRNA levels were evaluated by quantitative real-time (qRT)-polymerase chain reaction (PCR). IRF5, PPP6C, METTL3, B-cell lymphoma 2 and Bax protein levels were detected using western blot. Cell proliferation, migration, invasion, angiogenesis and apoptosis were determined by using colony formation, 5-ethynyl-2'-deoxyuridine (EdU), transwell, tube formation assay and flow cytometry assay, respectively. Glucose uptake and lactate production were measured using commercial kits. Xenograft tumour assay in vivo was used to explore the role of IRF5. After JASPAR predication, binding between IRF5 and PPP6C promoter was verified using chromatin immunoprecipitation and dual-luciferase reporter assays. Moreover, the interaction between METTL3 and IRF5 was verified using methylated RNA immunoprecipitation (MeRIP). IRF5, PPP6C and METTL3 were highly expressed in CC tissues and cells. IRF5 silencing significantly inhibited cell proliferation, migration, invasion, angiogenesis and glycolytic metabolism in CC cells, while induced cell apoptosis. Furthermore, the absence of IRF5 hindered tumour growth in vivo. At the molecular level, IRF5 might bind with PPP6C to positively regulate the expression of PPP6C mRNA. Meanwhile, IRF5 was identified as a downstream target of METTL3-mediated m6A modification. METTL3-mediated m6A modification of mRNA might promote CC malignant progression by regulating PPP6C, which might provide a promising therapeutic target for CC treatment.

Effect of GnRH Active Immunisation on Reproductive Performance of Male Sprague Dawley Rats.

To investigate the effect of active immunisation with gonadotropin-releasing hormone (GnRH) on the reproductive function in male Sprague Dawley (SD) rats, 24 42-day-old rats were randomly assigned to treatment with GnRH6-MAP, GnRH-OVA, a surgical castration group, and a blank control group. Each rat in the treatment groups was intramuscularly injected at 6, 8, and 10 weeks of age. The serum concentrations of testosterone (T), follicle-stimulating hormone (FSH), luteinising hormone (LH), and anti-GnRH antibodies were determined using enzyme-linked immunosorbent assays. The results showed that active immunisation with recombinant GnRH6-MBP and GnRH-OVA significantly increased the serum levels of anti-GnRH antibodies and reduced the serum concentrations of testosterone compared to the black control. Eight weeks after immunisation, the rats' testes were surgically removed for morphological evaluation, showing atrophy of the convoluted vasculature, relative emptying of the lumen, and insignificant differentiation of spermatogonial cells, which were increased in weight and volume compared with the blank control group. These findings indicated that active immunisation with GnRH can lead to testicular atrophy and reduce gonadal hormone concentrations, suggesting that GnRH is a highly effective immunogen.

Increasing Mass Transfer Resistance of MOFs as a Reverse Tuning Strategy to Achieve High-Resolution Gas Chromatographic Separation.

In separation science, precise control and regulation of the MOF stationary phase are crucial for achieving a high separation performance. We supposed that increasing the mass transfer resistance of MOFs with excessive porosity to achieve a moderate mass transfer resistance of the analytes is the key to conducting the MOF stationary phase with a high resolution. Three-dimensional UiO-67 (UiO-67-3D) and two-dimensional UiO-67 (UiO-67-2D) were chosen to validate this strategy. Compared with UiO-67-3D with overfast mass transfer and low retention, the reduced porosity of UiO-67-2D increased the mass transfer resistance of analytes in reverse, resulting in improved separation performance. Kinetic diffusion experiments were conducted to verify the difference in mass transfer resistance of the analytes between UiO-67-3D and UiO-67-2D. In addition, the optimization of the UiO-67-2D thickness for separation revealed that a moderate diffusion length of the analytes is more advantageous in achieving the equilibrium of absorption and desorption.

Association between sleep duration, sleep quality, bedtime and myopia: A systematic review and meta-analysis.

