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Abstract Background This study aims to analyze potential differences in clinicopathology, efficacy of neoadjuvant therapy (NAT), and clinical outcome among HER2-null, HER2-ultralow and HER2-low breast cancers. Methods Consecutive cases of HER2-negative breast cancer that received NAT were included. They were classified as HER2-null (no staining), HER2-ultralow (incomplete faint staining in ≤ 10% of tumour cells) and HER2-low (HER2-1 + or HER2-2+, in situ hybridisation negative). Subgroup analysis was performed based on the HER2 expression level. Results Out of 302 patients, 215 (71.19%) were HER2-low, 59 (19.54%) were HER2-ultralow, and 28 (9.27%) were HER2-null. In comparison to the HER2-ultralow group, the HER2-low group exhibited higher expression frequencies of ER (p

Objective To obtain the monitoring measurement range of quality indicators of red blood cells, plasma and derivatives and leukocyte-reduced apheresis platelets provided by blood stations in Hebei province, explore the distribution of monitoring values and the change of monitoring level, so as to further strengthen the homogenization construction of quality control laboratories in blood stations in Hebei. Methods In 2023, the sampling data of 12 blood stations in Hebei from 2015 to 2022 were collected, scatter plots were made and the range markers were set, and the "mean±SD" line was taken as the upper limit and lower limit of the measurement range. In 2024, the monitoring values in 2023 were added, and the changes of two measurement ranges were compared to analyze the stability and overall level. Results Comparison of the measurement range from 2015 to 2022 and the measurement range from 2015 to 2023 showed that the standard deviation of the content of deleukocyte suspension of red blood cells-hemoglobin, washed erythrocyte-hemoglobin, washed erythrocyte-supernatant protein, cryoprecipitate coagulation factor-FⅧ, fresh frozen plasma-FⅧ, leukocyte-reduced apheresis platelets-leukocyte residue and leukocyte-reduced apheresis platelet-red blood cell concentration decreased from 8.132 to 7.993, 6.252 to 6.104, 0.273 to 0.267, 57.506 to 56.276, 0.920 to 0.892, 0.653 to 0.644 and 2.653 to 2.603, respectively.The narrowing of the standard deviation range of the above items led to more concentrated monitoring values and reduced dispersion. Comparison of the measurement range from 2015 to 2022 and the measurement range from 2015 to 2023 showed that the mean value of leukocyte residue of the deleukocyte suspension of red blood cells, hemoglobin content of the wash erythrocyte, protein content of supernatant of the wash erythrocyte, hemolysis rate of the wash erythrocyte, FⅧ content of the cryoprecipitate coagulation factor, plasma protein content of the fresh frozen plasma, FⅧ content of the fresh frozen plasma, platelet content of the leukocyte-reduced apheresis platelets changed from 0.362 to 0.476, 44.915 to 44.861, 0.280 to 0.283, 0.137 to 0.142, 133.989 to 133.271, 60.262 to 60.208, 1.301 to 1.277 and 3.036 to 3.033, respectively, and was closer to the national standard line, which reflects an increase in the number of unqualified monitoring values or values close to the national standard line in 2023. The long-term qualified rate of coagulation items was low, and no improvement has been observed. The stability of biochemical items has been enhanced but overall deviation has occurred, with the average value close to the national standard line. The possibility of subsequent testing failure has increased. The counting items showed no obvious common characteristics. Conclusion The use of "mean±SD" in the analysis can visually display the distribution of monitoring values of different items in Hebei, forming an indicator measurement range covering the past nine years. It shows the characteristics of each item, and provides reference for subsequent quality control laboratory data analysis of each blood stations to takes active measures to improve the monitoring level.

