Enzyme modified biodegradable plastic preparation and performance in anaerobic co-digestion with food waste.

A modified biodegradable plastic (PLA/PBAT) was developed by through covalent bonding with proteinase K, porcine pancreatic lipase, or amylase, and was then investigated in anaerobic co-digestion mixed with food waste. Fluorescence microscope validated that enzymes could remain stable in modified the plastic, even after co-digestion. The results of thermophilic anaerobic co-digestion showed that, degradation of the plastic modified with Proteinase K increased from 5.21 ± 0.63 % to 29.70 ± 1.86 % within 30 days compare to blank. Additionally, it was observed that the cumulative methane production increased from 240.9 ± 0.5 to 265.4 ± 1.8 mL/gVS, and the methane production cycle was shortened from 24 to 20 days. Interestingly, the kinetic model suggested that the modified the plastic promoted the overall hydrolysis progression of anaerobic co-digestion, possibly as a result of the enhanced activities of Bacteroidota and Thermotogota. In conclusion, under anaerobic co-digestion, the modified the plastic not only achieved effective degradation but also facilitated the co-digestion process.

Association of serum uric acid with women's ovarian reserve: observational study and Mendelian randomization analyses.

OBJECTIVE: To investigate the association between serum uric acid and women's ovarian reserve. DESIGN: Retrospective observational study and Mendelian randomization study. SETTING: University-affiliated in vitro fertilization center. PATIENTS: Observational analyses were undertaken using data from 8,257 women with infertility who finished their first in vitro fertilization treatments between May 2017 and December 2021. Mendelian randomization analyses were based on genome-wide association summary statistics from several biobanks of predominantly European ancestries. INTERVENTIONS: Observational study involved testing log2 transformed serum uric acid levels (for linear, negative regression, and logistic regression analyses); original uric acid levels (for nonlinear association analyses). Mendelian randomization study involved testing genetically predicted uric acid levels. MAIN OUTCOME MEASURES: Biomarkers including antimüllerian hormone, basal antral follicle count, follicle-stimulating hormone, luteinizing hormone, ratio of follicle-stimulating hormone to luteinizing hormone, estradiol; indices of ovarian response to stimulation including poor ovarian response according to different criteria and oocyte yield. RESULTS: In retrospective observational study, all ovarian reserve-related outcomes demonstrated significant differences across serum uric acid quartiles. A two-fold uric acid increase was associated with increased antimüllerian hormone (adjusted ß = 0.69; 95% confidence interval [CI], 0.43-0.95), antral follicle count (adjusted incidence rate ratio = 1.10, 95% CI, 1.05-1.14), luteinizing hormone (adjusted ß = 0.53, 95% CI, 0.28-0.78), decreased risks of Bologna poor ovarian response (adjusted odds ratio = 0.97; 95% CI, 0.95-0.99) and groups 2-4 Poseidon poor ovarian response (group 2: 0.63, 0.56-0.71; group 3: 0.71, 0.65-0.78; group 4: 0.50, 0.46-0.55), whereas an increased risk of group 1 (1.26, 1.13-1.41). Nonlinear analyses showed a common inflection point at 320-340 µmol/L of uric acid. Interactions between uric acid and antimüllerian hormone and antral follicle count were presented in association with oocyte yield. Mendelian randomization results suggested a significant association between genetically predicted uric acid levels and antimüllerian hormone levels (ß = 0.08; 95% CI, 0.04-0.12) but none for uric acid in relation to polycystic ovarian syndrome or other related hormones. CONCLUSION: Higher uric acid levels were associated with better ovarian reserve and increased levels of antimüllerian hormone albeit an increased risk of unexpected poor ovarian response.

Potential mechanism of probiotic fermentation of Auricularia cornea var. Li./blueberry to reduce obesity induced by a high-fat diet.

