Effectiveness of Implementing Modified Early Warning System and Rapid Response Team for General Ward Inpatients.

This retrospective study assessed the effectiveness and impact of implementing a Modified Early Warning System (MEWS) and Rapid Response Team (RRT) for inpatients admitted to the general ward (GW) of a medical center. This study included all inpatients who stayed in GWs from Jan. 2017 to Feb. 2022. We divided inpatients into GWnon-MEWS and GWMEWS groups according to MEWS and RRT implementation in Aug. 2019. The primary outcome, unexpected deterioration, was defined by unplanned admission to intensive care units. We defined the detection performance and effectiveness of MEWS according to if a warning occurred within 24 h before the unplanned ICU admission. There were 129,039 inpatients included in this study, comprising 58,106 GWnon-MEWS and 71,023 GWMEWS. The numbers of inpatients who underwent an unplanned ICU admission in GWnon-MEWS and GWMEWS were 488 (.84%) and 468 (.66%), respectively, indicating that the implementation significantly reduced unexpected deterioration (p < .0001). Besides, 1,551,525 times MEWS assessments were executed for the GWMEWS. The sensitivity, specificity, positive predicted value, and negative predicted value of the MEWS were 29.9%, 98.7%, 7.09%, and 99.76%, respectively. A total of 1,568 warning signs accurately occurred within the 24 h before an unplanned ICU admission. Among them, 428 (27.3%) met the criteria for automatically calling RRT, and 1,140 signs necessitated the nursing staff to decide if they needed to call RRT. Implementing MEWS and RRT increases nursing staff's monitoring and interventions and reduces unplanned ICU admissions.

Effect of digital storytelling intervention on resilience, self-efficacy and quality of life among patients with non-small cell lung cancer (NSCLC): A randomized controlled trial.

OBJECTIVE: To verify and compare whether the digital stories could effectively improve the resilience, self-efficacy and quality of life of postoperative NSCLC patients. MATERIALS AND METHODS: A total of 90 participants at baseline were randomly assigned to two groups, 45 patients per group. The intervention group received the digital storytelling intervention which includes 4 videos on different topics: positive psychological quality, cultivating healthy living habits, establishing good social support, and insisting on scientific exercise, whereas the control group received only routine care. The resilience, self-efficacy, and quality of life were assessed at baseline (T0) (within 3 days before surgery), immediately after intervention (T1), one month after intervention (T2), and three months after intervention (T3). A linear mixed effects model was used to test the effects of the digital storytelling interventions on resilience, self-efficacy, and quality of life. RESULTS: The intervention group reported significantly greater improvements in resilience, self-efficacy, and quality of life (all P < 0.001) at follow-ups than the control group after controlling for age, gender, and education level as covariates. Moreover, the sensitivity analysis results are consistent with the per-protocol, that overall time × group interactions effects were significantly different in resilience, self-efficacy, and quality of life (all P < 0.001). CONCLUSION: The digital storytelling intervention based on lung cancer survivors' experience can effectively improve resilience, self-efficacy and quality of life in postoperative lung cancer patients. More comprehensive researches are needed to evaluate the longer-term impacts of the DST and its feasibility for those with more advanced cancer.

[Effect and mechanism of Jiedu Huoxue Decoction in regulating YAP/ACSL4 pathway to inhibit ferroptosis in treatment of acute kidney injury].