BACKGROUND: We performed a systematic review and meta-analysis to investigate the links between different sleep characteristics and risk of myopia. METHODS: PubMed, EMBASE, Web of Science, the Cochrane Library, PsycINFO, Wanfang, and CNKI were searched from inception to August 26, 2022, without any language restriction. Cross-sectional, case-control, or cohort studies that explored the association between sleep duration, sleep quality, bedtime, and myopia were included. NIH quality assessment tools were used to assess the methodological quality of included studies. Random-effect or fixed-effect models were used to pool the associations according to whether there is heterogeneity. RESULTS: A total of 31 studies with 205 907 participants were included in the final analysis (25 studies reporting sleep duration; four studies examining sleep quality and six studies evaluating bedtime). Compared to reference sleep duration, sufficient sleep duration (OR = 0.63, 95% CI = 0.51-0.78) was associated with a lower risk of myopia, and short sleep duration (OR = 1.66, 95% CI = 1.14-2.42) was associated with a higher risk of myopia. In addition, poor sleep quality (OR = 1.24, 95% CI = 1.05-1.47) was associated with a higher risk of myopia while late bedtime (OR = 1.30, 95% CI = 0.96-1.75) was not significantly associated with an increased risk of myopia. CONCLUSIONS: Alteration in sleep duration and sleep quality may influence the risk of myopia. Well-designed cohort studies are needed in future investigations to identify a causal relationship between different sleep characteristics and myopia.

Identification of a novel laccase gene EuLAC1 and its potential resistance against Botrytis cinerea.

In this study, a novel laccase gene, EuLAC1, was cloned from Eucommia ulmoides Oliver (E. ulmoides). An overexpression vector harboring the EuLAC1 was constructed and introduced into the tobacco (Nicotiana tabacum cv. Xanthi). The laccase activity, resistance to Botrytis cinerea (B. cinerea) and lignin level in wild-type and transgenic plants were thereafter investigated. Interestingly, the transgenic tobacco displayed a significantly higher laccase activity and resistance to gray mold as compared to the wild-type tobacco. Additionally, the lignin contents in the leaves and stems of the transgenic tobacco were significantly higher in comparison to the wild-type tobacco. Scanning electron microscopy was used to observe the cross sections of wild-type and transgenic tobacco stems and it was noted that the cell wall near the xylem catheter of the transgenic tobacco was substantially thicker and the outline clearer than that of the wild-type. Thus, the EuLAC1 gene can significantly increase laccase activity and lignin content in tobacco, leading to an increase in the physical defenses, thereby increasing tobacco resistance to gray mold.

Transfer of Invitro CD4 + T Cells with Hypomethylation of Perforin Promoter into Rats' Abdomens Causes Autoimmune Emphysema.

Our previous study suggested that hypomethylation of perforin promoter of CD4 + T cells might be involved in the pathogenesis of autoimmune emphysema of rats. Whether transfer of this kind of cells hypomethylated in vitro into naive immunocompetent rats also results in emphysema is unknown yet. To test the hypothesis above, thirty Sprague Dawley (SD) rats were randomly divided into three groups: a model group (n = 10), a normal control group (n = 10) and a sham operation group (n = 10). In the model group, spleen-derived CD4 + T cells of normal rats were treated with 5-azacytidine (5-Aza), complete Freund's adjuvant and Phosphate Buffered Saline (PBS), then transferred into naive immunocompetent rats. The normal control group was injected with CD4 + T lymphocytes from spleens of normal rats and the same amount of adjuvant and PBS as above. In sham operation group, normal rats were injected intraperitoneally with complete Freund's adjuvant and PBS. Histopathological evaluations (mean linear Intercept (MLI) and mean alveolar numbers (MAN)), anti-endothelial cell antibodies (AECA) in serum and bronchoalveolar lavage fluid (BALF), lung vascular endothelial growth factor (VEGF)), the apoptotic index (AI) of alveolar septal cells and the methylation levels of perforin promoter of CD4 + T cells were investigated. The levels of the methylation above and MAN were lower in the model group than in the control and the sham operation group, while the AECA in serum and BALF, VEGF, MLI and the AI were greater (all p < 0.05). The methylation levels of perforin promoter were positively correlated with the MAN (r = 0.747, p < 0.05) and negatively correlated with AI, AECA, MLI, and VEGF (r was -0.789, -0.746, -0.743, -0.660, respectively, all p < 0.05). This study suggests that transfer of invitro CD4 + T cells with hypomethylation of perforin promoter into rats causes autoimmune emphysema, possibly by increasing expression of VEGF and promoting alveolar septal cell apoptosis.