The primary objective of this research was to investigate the effects of fermented Auricularia cornea var. Li./blueberry (FACB) on the gut microbiota of these super-large mouse models. The study, found that the groups who were given different amounts of FACB saw a significant reduction in their triglyceride and total cholesterol levels. There was a noteworthy increase in the ranks of high-density lipoprotein cholesterol (HDL-C) (P < 0.05). Furthermore, it was noted that FACB influenced the gut microbiota of the obese rats, improving in both the variety and quantity of short-chain fatty acids present in their intestines. This research provided the inaugural evidence of FACB's potential as an effective anti-obesity agent in a high-fat diet model, implying it could serve as a preventive measure against obesity.

Preparation of Phosphorylated Auricularia cornea var. Li. Polysaccharide Liposome Gel and Analysis of Its In Vitro Antioxidant Activity.

In this study, Auricularia cornea var. Li. polysaccharides (ACP) were used as the research object to prepare liposome gel and determine its antioxidant activity in vitro. Phosphorylated Auricularia cornea var. Li. polysaccharides (P-ACP) were prepared via the phosphorylation of ACP by the phosphate method. Additionally, phosphorylated Auricularia cornea var. Li. polysaccharide liposomes (P-ACPL) were prepared using a reverse evaporation method. Finally, phosphorylated Auricularia cornea var. Li. polysaccharide liposome gel (P-ACPLG) was prepared by dispersing the P-ACPL in the gel matrix. The results show that the phosphorylation of the P-ACP was 15.51%, the containment rate of the P-ACPL was 84.50%, the average particle size was (192.2 ± 3.3) nm, and the particle size distribution map had a homogeneous peak, resulting in the particle dispersion being uniform and the polydispersion index (PDI) being 0.134 ± 0.021. The average Zeta potential was (-33.4 ± 0.57) mV. In addition, the in vitro antioxidant activity of the P-ACPL was slightly higher than that of the ACP and P-ACP. After the P-ACPL was emulsified into P-ACPLG, the DPPH, hydroxyl radical clearance, and reducing the ability of P-ACPL remained unchanged. In general, the P-ACPLG prepared in this study has good antioxidant activity in vitro and can retain the antioxidant activity of P-ACPL in vitro well.

Influence of Auricularia cornea Polysaccharide Coating on the Stability and Antioxidant Activity of Liposomes Ginsenoside Rh2.

Liposomes (Lip) are microstructures containing lipid and aqueous phases for encapsulation and delivery of bioactivators. In this study, Ginsenoside Rh2 liposomes (Rh2-Lip) were prepared by a thin-film hydrated ultrasonic binding method. But they are not stable during storage. In addition, Rh2-Lip was wrapped with Auricultural cornea polysaccharide (ACP) and Chitosan (CS) as coating materials to improve stability. CS coating was used as a positive control. The particle sizes determined by dynamic light scattering (DLS) showed 183 ± 5.52 nm for liposomes, 197 ± 6.7 nm for Auricultural cornea polysaccharide coated liposomes (ACP-Rh2-Lip), and 198 ± 3.5 nm for Chitosan coated liposomes (CS-Rh2-Lip). The polydispersity index (PDI) of all liposomes was less than 0.3. Transmission electron microscopy (TEM) showed that ACP and CS were successfully encapsulated on the liposome surface. In vitro simulations of digestive stability in the gastrointestinal tract showed that ACP-Rh2-Lip and CS-Rh2-Lip were more stable in gastrointestinal fluids compared to Lip. The antioxidant experiment revealed that ACP-Rh2-Lip has greater antioxidant activity than Lip. The purpose of this study was to look into the effects of ACP-Rh2-Lip and to offer a reference for Ginsenoside Rh2 (Rh2) delivery.

The Psychometric Properties and Effectiveness of the Approach-Avoidance Job Crafting Scale among Chinese Kindergarten Teachers.