Jiedu Huoxue Decoction(JDHX), first recorded in the Correction on Errors in Medical Works by WANG Qing-ren, is an effective formula screened out from ancient formulas by the traditional Chinese medicine(TCM) master ZHANG Qi to treat acute kidney injury(AKI) caused by heat, toxicity, stasis, and stagnation. This paper elucidated the therapeutic effect of JDHX on AKI and probed into the potential mechanism from ferroptosis. Thirty-two male C57BL/6 mice were randomized into four groups(n=8): normal, model, and low-and high-dose JDHX. Since the clinical treatment of AKI depends on supportive or alternative therapies and there is no specific drug, this study did not include a positive drug group. The low dose of JDHX corresponded to half of clinically equivalent dose, while the high dose corresponded to the clinically equivalent dose. Mice were administrated with JDHX by gavage daily for 7 consecutive days, while those in the normal group and the model group were administered with the corresponding volume of distilled water. On day 5 of drug administration, mice in other groups except the normal group were injected intraperitoneally with cisplatin solution at a dose of 20 mg·kg~(-1) to induce AKI, and the normal group was injected with saline. All of the mice were sacrificed 72 h after modeling, blood and kidney samples were collected for subsequent analysis. The levels of serum creatine(Scr) and blood urea nitrogen(BUN) were measured by the commercial kits. The expression level of kidney injury molecule 1(KIM-1) in the serum was measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin(HE) staining, periodic acid-Schiff(PAS) staining, and Prussian blue staining were employed to observe the pathological changes, glycogen deposition, and iron deposition, respectively, in the renal tissue. In addition, the levels of glutathione(GSH), superoxide dismutase(SOD), and catalase(CAT) in the renal tissue were examined by biochemical colorimetry. Western blot was performed to determine the protein levels of acyl-CoA synthetase long chain family member 4(ACSL4), lysophosphatidylcholine acyltransferase 3(LPCAT3), and Yes-associated protein(YAP, a key molecule in the Hippo pathway) in the renal tissue. Immunohistochemistry was then employed to detect the location and expression of YAP in the renal tissue. Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR) was performed to measure the mRNA levels of ACSL4 and glutathione peroxidase 4(GPX4). Compared with the normal group, the model group showed elevated serum levels of Scr, BUN, and KIM-1. In the AKI model group, the tubular epithelial cells underwent atrophy and necrotic detachment, disappearance of brush border, and some tubules became protein tubules or experienced vacuole-like degeneration. In addition, this group presented widening of the interstitium or even edema, increased renal tubule injury score, and obvious glycogen and iron deposition in parts of the renal tissue. Moreover, the model group had lower GSH, SOD, and CAT levels, higher ASCL4 and LPCAT3 levels, and lower GPX4 expression and higher YAP expression than the normal group. Compared with the model group, high dose of JDHX effectively protected renal function, lowered the levels of Scr, BUN and KIM-1, alleviated renal pathological injury, reduced glycogen and iron deposition, and elevated the GSH, SOD, and CAT levels in the renal tissue. Furthermore, JDHX down-regulated the protein levels of ACSL4, LPCAT3, and YAP and up-regulated the level of GPX4, compared with the model group. In conclusion, JDHX can protect mice from cisplatin-induced AKI by inhibiting ferroptosis via regulating the YAP/ACSL4 signaling pathway.

The impact of squamous cell transformation on the prognosis of patients treated with radical nephroureterectomy.

BACKGROUND: Limited information is available for guiding the management of upper urinary tract (UUT) urothelial carcinoma with squamous differentiation (UC-SqD). We did not even know about the difference between pure urothelial carcinoma (UC) and UC-SqD in the UUT regardless of treatment policy and prognosis. Instead of direct comparisons against each other, we included the third UUT malignancy, squamous cell carcinoma (SCC). This three-way-race model allows us to more clearly demonstrate the impact of squamous cell transformation on patient outcomes in UUT malignancy. METHODS: We retrospectively analysed 327 patients with UC, UC-SqD, or SCC who underwent radical nephroureterectomy with bladder cuff excision (RNU) at Taichung Veterans General Hospital, Taichung, Taiwan, between January 2006 and December 2013. A Kaplan-Meier survival analysis was used to evaluate the relationship between patient outcomes and histology. Multivariate Cox proportional hazards modelling was also used to predict patient prognoses. RESULTS: The five-year postoperative cancer-specific survival (CSS) rates were 83.6% (UC), 74.4% (UC-SqD), and 55.6% (SCC), and the 5-year recurrence-free survival (RFS) rates were 87.7% (UC), 61.5% (UC-SqD), and 51.9% (SCC). UC patients had significantly better 5-year RFS than UC-SqD and SCC patients (P = 0.001 and P < 0.0001, respectively). Patients with pure UC had significantly better 5-year CSS than SCC patients (P = 0.0045). SCC or UC-SqD did not independently predict disease-specific mortality (HR 0.999, p = 0.999; HR 0.775, p = 0.632, respectively) or disease recurrence compared to pure UC (HR 2.934, p = 0.239; HR 1.422, p = 0.525, respectively). Age, lymphovascular invasion (LVI), and lymph node (LN) status independently predicted CSS, while pathological tumour stage, LN status, and LVI predicted RFS. CONCLUSIONS: SCC and UC-SqD are not independent predictors of survival outcomes in patients with UUT tumours. However, they are associated with other worse prognostic factors. Hence, different treatments are needed for these two conditions, especially for SCC.