Altered expression of TMEM16A in colorectal carcinoma and its clinical significance.

TMEM16A has been reported to be over-expressed in some malignant tumors recently. The aim of this study was to investigate the role of TMEM16A in the progression of colorectal carcinoma (CRC) by detecting the expression of TMEM16A in CRC tissues, adjacent normal tissues, and adenoma tissues. Then, to investigate the relationship between TMEM16A expression and the clinicopathological features of patients with CRC.

TMEM16A overexpression indicates poor prognosis in colorectal cancer patients.

AIM: to investigate the relationship between TMEM16A and the clinicopathological features and prognosis of patients with colorectal cancer (CRC). METHODS: ninety-six patients with CRC confirmed by pathology after undergoing surgery at the First Affiliated Hospital of Dalian Medical University between June 2009 and December 2011 were enrolled and followed up. The expression of the TMEM16A protein in CRC was detected by immunohistochemistry in 96 cases. The relationship between the expression of the TMEM16A protein in CRC and the clinical features and clinical prognosis were analyzed. RESULTS: there was no correlation between the TMEM16A protein expression and gender, age, tumor location, size and degree of differentiation (p > 0.05). However, the expression of the TMEM16A protein was significantly associated with the depth of invasion, lymph node metastasis and Dukes stage (p < 0.05). Kaplan-Meier survival curves showed that CRC patients with high expression of the TMEM16A protein had a poorer overall survival compared with those with low expression levels (68.2 % vs 92.3 %, X2 = 9.892, p = 0.002). Multivariate Cox regression analysis showed that upregulation of the TMEM16A protein expression is an independent predictive factor for poor prognosis in patients with CRC (p < 0.05, RR = 6.467, 95 % CI: 1.777-23.538). CONCLUSIONS: the expression of the TMEM16A protein in CRC was associated with tumor invasion, lymph node metastasis and Dukes stage. High expression of the TMEM16A protein in CRC can be used as an independent predictive factor for a poor prognosis of patients with CRC.

Anterograde Viral Tracer Herpes Simplex Virus 1 Strain H129 Transports Primarily as Capsids in Cortical Neuron Axons.

The features of herpes simplex virus 1 (HSV-1) strain 129 (H129), including natural neurotropism and anterograde transneuronal trafficking, make it a potential tool for anterograde neural circuitry tracing. Recently anterograde polysynaptic and monosynaptic tracers were developed from H129 and have been applied for the identification of novel connections and functions of different neural circuitries. However, how H129 viral particles are transported in neurons, especially those of the central nervous system, remains unclear. In this study, we constructed recombinant H129 variants with mCherry-labeled capsids and/or green fluorescent protein (GFP)-labeled envelopes and infected the cortical neurons to study axonal transport of H129 viral particles. We found that different types of viral particles were unevenly distributed in the nucleus, cytoplasm of the cell body, and axon. Most H129 progeny particles were unenveloped capsids and were transported as capsids rather than virions in the axon. Notably, capsids acquired envelopes at axonal varicosities and terminals where the sites forming synapses are connected with other neurons. Moreover, viral capsids moved more frequently in the anterograde direction in axons, with an average velocity of 0.62 ± 0.18 µm/s and maximal velocity of 1.80 ± 0.15 µm/s. We also provided evidence that axonal transport of capsids requires the kinesin-1 molecular motor. These findings support that H129-derived tracers map the neural circuit anterogradely and possibly transsynaptically. These data will guide future modifications and improvements of H129-based anterograde viral tracers.IMPORTANCE Anterograde transneuronal tracers derived from herpes simplex virus 1 (HSV-1) strain 129 (H129) are important tools for mapping neural circuit anatomic and functional connections. It is, therefore, critical to elucidate the transport pattern of H129 within neurons and between neurons. We constructed recombinant H129 variants with genetically encoded fluorescence-labeled capsid protein and/or glycoprotein to visualize viral particle movement in neurons. Both electron microscopy and light microscopy data show that H129 capsids and envelopes move separately, and notably, capsids are enveloped at axonal varicosity and terminals, which are the sites forming synapses to connect with other neurons. Superresolution microscopy-based colocalization analysis and inhibition of H129 particle movement by inhibitors of molecular motors support that kinesin-1 contributes to the anterograde transport of capsids. These results shed light into the mechanisms for anterograde transport of H129-derived tracer in axons and transmission between neurons via synapses, explaining the anterograde labeling of neural circuits by H129-derived tracers.