Job crafting is an important concept associated with many positive outcomes, particularly for kindergarten teachers. Specifically, job crafting can play a key role in improving kindergarten teachers' work experiences and reducing professional dysfunction, considering their stressful work environment. However, the existing scale that integrates the most accepted theories of job crafting-approach-avoidance theory-has not been examined for efficacy in a multicultural context. Thus, in this study, 1273 Chinese kindergarten teachers were selected as subjects to explore the psychological properties of the German version of the Approach-Avoidance Job Crafting Scale (AAJCS) within the Chinese culture context. The sample was randomly divided into two subsamples. In Sample 1 (N = 618), item analysis and confirmatory factor analysis (CFA) were conducted. In Sample 2 (N = 655), CFA, reliability, and criterion-related validity tests were conducted. The results showed that job crafting has two independent components, each containing four factors, and the third-order model had the best fit. The reliability and validity of the scale were good, suggesting that AAJCS is an appropriate tool for measuring job crafting in a kindergarten population. Future research is needed to test the validity and reliability of the AAJCS on other populations.

Clinical Value of Clip-and-Snare Assisted Endoscopic Submucosal Resection in Treatment of Rectal Neuroendocrine Tumors.

Introduction: The aim of the study was to introduce a new endoscopic technology, clip-and-snare assisted endoscopic submucosal resection (CS-ESMR), for treatment of rectal neuroendocrine tumors (NETs) and then to investigate the therapeutic value of CS-ESMR. Methods: In this retrospective study, 67 patients who underwent endoscopic treatment of rectal NETs from March 2017 to December 2021 were analyzed. According to the endoscopic resection methods (endoscopic mucosal resection [EMR], CS-ESMR, and endoscopic submucosal dissection [ESD]), the cases were divided into CS-ESMR group (27 cases), ESD group (31 cases), and EMR group (9 cases). The pathological R0 resection rate and the incidence of adverse events (bleeding and perforation) were compared among the three groups. Results: There was a significant difference about the pathological R0 resection between the CS-ESMR group and the EMR group and between the CS-ESMR group and the ESD group (both p < 0.05). Compared with ESD group, the procedure time, intraoperative bleeding, and the cost of CS-ESMR group are significantly decreased (p < 0.001, p < 0.05, p < 0.001, respectively). Conclusion: CS-ESMR may be a safe and effective treatment for rectal NETs with a diameter of less than 10 mm, without muscularis propria invasion and metastasis.

27­Gauge vitrectomy vs. 25­gauge vitrectomy in the management of proliferative diabetic retinopathy with preoperative intravitreal injection of conbercept.

Small-gauge vitrectomy has become popular due to its notable advantages, including less trauma, shortened convalescence and improved manoeuvrability. The aim of the present study was to compare the surgical outcomes of 27-gauge (27-G) vitrectomy with those of 25-gauge (25-G) vitrectomy in the management of proliferative diabetic retinopathy (PDR) with preoperative intravitreal injection of conbercept. The data of 48 consecutive patients with PDR (48 eyes) were retrospectively collected. The patients underwent conbercept intravitreal injection and pars plana vitrectomy with a 27-G group (23 eyes) or 25-G group (25 eyes) vitrectomy system. The operating time, suturing rate, endodiathermy rate, postoperative best-corrected visual acuity (BCVA), intraocular pressure (IOP) and complications were recorded. The mean postoperative BCVA at final follow-up was significantly improved compared with that at the baseline in both groups (P<0.001 for both). The differences in the mean BCVA changes between the two groups were not significant (P>0.99), and no differences were observed in the final central foveal thickness (P=0.51) between the two groups. The final IOP remained stable compared with that at the baseline in the 27-G group (P=0.36) and the 25-G group (P=0.05). The suturing rate was significantly decreased in the 27-G group compared with the 25-G group (P=0.04). There were no significant differences between the two groups in terms of the operating time (P=0.18), rate of endodiathermy use (P>0.99), iatrogenic retinal breaks (P=0.42) or postoperative recurrent vitreous haemorrhage (P>0.99). In addition, no case of ocular hypotony was observed in either group. In conclusion, 27-G vitrectomy was as efficient and safe as 25-G vitrectomy in the management of PDR in terms of operating time and complications. With reference to the literature, preoperative conbercept injection appears to assist in decreasing the incidence of intraoperative and postoperative complications.