Cytoplasmic FKBPs are involved in molting and metamorphosis through regulating the nuclear localization of EcR.

Molting and metamorphosis are important physiological processes in insects that are tightly controlled by ecdysone receptor (EcR) through the 20-hydroxyecdysone (20E) signaling pathway. EcR is a steroid nuclear receptor (SR). Several FK506-binding proteins (FKBPs) have been identified from the mammal SR complex, and are thought to be involved in the subcellular trafficking of SR. However, their roles in insects are poorly understood. To explore whether FKBPs are involved in insect molting or metamorphosis, we injected an FKBP inhibitor (FK506) into a lepidopteran insect, Spodoptera litura, and found that molting was inhibited in 61.11% of the larvae, and that the time for larvae to pupate was significantly extended. A total of 10 FKBP genes were identified from the genome of S. litura and were clustered into 2 distinct groups, according to their subcellular localization, with FKBP13 and FKBP14 belonging to the endoplasmic reticulum (ER) group and with the other members belonging to the cytoplasmic (Cy) group. All the CyFKBPs were significantly upregulated in the prepupal or pupal stages, with the opposite being observed for the ER group members. FK506 completely blocked the transfer of EcR to the nucleus under 20E induction, and significantly downregulated the transcriptional expression of many 20E signaling genes. A similar phenomenon was observed after RNA interference of 2 CyFKBPs (FKBP45 and FKBP12b), but not for FKBP13. Taken together, our data indicate that the cytoplasmic FKBPs, especially FKBP45 and FKBP12b, mediate the nuclear localization of EcR, thereby regulating the 20E signaling and ultimately affecting molting and metamorphosis in insects.

Robotic partial nephrectomy for renal tumor: The pentafecta outcomes of a single surgeon experience.

PURPOSE: This study investigated the oncological and functional surgical outcomes for patients with renal tumor who underwent robot-assisted partial nephrectomy (PN) by a single surgeon in Taiwan from 2006 to 2019. METHODS: This retrospective study assessed patients who underwent robot-assisted PN for renal tumor. Patient data were analyzed for age, sex, body mass index, operative time and total ischemic time, surgical margin (positive/negative), and surgical complications. To evaluate functional and oncological outcomes, achievement of trifecta, and pentafecta criteria was used. Trifecta criteria were defined as a negative surgical margin, no postoperative complications, warm ischemia time <25 min. Pentafecta criteria were the trifecta criteria, >90% preservation of estimated glomerular filtration rate (eGFR) preservation, and no stage progression of chronic kidney disease at 1-year follow-up. RESULTS: Of 101 patients who received robot-assisted PN, the most common type of renal tumor was clear cell renal cell carcinoma (RCC) (38%), followed by angiomyolipoma (26%). Patient characteristics were mean age 54.59 ± 13.8 years; mean RENAL Nephrometry score 6.63 ± 2.16; mean operative time 102.34 ± 50.06 min; and warm ischemia time 20.01 ± 14.12 min. The mean eGFR was 104.43 ± 31.73 mL/min/1.73 m2 preoperatively and 89.39 ± 32.3 mL/min/1.73 m2 postoperatively. Pathologic evaluation showed malignant tumors in 57 patients, among whom achievement of trifecta criteria occurred for 39 (68.42%) and pentafecta criteria for 18 (31.57%). Operation time was the only predictor for pentafecta achievement. CONCLUSION: Robotic PN is a safe and effective approach for patients with renal tumor that can preserve most renal function and achieve oncological control. Pentafecta criteria can be used to more clearly define the surgical outcome of RAPN.

Robot-assisted radical prostatectomy using hugo RAS system: The pioneer experience in Taiwan and Northeast Asia.