Peripheral cytokine levels and response to antidepressant treatment in depression: a systematic review and meta-analysis.

Predicting antidepressant treatment response has been a clinical challenge for major depressive disorder (MDD). The inflammation hypothesis of depression suggests that cytokines play a key role in the pathophysiology of MDD and alterations in peripheral cytokine levels are associated with antidepressant treatment outcome. Present meta-analysis aimed to examine the association between baseline peripheral cytokine levels and the response to antidepressant treatment and to evaluate whether changes of cytokine levels were associated with the response to antidepressant treatment in patients with MDD. Human-based studies published in any language in peer-reviewed journals were systematically searched from the PubMed, Embase and Web of Science databases, from inception up to October 2018. The search terms included cytokine, depressive disorder and antidepressant and their synonyms. Case-control or case-case studies reporting on levels of IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, CRP, TNF-α, IFN-γ, GM-CSF, MIP-1α, and Eotaxin-1 in patients with MDD based on validated depression scales both before and after antidepressant treatment were included. Of 7408 identified records, 44 studies met inclusion. Standardized mean differences in each cytokine were evaluated, and random-effects meta-analyses were performed. MDD patients who responded to antidepressant treatment had lower baseline IL-8 levels than the nonresponders (Hedge's g = -0.28; 95%CI, -0.43 to -0.13; P = 0.0003; FDR = 0.004). Antidepressant treatment significantly decreased levels of TNF-α (Hedge's g = 0.60; 95%CI, 0.26-0.94; P = 0.0006; FDR = 0.004) only in responders, and responders showed significantly more decreased TNF-α levels compared with nonresponders (P = 0.046). These findings suggested that alterations in peripheral cytokine levels were associated with antidepressant treatment outcomes in MDD. Further investigations are warranted to elucidate sources of heterogeneity and examine the potentiality of using inflammatory cytokines as novel predictive markers for the pharmacological treatment of MDD.

A functional variant in the serotonin receptor 7 gene (HTR7), rs7905446, is associated with good response to SSRIs in bipolar and unipolar depression.

Predicting antidepressant response has been a clinical challenge for mood disorder. Although several genome-wide association studies have suggested a number of genetic variants to be associated with antidepressant response, the sample sizes are small and the results are difficult to replicate. Previous animal studies have shown that knockout of the serotonin receptor 7 gene (HTR7) resulted in an antidepressant-like phenotype, suggesting it was important to antidepressant action. In this report, in the first stage, we used a cost-effective pooled-sequencing strategy to sequence the entire HTR7 gene and its regulatory regions to investigate the association of common variants in HTR7 and clinical response to four selective serotonin reuptake inhibitors (SSRIs: citalopram, paroxetine, fluoxetine and sertraline) in a retrospective cohort mainly consisting of subjects with bipolar disorder (n = 359). We found 80 single-nucleotide polymorphisms (SNPs) with false discovery rate < 0.05 associated with response to paroxetine. Among the significant SNPs, rs7905446 (T/G), which is located at the promoter region, also showed nominal significance (P < 0.05) in fluoxetine group. GG/TG genotypes for rs7905446 and female gender were associated with better response to two SSRIs (paroxetine and fluoxetine). In the second stage, we replicated this association in two independent prospective samples of SSRI-treated patients with major depressive disorder: the MARS (n = 253, P = 0.0169) and GENDEP studies (n = 432, P = 0.008). The GG/TG genotypes were consistently associated with response in all three samples. Functional study of rs7905446 showed greater activity of the G allele in regulating expression of HTR7. The G allele displayed higher luciferase activity in two neuronal-related cell lines, and estrogen treatment decreased the activity of only the G allele. Electrophoretic mobility shift assay suggested that the G allele interacted with CCAAT/enhancer-binding protein beta transcription factor (TF), while the T allele did not show any interaction with any TFs. Our results provided novel pharmacogenomic evidence to support the role of HTR7 in association with antidepressant response.