Human and natural activities regulate organic matter transport in Chinese rivers.

Rivers connect terrestrial and aquatic ecosystems and export approximately 55.47 % of the net terrestrial carbon fixation. However, due to unavailable high-frequency monitoring data, litter is known about diurnal variation in riverine carbon transport on a national scale. Based on daily measurements between March 2021 and February 2022 at 1491 stations across China, this study clarified the spatiotemporal variations in riverine organic matter indicated by chemical oxygen demand (COD). Spatially, COD content showed a spatial pattern with high values in the northwest (p < 0.05), and COD flux was determined by water discharge (84.01 %). Human activities explained 73.20 % of the spatial variations in riverine COD content; in particular, agricultural planting significantly elevated riverine COD (r = 0.73, p < 0.01). Seasonally, 95.53 % of stations showed significant seasonal variations in COD contents (p < 0.05); 69.72 % (25.81 %) were identified as Type II (III) typically had the maximum (minimum) COD in summer (autumn). Moreover, except for human activities (41.08 ± 22.94 %), natural factors also contributed 47.41 ± 24.04 % to the seasonal variations. In summer, high temperatures increased COD by promoting algal proliferation at Type II stations; however, heavy precipitation diluted COD contents at Type III stations. In these cases, seasonal measurements were essential for estimating riverine organic matter transport, especially the values measured in spring and winter. This study has significant implications for managing the aquatic environment, estimating riverine organic matter transport, and balancing the global carbon budget.

Eff-3DPSeg: 3D Organ-Level Plant Shoot Segmentation Using Annotation-Efficient Deep Learning.

Reliable and automated 3-dimensional (3D) plant shoot segmentation is a core prerequisite for the extraction of plant phenotypic traits at the organ level. Combining deep learning and point clouds can provide effective ways to address the challenge. However, fully supervised deep learning methods require datasets to be point-wise annotated, which is extremely expensive and time-consuming. In our work, we proposed a novel weakly supervised framework, Eff-3DPSeg, for 3D plant shoot segmentation. First, high-resolution point clouds of soybean were reconstructed using a low-cost photogrammetry system, and the Meshlab-based Plant Annotator was developed for plant point cloud annotation. Second, a weakly supervised deep learning method was proposed for plant organ segmentation. The method contained (a) pretraining a self-supervised network using Viewpoint Bottleneck loss to learn meaningful intrinsic structure representation from the raw point clouds and (b) fine-tuning the pretrained model with about only 0.5% points being annotated to implement plant organ segmentation. After, 3 phenotypic traits (stem diameter, leaf width, and leaf length) were extracted. To test the generality of the proposed method, the public dataset Pheno4D was included in this study. Experimental results showed that the weakly supervised network obtained similar segmentation performance compared with the fully supervised setting. Our method achieved 95.1%, 96.6%, 95.8%, and 92.2% in the precision, recall, F1 score, and mIoU for stem-leaf segmentation for the soybean dataset and 53%, 62.8%, and 70.3% in the AP, AP@25, and AP@50 for leaf instance segmentation for the Pheno4D dataset. This study provides an effective way for characterizing 3D plant architecture, which will become useful for plant breeders to enhance selection processes. The trained networks are available at https://github.com/jieyi-one/EFF-3DPSEG.

A Challenging Transition: Factors Influencing the Effort-Reward Imbalance and Coping Strategies of Beginning Teachers in China.

Purpose: The initial phase can be difficult for teachers: beginning teachers are more likely to experience effort-reward imbalance (ERI) and its harmful effects. To reduce this risk, this study analyzed the factors that impact ERI among beginning teachers in China and investigated the coping strategies they use. Methods: The study used qualitative research methods to conduct semi-structured interviews with 20 beginning teachers. Each participant was interviewed for at least 40 minutes via an online platform. Results: The qualitative results showed that ERI among beginning teachers is influenced by the interaction of internal and external factors. The typical factors identified were organizational justice, leadership style, work motivation, and personality type. Beginning teachers in the Chinese context demonstrated a proactive attitude towards challenging situations and chose moderate approaches to cope with ERI. The effectiveness of these strategies varied due to individual differences and contextual factors. Conclusion: Overall, the findings emphasized the importance of addressing the challenges of beginning teachers to promote their well-being and improve the quality of education. Reducing the ERI of beginning teachers relies on a tripartite effort between society, schools and teachers themselves.