BACKGROUND: Among the novel robotic platforms, the Hugo RAS system is the second most studied platform, next to the da Vinci system, and we aim to address our experiences in radical prostatectomy (RP) with the Hugo RAS system. METHODS: We recorded our first 12 cases of prostate cancer undergoing RP with the Hugo RAS system. The median console time was 145 min and median hospital stay was 7 days. Hedge' g was applied to search for the cut-off case in four parameters in surgeries. RESULTS: Pre-console preparation was significantly improved after the first seven cases, and the console time was remarkably shortened after the first two cases. The intraoperative pause for trouble shooting was remarkably shortened after the first three cases. CONCLUSIONS: We found that RP with the Hugo RAS system was feasible, and the learning curve was short as surgeons may benefit from the previous experience with the da Vinci system.

[Leonurine inhibits ferroptosis in renal tubular epithelial cells by activating p62/Nrf2/HO-1 signaling pathway].

To investigate the protective effect and the potential mechanism of leonurine(Leo) against erastin-induced ferroptosis in human renal tubular epithelial cells(HK-2 cells), an in vitro erastin-induced ferroptosis model was constructed to detect the cell viability as well as the expressions of ferroptosis-related indexes and signaling pathway-related proteins. HK-2 cells were cultured in vitro, and the effects of Leo on the viability of HK-2 cells at 10, 20, 40, 60, 80 and 100 µmol·L~(-1) were examined by CCK-8 assay to determine the safe dose range of Leo administration. A ferroptosis cell model was induced by erastin, a common ferroptosis inducer, and the appropriate concentrations were screened. CCK-8 assay was used to detect the effects of Leo(20, 40, 80 µmol·L~(-1)) and positive drug ferrostatin-1(Fer-1, 1, 2 µmol·L~(-1)) on the viability of ferroptosis model cells, and the changes of cell morphology were observed by phase contrast microscopy. Then, the optimal concentration of Leo was obtained by Western blot for nuclear factor erythroid 2-related factor 2(Nrf2) activation, and transmission electron microscope was further used to detect the characteristic microscopic morphological changes during ferroptosis. Flow cytometry was performed to detect reactive oxygen species(ROS), and the level of glutathione(GSH) was measured using a GSH assay kit. The expressions of glutathione peroxidase 4(GPX4), p62, and heme oxygenase 1(HO-1) in each group were quantified by Western blot. RESULTS:: showed that Leo had no side effects on the viability of normal HK-2 cells in the concentration range of 10-100 µmol·L~(-1). The viability of HK-2 cells decreased as the concentration of erastin increased, and 5 µmol·L~(-1) erastin significantly induced ferroptosis in the cells. Compared with the model group, Leo dose-dependently increased cell via-bility and improved cell morphology, and 80 µmol·L~(-1) Leo promoted the translocation of Nrf2 from the cytoplasm to the nucleus. Further studies revealed that Leo remarkably alleviated the characteristic microstructural damage of ferroptosis cells caused by erastin, inhibited the release of intracellular ROS, elevated GSH and GPX4, promoted the nuclear translocation of Nrf2, and significantly upregulated the expression of p62 and HO-1 proteins. In conclusion, Leo exerted a protective effect on erastin-induced ferroptosis in HK-2 cells, which might be associated with its anti-oxidative stress by activating p62/Nrf2/HO-1 signaling pathway.

Cytoplasmic Hsp70s promote EcR transport into the nucleus by responding to various stimuli.

Metamorphosis is one of the most important physiological processes in insects, which is coordinated by juvenile hormone (JH) and 20-hydroxyecdysone (20E). Ecdysone receptor (EcR) is a steroid receptor (SR), which usually presents in cytoplasm and transfers into nucleus after binding to 20E. Heat shock proteins (Hsps) are suggested to be important members of the SR complex. However, their role in nucleocytoplasmic shuttle of the EcR remains unclear. In the present study, we found that apoptozole (Hsp70 inhibitor) suppressed the larval molting by decreasing the expression of ecdysone signaling genes. Two cytoplasmic (Cy) Hsp70s (Hsp72 and Hsp73) interacted with both EcR and ultraspiracle (USP, the heterodimer partner of EcR). By immunohistochemistry experiments, we revealed that CyHsp70 co-localized with EcR in the cytoplasm, and that both apoptozole and interfering of CyHsp70 significantly inhibited the process of EcR entering the nucleus under 20E induction, while reducing the expression of ecdysone signaling genes. Interestingly, the nuclear localization of EcR was also promoted by two other stimuli, including JH and heat stress, and this promotion was inhibited by apoptozole. This implies that various stimuli can induce EcR entry into the nucleus, and that this process is mediated by CyHsp70. Curiously, neither JH nor heat stress activated the ecdysone signaling genes; instead, they have a significant inhibitory effect on them. Taken together, it seems that Cytoplasmic Hsp70s promote EcR transport into the nucleus by responding to various stimuli, and that the biological effects of various stimuli passing through the EcR are different. Thus, our data provide a new viewpoint to understand the mechanism of nucleocytoplasmic shuttle of EcR.