Abstract Abnormalities in ether lipid metabolism as well as the formation of neutrophil extracellular traps have recently been recognized as detrimental factors affecting tumorigenesis and progression. However, the role of abnormal ether lipid metabolism in colorectal cancer (CRC) evolution has not been reported. Here we show that the lipid metabolism-related gene enoyl-CoA δ-isomerase 2 (ECI2) plays a tumor-suppressor role in CRC and is negatively associated with poor prognosis in CRC patients. We mechanistically demonstrate that ECI2 reduces ether lipid-mediated Interleukin 8 (IL-8) expression leading to decreased neutrophil recruitment and neutrophil extracellular traps formation for colorectal cancer suppression. In particular, ECI2 inhibits ether lipid production in CRC cells by inhibiting the peroxisomal localization of alkylglycerone phosphate synthase (AGPS), the rate-limiting enzyme for ether lipid synthesis. These findings not only deepen our understanding of the role of metabolic reprogramming and neutrophil interactions in the progression of CRC, but also provide ideas for identifying potential diagnostic markers and therapeutic targets for CRC.

Abstract Background Alzheimer’s disease (AD) is the most common neurogenerative disorder without effective treatments. Defects in mitochondrial complex I are thought to contribute to AD pathogenesis. The aim of this study is to explore whether a novel gene therapy transducing yeast complex I gene NDI1 can be used to treat AD with severely reduced complex I function in cell and animal models. Methods The differentiated human neural cells were induced by Aβ1–42 to establish the AD cell model, and adeno-associated virus serotype 9 (AAV9) was used to transduce yeast NDI1 into the cell model. Aβ1–42 was injected into the hippocampus area of the brain to establish the AD mouse model. AAV9-NDI1 was injected stereotaxically into the hippocampus area to test the therapeutic effect. Results The expressed yeast complex I had an ameliorating effect on the defective function of human complex I and cellular pathological characteristics in the AD cell model. Furthermore, AAV9-NDI1 gene therapy in the hippocampus had a therapeutic effect on various aspects of mitochondrial function, histopathological characteristics and neurological defects in the AD mouse model. In addition, AAV9-NDI1 injection into the hippocampus of normal mice did not cause any adverse effect. Conclusions Compensating mitochondrial complex I function with yeast NDI1 is effective for gene therapy in Aβ-induced AD cell and mouse models. The results of this study offer a novel strategy and approach for treating AD types characterized by complex I abnormalities.

Tubocapsicum anomalum, a Chinese medicinal plant rich in anti-tumor withanolides, requires efficient extraction methods. In this paper, an HPLC method was first established for the detection of withanolides, and gradient elution was carried out using a methanol–water solvent system. It was found that the content of withanolides was the highest in the leaves of T. anomalum, followed by the stems and fruits, and almost none in the roots. During the actual picking process, the quantity of leaves collected was relatively small, while the number of stems was the highest. Therefore, the Box-Behnken response surface method was used to optimize the ultrasonic-assisted extraction process of withanolides from the stems of T. anomalum. The optimal extraction conditions were determined as follows: the liquid–solid ratio was 20:1, the extraction solvent was 70 % ethanol, the ultrasonic power was 250 W, the ultrasonic time was 40 min, and the ultrasonic temperature was 50 °C. Under these conditions, the average yields of tubocapsenolide A (Te-A) and tubocapsanolide A (Ta-A) can reach 2.87 ± 0.12 mg/g and 1.18 ± 0.05 mg/g, respectively. We further compared extraction rates of two withanolides from different parts of T. anomalum using ultrasonic and traditional extraction methods. Ultrasonic extraction significantly increased rates, with the highest yields from leaves, followed by stems and fruits. The results show that ultrasonic optimization can improve extraction rate, reduce time, lower costs, enhance quality, and increase yield. Therefore, the optimized ultrasonic-assisted extraction process was adopted to extract the aerial parts of T. anomalum and separate the components. After optimization, the extract underwent several chromatographic separations to isolate eight previously undescribed withanolides (1–8) and two artificial withanolides (9–10), in addition to fifteen known compounds (11–25). Their structures were established through extensive spectroscopic data analysis. The compounds were evaluated for their antiproliferative effects against multiple cancer cell lines, including human hepatocellular carcinoma cells (HepG2, Hep3B, and MHCC97-H), human lung cancer cells (A549), human fibro-sarcoma cancer cells (HT1080), human chronic myeloid leukemia cells (K562), and human breast cancer cells (MDA-MB-231 and MCF7). Compounds 1–3, 5, 7, 11, 13, 15–16, and 22 displayed significant activity with IC50 values of 5.14–19.87 μM. The above results indicate that ultrasonic-assisted extraction technology can be used to obtain new withanolides more efficiently from T. anomalum, thereby enhancing the utilization rate of T. anomalum resources.