Sewage treatment decreased organic carbon resources in Hong Kong waters during 1986-2020.

Riverine organic carbon (OC) transport plays a role in regulating terrestrial and marine carbon pools and deteriorating coastal water quality. However, long-term OC transport in Asian rivers and its diffusion in marginal seas have remained unreported. This study reported the spatiotemporal variations in OC resources for Hong Kong waters, China, based on monthly monitoring data collected at 82 river stations and 94 ocean sites during 1986-2020. The station-based riverine OC varied spatially and was generally high, with a mean value of 1.4-52.0 mg/L. Moreover, along with improving water quality, OC at 97.6% of the river stations decreased during 1986-2020; overall, sewage treatment accounted for 83.4% of the exponential decrease in riverine OC (R2 = 0.68, p < 0.01). However, the reduction in riverine OC accounted for only 10.4% of the reduction in the marine five-day biochemical oxygen demand (BOD5), which occurred at 70.2% of the ocean sites, especially those closest to the shore. The linear reduction in the marine BOD5 (R2 = 0.24, p < 0.01) was mainly attributed to reduced OC input from the adjacent Pearl River (61.9%) and decreases in phytoplankton growth (19.0%). These results indicated that sewage treatment improved water quality and decreased OC resources in Hong Kong waters, which can serve as a sustainable development model for other coastal cities. This study has important implications for mitigating organic pollution in the context of human efforts to manage the water environment.

Effects of Salmonella Enteritidis infection on TLRs gene expression and microbial diversity in cecum of laying hens.

Salmonella Enteritidis (SE) is an important foodborne pathogen primarily causing human disease through contaminated food and water. In the current study, to assess the effect of Salmonella Enteritidis infection on the immune system and the microbial diversity of cecum and oviduct in chickens, twelve 24-week-old SE-negative White Leghorn layers were randomly selected and divided into 2 groups. Chickens in the challenge group were orally inoculated with SE, and chickens in the control group received an equal amount of sterilized Phosphate Buffered Saline solution. Serum and tissue samples (cecum, oviduct, ovary, liver, spleen, and pancreas) were collected at 7 days and 14 days post-infection (dpi). Quantitative PCR was used to detect the expression of Toll-like receptors (TLRs) in the cecum, oviduct and ovary. To understand the influence of SE infection on the microbial profile of the cecum and oviduct, microbial community composition of the cecal contents and oviducal contents were analyzed through 16S rRNA sequencing. Results showed that SE infection caused damage to the digestive organs, reproductive organs, and immune organs in laying hens. The expression of TLR1a, TLR1b, TLR2, TLR4, TLR5, TLR7 and TLR15 in the cecum were induced, and the content of IFN-γ, TNF-α, IL-2 and IL-18 in serum increased after SE infection. The composition of the microbial community significantly changed in cecal content, the dominant phylum of Firmicutes increased, and Bacteroidetes decreased significantly. In the oviduct, the microbial diversity became complicated, the dominant bacteria Faecalibacterium was significantly increased, and Bacteroides was significantly decreased. This study investigated the effects of SE infection in laying hens, including host innate immunity, the expression of TLRs, and changes in the composition of microbes in the cecum and reproductive tract. Our results may provide a scientific basis for the Salmonella Enteritidis control in chicken, the maintenance of oviduct function, and the guarantee of clean egg production.

Eutrophication and salinization elevate the dissolved organic matter content in arid lakes.