Identification of Spodoptera frugiperda (Lepidoptera: Noctuidae) and its two host strains in China by PCR-RFLP.

The fall armyworm (FAW) Spodoptera frugiperda was first found in China in 2018. In other countries, FAW has evolved corn and rice strain biotypes. It is not possible to identify these strains based on morphology. In addition, FAW is very similar in appearance to several other common pests. These situations bring great challenges to the population management of FAW. In this study, we developed a rapid identification method based on PCR-RFLP to distinguish the two FAW strains and the FAW from other lepidopteran pests. A 697 bp mitochondrial cytochrome c oxidase I (COI) was cloned and sequenced from FAW, Spodoptera litura, Spodoptera exigua, and Mythimna separata. The COI fragments of these species revealed unique digestion patterns created by three enzymes (Tail, AlWN I, and BstY II). Thus, these four species can be distinguished from each other. The enzyme Ban I recognized a unique SNP site on a 638 bp triosephosphate isomerase (Tpi) fragment of the corn strain FAW. The Tpi fragment of the corn strain was cut into two bands. However, the rice strain could not be digested. Using this method, all 28 FAW samples collected from different host plants and locations in China were identified as the corn strain. This suggests that the rice strain has not yet invaded China. This method allows discrimination of FAW from other Lepidopteran pests and distinguishes the two FAW host strains.

An-Luo-Hua-Xian Pill Improves the Regression of Liver Fibrosis in Chronic Hepatitis B Patients Treated with Entecavir.

Background and Aims: Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis and cancer. As the effectiveness of antiviral therapy to reverse liver fibrosis is limited, We aimed to evaluate the effect of An-Luo-Hua-Xian pill (ALHX) on fibrosis regression in CHB patients treated with entecavir (ETV). Methods: Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX (ETV+ALHX) between October 1, 2013 and December 31, 2020. Demographic, laboratory, and liver histology data before and after 78 weeks of treatment were collected. The Ishak fibrosis score (F) was used and fibrosis regression required a decrease in F of ≥1 after treatment. Results: A total of 780 patients were enrolled, and 394 with a second liver biopsy after treatment were included in the per-protocol population, 132 in ETV group and 262 in ETV+ALHX group. After 78 weeks of treatment, the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients: 124/211 (58.8%) vs. 45/98 (45.9%), p=0.035. The percentage of patients with a decreased liver stiffness measurement (LSM) was higher in the ETV+ALHX group: 156/211 (73.9%) vs. 62/98 (63.%), p=0.056. Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression [odds ratio (OR)=1.94, p=0.018], and a family history of hepatocellular carcinoma was on the contrary. (OR=0.41, p=0.031). Conclusions: ETV combined with ALHX increased liver fibrosis regression in CHB patients.

Joint Effects of Prenatal Folic Acid Supplement with Prenatal Multivitamin and Iron Supplement on Obesity in Preschoolers Born SGA: Sex Specific Difference.