Abstract BackgroundPhysical therapy has demonstrated efficacy in managing nonspecific low back pain (NLBP) among patients. Nevertheless, the prevalence of NLBP poses a challenge, as the existing medical infrastructure may be insufficient to care for the large patient population, particularly in geographically remote regions. Telerehabilitation emerges as a promising method to address this concern by offering a method to deliver superior medical care to a greater number of patients with NLBP. ObjectiveThe purpose of this study is to demonstrate the physical and psychological effectiveness of a user-centered telerehabilitation program, consisting of a smartphone app and integrated sensors, for patients with NLBP. MethodsThis was a single-center, prospective, randomized controlled trial for individuals with NLBP for a duration exceeding 3 months. All participants were assigned randomly to either the telerehabilitation-based exercise group (TBEG) or the outpatient-based exercise group (OBEG). All participants completed a 30-minute regimen of strength and stretching exercises 3 times per week, for a total of 8 weeks, and were required to complete assessment questionnaires at 0, 2, 4, and 8 weeks. The TBEG completed home-based exercises and questionnaires using a telerehabilitation program, while the OBEG completed them in outpatient rehabilitation. The Oswestry Disability Index (ODI) served as the primary outcome measure, assessing physical disability. Secondary outcomes included the Numeric Pain Rating Scale, Fear-Avoidance Beliefs Questionnaire, and 36-item Short-Form Health Survey. ResultsIn total, 54 of 129 eligible patients were enrolled and randomly assigned to the study. The completion of all the interventions and assessments in the TBEG and OBEG was 89% (24/27) and 81% (22/27). The findings indicate that no statistical significance was found in the difference of ODI scores between the TBEG and the OBEG at 2 weeks (mean difference −0.91; odds ratio [OR] 0.78, 95% CI −5.96 to 4.14; PPPPP ConclusionsTelerehabilitation interventions demonstrate comparable therapeutic efficacy for individuals with NLBP when compared to conventional outpatient-based physical therapy, yielding comparable outcomes in pain reduction and improvement in functional limitations.

Chelidonii herba is a traditional Chinese medicinal herb with effects including antispasmodic, analgesic, antitussive, and bronchodilator properties. Alkaloids are the main bioactive ingredients in Chelidonii herba. In this study, a two-dimensional nuclear magnetic resonance (Heteronuclear Singular Quantum Correlation, HSQC-2D-NMR) technique was employed to quantitatively analyze the total alkaloid content and three major active alkaloid monomers in Chelidonii herba from eleven different sources. The quantification results of the three monomeric alkaloids were also verified using conventional quantitative control methods such as HPLC. Experimental findings indicate that the total alkaloid content is not directly correlated with the content of the three monomeric alkaloids. Furthermore, the content of any individual monomeric alkaloid does not accurately reflect the overall quality of Chelidonii herba. It was demonstrated that the 2D-Q-NMR NMR can be applied as an alternative method. While maintaining the same levels of accuracy and precision, the 2D-Q-NMR method is simpler to operate and provides more comprehensive results with higher reproducibility in some cases.