Dissolved organic matter (DOM) plays an essential role in the global lake carbon cycle. Understanding DOM composition and monitoring its spatiotemporal dynamics are of great significance for understanding the lake carbon cycle, controlling water pollution, and protecting water resources. However, previous studies have focused mainly on eutrophic freshwater lakes, with limited attention given to saline lakes. Based on in situ data collected in ten lakes in northwestern China, this study reported the changes in DOM components in different lake types. Parallel factor analysis (PARAFAC) was used to analyze the three-dimensional excitation emission matrix (EEMs) to obtain the DOM fluorescence components. The contributions of different environmental factors to the changes in DOM components were quantified by the generalized linear model (GLM). The results showed that the eutrophication index was significantly positively related to dissolved organic carbon (DOC) (R2 = 0.95, p < 0.01) and colored DOM (CDOM) (R2 = 0.96, p < 0.01) concentrations. Terrestrial humic-like and tryptophan-like components, which are highly correlated with human activities, explained 62% and 64% of the variations in DOC and CDOM, respectively. In sum, the contributions of human activities to the DOC and CDOM variations were 61% and 57%, respectively. Salinity also showed significant positive correlations with both DOC (R2 = 0.88, p < 0.01) and CDOM (R2 = 0.87, p < 0.01). Lake salinization led to increases in DOM concentration, and salinity contributed 20% and 16% to the DOC and CDOM variations, respectively. Therefore, human activities and salinity codetermined the DOM concentration and its composition in the western arid lakes. Based on these findings, this study proposed a feasible flowchart for remotely estimating DOM in saline lakes using satellite data. This study is significant for the long-term monitoring of the carbon cycle and the effective protection of lake water resources in saline lakes.

Anemia Is an Indicator for Worse Organ Damage Trajectories in Patients with Systemic Sclerosis: A Retrospective Study.

It is important for clinicians to determine the risk of worsening trajectories in SSc patients. The Scleroderma Clinical Trials Consortium (SCTC) Damage Index (DI) has been developed to quantify organ damage and shows good capability for mortality and morbidity prediction in patients with SSc. This retrospective study aimed to describe the SCTC-DI in Chinese SSc patients and to find features predicting worse organ damage trajectories based on SCTC-DI. A total of 433 SSc patients who met the inclusion criteria in the Peking University Third Hospital (PKUTH-SSc) and People's Hospital SSc cohort (PKUPH-SSc) were recruited for our study. Organ damage was relatively mild in our Chinese SSc cohort compared to other cohorts, with a mean SCTC-DI of 5.21 ± 4.60. We used both SCTC-DI ≥ 6 and ≥4 to define the high burden of organ damage and established two risk models by the LASSO algorithm, which revealed good identification of high organ damage burden (AUC = 0.689, 95% CI 0.636 to 0.742, p < 0.001 in SCTC-DI ≥ 6 model; AUC = 0.694, 95% CI 0.641 to 0.746, p < 0.001 in modified SCTC-DI ≥ 4 model). The anemia index at the baseline was included in these two models and was also independently related to organ damage progression (HR = 1.75, 95% CI 1.16 to 2.66, p = 0.008). In addition, the presence of an anti-Scl-70 autoantibody was also a predictor of progression (HR = 1.91, 95% CI 1.22 to 2.99, p = 0.005). In conclusion, anemia at the baseline was an important indicator for worse organ damage trajectories in SSc patients. We recommend using hemoglobin as a potential biomarker to evaluate organ damage in SSc patients.

Human activities changed organic carbon transport in Chinese rivers during 2004-2018.