Depression and anxiety in relation to cancer incidence and mortality: a systematic review and meta-analysis of cohort studies.

The link between depression and anxiety status and cancer outcomes has been well-documented but remains unclear. We comprehensively quantified the association between depression and anxiety defined by symptom scales or clinical diagnosis and the risk of cancer incidence, cancer-specific mortality, and all-cause mortality in cancer patients. Pooled estimates of the relative risks (RRs) for cancer incidence and mortality were performed in a meta-analysis by random effects or fixed effects models as appropriate. Associations were tested in subgroups stratified by different study and participant characteristics. Fifty-one eligible cohort studies involving 2,611,907 participants with a mean follow-up period of 10.3 years were identified. Overall, depression and anxiety were associated with a significantly increased risk of cancer incidence (adjusted RR: 1.13, 95% CI: 1.06-1.19), cancer-specific mortality (1.21, 1.16-1.26), and all-cause mortality in cancer patients (1.24, 1.13-1.35). The estimated absolute risk increases (ARIs) associated with depression and anxiety were 34.3 events/100,000 person years (15.8-50.2) for cancer incidence and 28.2 events/100,000 person years (21.5-34.9) for cancer-specific mortality. Subgroup analyses demonstrated that clinically diagnosed depression and anxiety were related to higher cancer incidence, poorer cancer survival, and higher cancer-specific mortality. Psychological distress (symptoms of depression and anxiety) was related to higher cancer-specific mortality and poorer cancer survival but not to increased cancer incidence. Site-specific analyses indicated that overall, depression and anxiety were associated with an increased incidence risks for cancers of the lung, oral cavity, prostate and skin, a higher cancer-specific mortality risk for cancers of the lung, bladder, breast, colorectum, hematopoietic system, kidney and prostate, and an increased all-cause mortality risk in lung cancer patients. These analyses suggest that depression and anxiety may have an etiologic role and prognostic impact on cancer, although there is potential reverse causality; Furthermore, there was substantial heterogeneity among the included studies, and the results should be interpreted with caution. Early detection and effective intervention of depression and anxiety in cancer patients and the general population have public health and clinical importance.

Regulation of dynein-dynactin-driven vesicular transport.

Most of the long-range intracellular movements of vesicles, organelles and other cargoes are driven by microtubule (MT)-based molecular motors. Cytoplasmic dynein, a multisubunit protein complex, with the aid of dynactin, drives transport of a wide variety of cargoes towards the minus end of MTs. In this article, I review our current understanding of the mechanisms underlying spatiotemporal regulation of dynein-dynactin-driven vesicular transport with a special emphasis on the many steps of directional movement along MT tracks. These include the recruitment of dynein to MT plus ends, the activation and processivity of dynein, and cargo recognition and release by the motor complex at the target membrane. Furthermore, I summarize the most recent findings about the fine control mechanisms for intracellular transport via the interaction between the dynein-dynactin motor complex and its vesicular cargoes.

Ambient fine particulate matter is associated with increased emergency ambulance dispatches for psychiatric emergencies.