BackgroundSentinel lymph node metastasis (SLNM) is a critical factor in the prognosis and treatment planning for breast cancer (BC), as it indicates the potential spread of cancer to other parts of the body. The accurate prediction and diagnosis of SLNM are essential for improving clinical outcomes and guiding treatment decisions.ObjectiveThis study aimed to construct a Lasso regression model by integrating multimodal ultrasound (US) techniques, including US, shear wave elastography (SWE), and contrast-enhanced ultrasound (CEUS), to improve the predictive accuracy of sentinel lymph node metastasis in breast cancer and provide more precise guidance for clinical treatment.ResultsA total of 253 eligible samples were screened, of which 148 were group benign and 105 were group malignant. There were statistically significant differences (p < 0.05) between group malignant patients in terms of age, palpable mass, body mass index, distance to nipple, maximum diameter, blood flow, microcalcification, 2D border, 2D morphology, and 2D uniformity and group benign. The Lasso regression model was useful in the diagnosis of benign and malignant nodules with an AUC of 0.966 and in diagnosing SLNM with an AUC of 0.832.ConclusionIn this study, we successfully constructed and validated a Lasso regression model based on the multimodal ultrasound technique for predicting whether SLNM occurs in BCs, showing high diagnostic accuracy.

Objective Incomplete landslide timing information can result in inaccuracies in the temporal relationship between landslides and rainfall, consequently affecting the precision of a critical rainfall threshold model. Methods To address this issue, this study focuses on rainfall-induced landslides in the Wanzhou District of Chongqing from 1995 to 2015. The Henghe Township, lacking historical landslide data, serves as the verification area. We proposed a prediction model for the daily temporal probability of landslide occurrence on a certain day based on long short-term memory (LSTM) and a temporal convolutional network (TCN). This method was used to reconstruct the temporal information of rainfall-induced landslide events by simulating the nonlinear relationship between the duration of landslides and rainfall. After the reconstruction of temporal information, the landslide events were verified and selected and subsequently applied to a reasonable division of the E-D effective rainfall threshold curve to establish the landslide meteorological warning model. Results The results showed that the average temporal probability of rainfall-induced landslides predicted by the proposed method reached 90.33%, which was higher than that of the ANN (71.17%), LSTM (72.75%), and TCN (86.91%) models. Using temporal probabilities exceeding a 90% threshold, 18 data points, including 42 landslides in the verification area, are expanded to 201. Compared with using solely historical landslide events, the meteorological warning model based on expanded temporal information provides a more reasonable warning classification, and the effective warning rate at the severe warning level is increased by 42.86%. Conclusion This method can compensate for the shortage of landslide time information in field investigations and provide data support for early meteorological warning systems for rainfall-induced landslides, thus improving the accuracy of early meteorological warning systems.

Proteolysis targeting chimeras (PROTACs), as a novel therapeutic drug model, has received widespread attention from academia and the pharmaceutical industry. PROTAC technology has led researchers to focus on developing chemical biology tool properties due to the unique operating mechanism and protein dynamic regulatory properties. In recent years the rapid development of PROTAC technology has gradually made PROTACs an essential tool for target identification and validation. To further promote the application of PROTAC tools in drug discovery and basic medical science research, this review distinguished target identification and validation concepts. Furthermore, research progress in PROTAC technology was summarized.

Abstract Background Sequence variation produced by mutation provides the ultimate source of natural selection for species adaptation. Unlike nonsynonymous mutation, synonymous mutations are generally considered to be selectively neutral but accumulating evidence suggests they also contribute to species adaptation by regulating the flow of genetic information and the development of functional traits. In this study, we analysed sequence characteristics of ATP6, a housekeeping gene from 139 Phytophthora infestans isolates, and compared the fitness components including metabolic rate, temperature sensitivity, aggressiveness, and fungicide tolerance among synonymous mutations. Results We found that the housekeeping gene exhibited low genetic variation and was represented by two major synonymous mutants at similar frequency (0.496 and 0.468, respectively). The two synonymous mutants were generated by a single nucleotide substitution but differed significantly in fitness as well as temperature-mediated spatial distribution and expression. The synonymous mutant ending in AT was more common in cold regions and was more expressed at lower experimental temperature than the synonymous mutant ending in GC and vice versa. Conclusion Our results are consistent with the argument that synonymous mutations can modulate the adaptive evolution of species including pathogens and have important implications for sustainable disease management, especially under climate change.