Rivers serve as regulators of global climate by releasing greenhouse gases, burying particulate carbon, and connecting different ecosystem carbon pools. However, long-term organic carbon (OC) transport features across different Asian rivers are not well known due to unavailable data. Based on routinely monitored environmental and hydrological data during 2004-2018, this study investigated the spatiotemporal variations in dissolved (DOC) and particulate OC (POC) transport across 41 rivers in China. Across different rivers, both DOC (1.35 - 16.8 mg/L) and POC (0.27 - 4.48 mg/L) concentrations covered wide ranges. The DOC content was high in the north and low in the south, with significantly higher (t test, p < 0.01) values for rivers north of 30°N (5.39 ± 3.66 mg/L vs. 2.39 ± 1.14 mg/L). Human activities greatly influenced the riverine DOC and POC distributions. The riverine ammonia nitrogen (NH+ 4-N) content was positively correlated with DOC (r = 0.81 and p < 0.01) and explained 85.59% of its spatial variation. High vegetation coverage had significant effects on decreasing the riverine POC content, with r = -0.55 and p < 0.05. During 2004-2018, water pollution prevention and control strategies decreased DOC concentrations in 60.98% of rivers; meanwhile, anthropogenic vegetation restoration and dam construction led to POC content decreases in 90.48% of rivers. Importantly, along with DOC and POC changes, increasing DOC/POC ratios were found in 90.48% of the rivers, with 42.86% being significant, which indicated that Chinese rivers are losing their Asian features of low DOC/POC ratios due to artificial disturbance. This study is significant for accurately quantifying greenhouse gas emissions, carbon burial, and OC export to estuaries by Chinese rivers.

Acetylshikonin exerts anti-tumor effects on non-small cell lung cancer through dual inhibition of STAT3 and EGFR.

BACKGROUND: Lung cancer is one of the most common types of malignant tumor. It has one of the highest morbidity and mortality rates worldwide, and approximately 85% of cases are non-small cell lung cancer (NSCLC). Clinically, several EGFR inhibitors have been used to treat NSCLC, but resistance can develop. Studies have shown that cross talk between signal transducer and activator of transcription 3 (STAT3) and epidermal growth factor receptor (EGFR) can mediate drug resistance. Acetylshikonin has obvious antitumor effects, but the mechanism of action is still unclear. PURPOSE: To analyze the antitumor activity of acetylshikonin in lung cancer and clarify its molecular mechanism. METHODS: Methyl thiazolyl tetrazolium (MTT), colony formation and 5-ethynyl-2'-deoxyuridine (EDU) assays were performed to examine the effects of acetylshikonin in inhibiting the proliferation of NSCLC cells (PC-9, H1975 and A549). Scratch wound and transwell assays were used to evaluate the migration and invasion of NSCLC cells. Flow cytometry was employed to determine whether acetylshikonin could induce apoptosis. Proteome sequencing was used to identify the targets of acetylshikonin. Immunofluorescence staining and western blotting were utilized to verify the inhibition of STAT3 and EGFR phosphorylation. A xenotransplantation model was established to evaluate the efficacy of acetylshikonin in nude mice. RESULTS: Our data demonstrated that acetylshikonin significantly decreased the survival rate of human NSCLC cells, increased the apoptotic rate and inhibited cell migration dose-dependently. Immunofluorescence staining and western blotting analyses revealed that acetylshikonin inhibited EGFR and STAT3 pathways. Acetylshikonin also inhibited tumor growth in a xenograft model better than inhibitors of EGFR and STAT3. CONCLUSION: Acetylshikonin has anti-cancer effects on NSCLC cells by inhibiting EGFR and STAT3, indicating that acetylshikonin may be a new antitumor drug to treat NSCLC.

Altered neural correlates of episodic memory for food and non-food cues in females with overweight/obesity.

Episodic memory formation is fundamental to cognition and plays a key role in eating behaviors, indirectly promoting the maintenance and acceleration of weight gain. Impaired episodic memory function is a hallmark of people with overweight/obesity, nevertheless, little research has been conducted to explore the effects of overweight/obesity on neural networks associated with episodic memory. The current study aimed to unravel the behavioral responses and neurocognitive mechanisms underlying the episodic memory for food and non-food cues in females with overweight/obesity. To explore this issue, a group of females with overweight/obesity (n = 26) and a group of age-matched females with healthy weight (n = 28) participated in a functional magnetic resonance imaging (fMRI) event-related episodic memory paradigm, during which pictures of palatable food and pictures of neutral daily necessities were presented. Whole-brain analyses revealed differential engagement in several neural regions between the groups during an episodic memory task. Specifically, compared to the healthy weight controls, females with overweight/obesity exhibited reduced brain activity in the temporal, parietal, and frontal regions during episodic memory encoding and successful retrieval of both food and non-food cues. Additionally, activation patterns in the left hippocampus and right olfactory cortex of females with and without overweight/obesity suggested that item memory changed according to the type of stimuli presented during item memory. Specifically, females with overweight/obesity showed greater engagement of the left hippocampus and right olfactory cortex when processing food cues, but less activation of the left hippocampus and right olfactory cortex when presented with non-food cues. Consistent with the obesity and suboptimal food-related decision theoretical model, these findings provide evidence of dissociation of the neural underpinnings of episodic memory in females with overweight/obesity and underline important effects of overweight/obesity on brain functions related to episodic memory.