Prenatal maternal nutrient supplementation has been reported to be associated with offspring obesity, but the reports are inconsistent and have mainly ignored the differences between the total children population and children born small for gestational age (SGA). This study aimed to examine the joint effects of folic acid, iron, and multivitamin supplementation during pregnancy on the risk of obesity in preschoolers born SGA. A total of 8918 children aged 3-6.5 years born SGA were recruited from Longhua District in Shenzhen of China in 2021. Their mothers completed a structured questionnaire about the child's and parents' socio-demographic characteristics, maternal prepregnant obesity, and mothers' prenatal supplementation of folic acid, iron, and multivitamin. In addition, the children's current weight and height were measured by trained nurses. Logistic regression models were used to analyze the associations between prenatal supplementations and the current presence of childhood obesity. After controlling for potential confounders, the results of the logistic regression analysis showed that prenatal supplement of folic acid (OR = 0.72, 95% CI = 0.55~0.93) was associated with a lower likelihood of being an obese preschooler born SGA. In contrast, the ingestion of multivitamin or iron supplements during pregnancy did not seem to be related to the likelihood of childhood obesity in preschoolers born SGA. Moreover, cross-over analysis of prenatal folic acid and multivitamin obtained significant negative associations of prenatal folic acid supplement only (OR = 0.73, 95% CI = 0.55~0.97) and combination supplement of folic acid and multivitamin (OR = 0.67, 95% CI = 0.50~0.90) with obesity of preschoolers born SGA; while the cross-over analysis of prenatal folic acid and iron observed significant negative associations between obesity of preschoolers born SGA and a combination supplement of folic acid and iron (OR = 0.70, 95% CI = 0.52~0.96). Furthermore, the aforementioned significant associations were only found in girls and not in boys when the analyses were stratified by sex. Our findings suggest that the prenatal folic acid supplementation may decrease the risk of obesity in preschool girls born SGA, and that this effect may be modified by prenatal multivitamin or iron supplementation.

Parent-child interactions in early life mediating association between prenatal maternal stress and autistic-like behaviors among preschoolers.

A range of studies have shown that prenatal maternal stress (PNMS) exposure is associated with offspring autistic-like behaviors, however the potential pathways remain unexplored. This study aimed to evaluate the mediating role of parent-child interactions in early life in the association between PNMS exposure and preschoolers' autistic-like behaviors. Data from 65,928 child-parent dyads were obtained via a primary caregiver-reported questionnaire administered as part of the Longhua Child Cohort Study. To strengthen confidence in the reliability of the results, the analyses were initially conducted on a random selection of 70% of the total sample, and then validated on the remaining 30% of the sample. Analysis of covariance and multiple linear models were employed to estimate the associations between PNMS exposure, parent-child interactions in early life, and children's autistic-like behaviors. The results showed that PNMS exposure was positively associated with the presence of autistic-like behaviors at preschool age. The total indirect effect of the frequency of positive parent-child interactions in early life accounted for 9.69% or 8.99% of the variance of the association. Our findings indicate that parent-child interactions in early life might function as potential mediators of the association between PNMS and the increased risk of offspring autistic-like behaviors.

[Spatial and temporal variations of vegetation phenology and its response to urbanization in central Yunnan urban agglomeration, Southwest China]. / æ»‡ä¸­åŸŽå¸‚ç¾¤æ¤è¢«ç‰©å€™æ—¶ç©ºå˜åŒ–åŠå ¶å¯¹åŸŽå¸‚åŒ–çš„å“åº”.

Vegetation phenology is an important sensor that responds to environmental changes. Based on MOD13Q1 EVI data, we used the dynamic threshold method to extract vegetation phenological parameters of the central Yunnan urban agglomeration from 2001 to 2020, namely the start of growing season, the end of growing season, and the length of growing season, aiming to reveal the spatiotemporal variations in vegetation phenology and urban-rural differences. The results showed that vegetation phenology of the central Yunnan urban agglomeration from 2001 to 2020 generally showed a phenomenon of delayed start of growing season, delayed the end of growing season (0.66 days per year), and prolonged growing season. Compared with suburban and rural areas, growing season in urban areas in the past 20 years had started earlier (1.05 days per year), ended later (0.91 days per year), and thus growing season had been prolonged (1.79 days per year). Vegetation phenology showed significant difference on the gradient of urban, suburban, and rural areas. The start and the end of growing season of urban vegetation were the earliest, and the length of growing season was the longest, with the most significant changes in the urban areas and within the range of 0-2 km outward. The start of growing season in urban area was significantly earlier, the end of growing season was significantly delayed, and length of growing season was prolonged significantly with the increase of population density, per capita GDP, and the proportion of built-up area. The sensitivity of different phenological periods of vegetation and their duration to environmental changes varied on the gradient of urban, suburban and rural areas. Population density and proportion of built-up area in the study area played an important role in delaying the end of growing season of vegetation in the central Yunnan urban agglomeration.

WDR87 interacts with CFAP47 protein in the middle piece of spermatozoa flagella to participate in sperm tail assembly.