AIMS: As a top ambient pollutant in urban area, fine particulate matter (PM2.5) has been associated with the occurrence and deterioration of many medical conditions, while limited studies have observed the association with psychiatric conditions. This study aimed to investigate the association between short-term PM2.5 exposure and psychiatric emergency events, and further explored the variation by age, sex and seasonal patterns, which have been suggested to be associated with both psychiatric risk and pollutant toxicity. METHODS: We used time-series analysis to investigate the association between short-term exposure of PM2.5 and emergency ambulance dispatches for psychiatric emergencies (EPE) (n = 158634) in Beijing, one of the top polluted cities in China during the study period between 2008 and 2014. Stratified analyses were conducted to examine the effects of age, sex and seasonal pattern. RESULTS: Every 10 µg/m3 increase of the PM2.5 concentration was associated with a 0.12% increase of the same-day overall EPE (95% CI: 0.03-0.22%, p = 0.013) and a 0.12% increase of the suicide-related EPE at lag 2 (95%CI: 0.01-0.24%, p = 0.041). The associations remained when adjusted for sunlight duration. An age effect was observed where children (age <18) showed a higher risk of suicide-related EPE after PM2.5 exposure compared to adults (18 ≤ age≤64). We did not observe evidence of effect modification by sex and season based on the results of stratified analysis. CONCLUSIONS: We found a positive association between acute PM2.5 exposure and increased psychiatric emergency presentations indicated by emergency ambulance dispatches data. Children were more vulnerable and might develop psychiatric problems including those leading to suicide. Public awareness of the health risks of PM2.5 is important to strengthen current efforts to reduce emissions.

The Calponin Family Member CHDP-1 Interacts with Rac/CED-10 to Promote Cell Protrusions.

Eukaryotic cells extend a variety of surface protrusions to direct cell motility. Formation of protrusions is mediated by coordinated actions between the plasma membrane and the underlying actin cytoskeleton. Here, we found that the single calponin homology (CH) domain-containing protein CHDP-1 induces the formation of cell protrusions in C. elegans. CHDP-1 is anchored to the cortex through its amphipathic helix. CHDP-1 associates through its CH domain with the small GTPase Rac1/CED-10, which is a key regulator of the actin cytoskeleton. CHDP-1 preferentially binds to the GTP-bound active form of the CED-10 protein and preserves the membrane localization of GTP-CED-10. Hence, by coupling membrane expansion to Rac1-mediated actin dynamics, CHDP-1 promotes the formation of cellular protrusions in vivo.

[Multi-modality MRI parameters correlate with the expression of the P504s protein in prostate cancer].

OBJECTIVE: To evaluate the expressions of P504s, 34ß-E12, and P63 proteins in PCa and the correlation between the parameters of multi-modality MRI and the expression of P504s. METHODS: We retrospectively analyzed the multi-modality MRI data on 43 PCa and 64 non-PCa patients. We obtained the signal intensity-time (SI-T) curves, maximum SI (SImax), time to SImax (Tmax), rate of maximum enhancement (Rmax), and automatically generated apparent diffusion coefficient (ADC) values by conventional, diffusion-weighted and dynamic contrast-enhanced MRI, and determined the expressions of P504s, 34ß-E12 and P63 in the prostatic tissues of the patients by immunohistochemistry. RESULTS: Statistically significant differences were observed between the PCa and non-PCa groups in the positive expressions of P504s (83.7% vs 0%, P < 0.05), 34ß-E12 (25.6% vs 91.0%, P < 0.05) and P63 (25.6% vs 86.0%, P < 0.05) in the prostatic tissue, the ADC value (ï¼»0.83 ± 0.22ï¼½ vs ï¼»1.34 ± 0.28ï¼½ ×10－3mm2/s, P < 0.05), Tmax (ï¼»21.30 ± 10.78ï¼½ vs ï¼»50.22 ± 36.31ï¼½ s, P < 0.05), SImax (ï¼»1.75 ± 0.39ï¼½% vs ï¼»1.24 ± 0.41ï¼½%, P < 0.05), and Rmax (ï¼»20.20 ± 15.50ï¼½% vs ï¼»7.98 ± 6.25ï¼½%, P < 0.05). The expression of P504s was correlated negatively with the ADC value and Tmax (r = －0.60 and －0.37, P < 0.01) but positively with SImax and Rmax (r = 0.50 and 0.45, P < 0.01). CONCLUSIONS: 　The parameters of multi-modality MRI are correlated with the expression of P504s in PCa and can be used as imaging biomarkers for predicting the degrees of its malignancy.