Blockade LAT1 Mediates Methionine Metabolism to Overcome Oxaliplatin Resistance under Hypoxia in Renal Cell Carcinoma.

Hypoxic microenvironment and metabolic dysregulation of tumor impairs the therapeutic efficacy of chemotherapeutic drugs, resulting in drug resistance and tumor metastasis, which has always been a challenge for the treatment of solid tumors, including renal cell carcinoma (RCC). Herein, starting from the evaluation of methionine metabolism in RCC cells, we demonstrated that the increased methionine accumulation in RCC cells was mediated by L-type amino acid transporter 1 (LAT1) under hypoxia. Glutathione (GSH), as a methionine metabolite, would attenuate the therapeutic efficacy of oxaliplatin through chemical chelation. Reducing methionine uptake by LAT1 inhibitor JPH203 significantly enhanced the sensitivity of RCC cells to oxaliplatin by reducing GSH production in vitro and in vivo. Therefore, we proposed an effective and stable therapeutic strategy based on the combination of oxaliplatin and LAT1 inhibitor, which is expected to solve the resistance of RCC to platinum-based drugs under hypoxia to a certain extent, providing a meaningful insight into the development of new therapeutic strategies and RCC treatment.

Synergistic effects of gaseous pollutants on hospital admissions for cardiovascular disease in Liuzhou, China.

Previous studies demonstrated that short-term exposure to gaseous pollutants (nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O3)) had a greater adverse effect on cardiovascular disease. However, little evidence exists regarding the synergy between gaseous pollutants and cardiovascular disease (CVD). Therefore, we aimed to estimate the effect of individual gaseous pollutants on hospital admissions for CVD and to explore the possible synergistic effects between gaseous pollutants. Daily hospitalization counts for CVD were collected from January 1, 2014, to December 31, 2015. We also collected daily time series on gaseous pollutants from the Environment of the People's Republic of China, including NO2, SO2, and O3. We used distributed lag nonlinear models (DLNMs) to assess the association of individual gaseous pollutants on CVD hospitalization, after controlling for seasonality, day of the week, public holidays, and weather variables. Then, we explored the variability across age and sex groups. In addition, we analyzed the synergistic effects between gaseous pollutants on CVD. Extremely low NO2 and SO2 increase the risk of CVD in all subgroup at lag 7 days. The greatest effect of high concentration of SO2 was observed in male and the elderly (≥ 65 years) at lag 3 days. Greater effects of high concentration of O3 were more pronounced in the young (< 65 years) and female at lag 3 days, while the effect of low concentration of O3 was greater in male and the young (< 65 years) at lag 0 day. We found a synergistic effect between NO2 and SO2 for CVD, as well as between SO2 and O3. The synergistic effects of NO2 and SO2 on CVD were stronger in the elderly (≥ 65) and female. The female was sensitive to synergistic effects of SO2-O3 and NO2-O3. Interestingly, we found that there was a risk of CVD in the susceptible population even for gaseous pollutant concentrations below the National Environmental Quality Standard. The synergy between NO2 and SO2 was significantly associated with cardiovascular disease hospitalization in the elderly (≥ 65). This study provides evidence for the synergistic effect of gaseous pollutants on hospital admissions for cardiovascular disease.