Spermatogenesis is a complex process that includes spermatogonia self-renewal, spermatocyte meiosis and spermatozoa assembly. Recent studies have revealed that WD40-repeat domain-containing (WDR) proteins play important roles in spermatocyte division, spermatozoa flagella assembly and head shaping. In this study, we investigated the expression pattern of WDR87 and found that it was highly expressed in the testis of both humans and mice. Immunofluorescence staining revealed that mouse WDR87 was distributed in the perinuclear cytoplasm of primary spermatocytes, secondary spermatocytes and round spermatids. In the spermiogenesis stage, with extension of the nucleus, WDR87 migrated to the manchette and finally localized to the middle piece of the spermatozoa tail. Furthermore, we identified a cilia- and flagella-associated protein, CFAP47, which interacted with WDR87 in the flagellar midpiece of the spermatozoa, suggesting that WDR87 may be associated with multiple morphological abnormalities of the flagella (MMAF). Subsequently, we screened gene mutations in seven MMAF individuals and found two novel mutations in CFAP47 (c.706G>A, Val236Met; c.1337C>T, Thr446Met) in one case. Immunoblotting and immunofluorescence revealed that CFAP47 was dramatically reduced in spermatozoa from the CFAP47-mutated man. Meanwhile, the expression of WDR87 was also significantly decreased, and weak signals were detected adjacent to the spermatozoa nuclei, indicating that CFAP47 was necessary for WDR87 transportation during spermatozoa flagella biogenesis. These data indicate that WDR87 is located in the middle piece of the sperm tail and interacts with CFAP47 to form a complex which is involved in spermatozoa tail assembly.

Long non-coding RNA MALAT1 promotes Th2 differentiation by regulating microRNA-135b-5p/GATA-3 axis in children with allergic rhinitis.

Allergic rhinitis (AR) threatens patient survival. CD4+ T cells play key roles in AR progression. Long non-coding RNAs (lncRNAs) are key regulators of cell differentiation. Therefore, we investigated the molecular mechanism of the lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in AR. Expression levels of MALAT1, microRNA (miR)-135b-5p, interleukin-4 (IL-4), and GATA-binding protein 3 (GATA-3) in the nasal mucosa of AR patients were quantified. CD4+ T cells were isolated from the peripheral blood of healthy volunteers and treated with ovalbumin (OVA) and Th2 inducers. After MALAT1 and miR-135b-5p levels changed in CD4+ T cells, the proportion of IL-4-expressing cells and the levels of IL-4 and GATA-3 in OVA-induced CD4+ T cells were determined. Binding relationships among MALAT1, miR-135b-5p, and GATA-3 were predicted and verified. Rescue experiments were performed to confirm the role of the MALAT1/miR-135b-5p/GATA-3 axis in Th2 differentiation of CD4+ T cells. MALAT1, IL-4, and GATA-3 expression was upregulated, whereas miR-135b-5p expression was downregulated, in patients with AR. MALAT1 knockdown or miR-135b-5p overexpression in CD4+ T cells notably decreased the proportion of IL-4-expressing cells and downregulated GATA-3 and IL-4 expression in OVA-induced CD4+ T cells. MALAT1 and GATA-3 exhibited competitive binding toward miR-135b-5p. MALAT1 facilitated CD4+ T cell Th2 differentiation via the miR-135b-5p/GATA-3 axis. MALAT1 facilitated AR development by facilitating CD4+ T cell Th2 differentiation via the miR-135b-5p/GATA-3 axis. This study may provide guidance for clinical treatment of AR.

First Trimester of Pregnancy as the Sensitive Period for the Association between Prenatal Mosquito Coil Smoke Exposure and Preterm Birth.

Mosquito coils are efficient mosquito repellents and mosquito coil smoke (MCS) contributes to indoor air pollution. However, no prior population-based study has investigated whether prenatal MCS exposure is a risk factor for preterm birth (PTB) and whether exposure to MCS in different trimesters of pregnancy is associated with different levels of risk. The sample involved 66,503 mother-child dyads. Logistic regression models were used to examine the relationships between prenatal MCS exposure during different trimesters of pregnancy and PTB. We found that prenatal MCS exposure was associated with a greater likelihood of PTB (OR = 1.12, 95%CI: 1.05-1.20). The prenatal MCS exposure during the first trimester was associated with 1.17 (95%CI: 1.09-1.25) times the odds of being PTB, which was higher than exposure during the second trimester (OR = 1.11, 95%CI: 1.03-1.19) and during the third trimester (OR = 1.08, 95%CI: 1.01-1.16). In the stratified analysis, prenatal MCS exposure significantly increased PTB risk among girls but not among boys. Our results indicated that maternal MCS exposure during pregnancy was associated with PTB and that the first trimester might be the sensitive period. In light of these findings, public health interventions are needed to reduce prenatal exposure to MCS, particularly during the first trimester of pregnancy.

Design, synthesis and in vitro biological evaluation of marine phidianidine derivatives as potential anti-inflammatory agents.

Phidianidines A and B are novel marine indole alkaloids with various biological activities. Based on their potential anti-inflammatory properties, a series of phidianidine derivatives were designed, synthesized, and tested for their effects on IL-17A production in PMA/ionomycin-stimulated T-cell-lymphoma EL-4 cells. Compounds 9a and 22c exhibited excellent anti-inflammatory activity and low toxicity, with IC50 values of 7.7 µM and 5.3 µM for IL-17A production in PMA/ionomycin-stimulated EL-4 cells, respectively. Further mechanistic study showed that 9a could decrease the STAT3 phosphorylation at Y705 to inhibit IL-17A production in EL-4 cells, indicating its ability of preventing the differentiation of Th17 cells and their possible function. This research may give an insight for the discovery of marine indole alkaloid derived anti-inflammatory drug leads for the treatment of T cell-mediated diseases.

Critical window for the association between prenatal environmental tobacco smoke exposure and preterm birth.

Although environmental tobacco smoke (ETS) exposure is considered to be a severe public health problem and a modifiable risk factor for preterm birth (PTB), we still lack a comprehensive understanding of the PTB risk associated with trimester-specific prenatal ETS exposure. This study aimed to examine the accumulation of risk across trimester ETS exposure and the critical window of the association between maternal ETS exposure during pregnancy and PTB. A total of 63,038 mother-child pairs were involved in the analysis of the 2017 survey of Longhua Child Cohort Study. Information about socio-demographic characteristics, prenatal ETS exposure, and birth outcomes were collected using a self-report questionnaire. A series of logistic regression models were employed to assess the associations between prenatal ETS exposure and PTB. We found that maternal ETS exposure during pregnancy significantly increased the risk of PTB and this association increased with both the average level of daily ETS exposure and the number of trimesters of ETS exposure. Moreover, mothers who were initially exposed to ETS in the 1st trimester of pregnancy had significant higher risk of PTB (OR = 1.34, 95% CI: 1.25-1.44). Furthermore, mothers exposed to ETS in the 1st trimester only (OR = 1.26, 95%CI: 1.04-1.50), in both 1st and 2nd trimester (OR = 1.35, 95%CI: 1.08-1.67) and throughout pregnancy (OR = 1.35, 95%CI: 1.24-1.46) experienced a significantly high risk of PTB. Prenatal maternal ETS exposure during only the 2nd trimester also resulted in a high risk of PTB with marginal significance (OR = 1.33, 95% CI:0.78-2.13). To conclude, the 1st and early 2nd trimester might be the critical window for prenatal ETS exposure causing PTB.

Selaginellin Inhibits Melanogenesis via the MAPK Signaling Pathway.

Hyperpigmented skin diseases such as melasma, freckles, and melanosis usually mar the appearance of patients. Traditional herbal medicines are highly accepted in inhibiting skin pigmentation, with advantages of high efficiency, low cost, and low side effects. Selaginellin (SEL), one of the active compounds of selaginella, has been proved to be exhibit antineoplastic, antioxidant, antisenescence, and antiapoptosis activities. In this study, we found that SEL can inhibit melanogenesis in vitro and in vivo. A mechanism study found that SEL inhibits melanogenesis through inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway, then down-regulating the expression of microphthalmia-associated transcription factor (MITF) and downstream genes tyrosinase (TYR) and tyrosinase-related protein 2 (TYRP2). UVB-activated paracrine function of fibroblasts and keratinocytes promotes melanogenesis of melanocytes. Interestingly, SEL antagonizes UVB-activated paracrine function of fibroblasts and keratinocytes. These findings indicate that SEL can be a potential whitening compound to inhibit melanogenesis.