ObjectivePrevious studies have confirmed a positive correlation between the Triglyceride-Glucose (TyG) index and future risk of diabetes. However, evidence of this association in non-obese young populations remains limited. This study aims to investigate the relationship between the TyG index and the future risk of diabetes among non-obese young adults.MethodsThis retrospective cohort study included 113,509 non-obese young adults from China and 9,549 from Japan. The mean age was 35.73 ± 6.38 years, and 56,469 participants (45.89%) were male. The median follow-up duration was 3.38 years. The association between baseline TyG index and risk of diabetes was examined using Cox proportional hazards regression models. Non-linear relationships between the TyG index and risk of diabetes were identified using cubic splines and smoothed curve fitting in the Cox models. Sensitivity and subgroup analyses were also conducted.ResultsAfter adjusting for covariates, the results indicated a positive correlation between the TyG index and risk of diabetes in non-obese young adults (HR=3.57, 95% CI: 2.92-4.36, P

Microorganisms in sediment can timely reflect the impact of anthropogenic disturbance. So far, sediment microorganism studies have primarily focused on assessing the impact of a specific type of anthropogenic disturbance, such as mining, domestic sewage and damming. However, there has been limited attention given to systematically investigating the responses of microbial communities to various typical anthropogenic disturbances within a singular watershed. In light of this, this study involved the collection of 33 superficial sediment samples from the Xinzhai River. Physicochemical properties of sediments were analyzed, and microbial communities were studied by using the Illumina high-throughput sequencing technology. The results informed that moderate level of disturbance contributing to enhanced community diversity. Under different types of anthropogenic disturbances, significant differences existed in microbial genera, which significantly affected by pH, total nitrogen (TN) and heavy metals (HMs). In addition, pronounced differences in low-abundance biomarkers occured at the genus level, indicating key biomarkers within the same watershed could serve as indicators of specific types of anthropogenic disturbances. Functional microorganisms in Xinzhai River were mainly associated with iron, sulfur and nitrogen cycling. Furthermore, functional taxa involved in sulfate-reducing bacteria (SRB) were more constrained by nutrients and displayed more positive response to disturbance of sewage. While functional taxa related to nitrification and methane oxidation were dominant in areas mainly disturbed by acid mine drainage (AMD). Damming exerted the most significant influence on community composition and versatile taxa. This study provides precious and comprehensive insights into how sediment microorganisms differential respond to different types and intensities of anthropogenic disturbances within the same watershed. Simultaneously, substantive evidence is furnished to corroborate the hypothesis that anthropogenic activities might alter microbial community structure by influencing a small portion of key taxa.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated neuropathy. While CIDP typically affects the peripheral nerves in the limbs, involvement of cranial nerves is atypical, and cases of muscle atrophy secondary to cranial nerve involvement are exceptionally rare. A 30-year-old female patient, who complained of numbness and weakness in her limbs, was diagnosed with CIDP after experiencing atrophy of the tongue and sternocleidomastoid muscles, along with tongue muscle fibrillation during a neurological examination. Additionally, the patient had hypothyroidism caused by Hashimoto's thyroiditis. Cerebrospinal fluid tests indicated albumincytological dissociation. Electrophysiological examination results confirmed the diagnosis of typical CIDP. Glucocorticoid treatment, a standard therapy for CIDP, led to a significant improvement in the patient's symptoms, including the regeneration of her tongue muscles. A literature review revealed only eight cases of CIDP with hypoglossal nerve involvement, and this case represents the first documentation of concurrent sternocleidomastoid muscle atrophy. Although muscle atrophy from cranial nerve involvement is infrequent in CIDP, the positive response to treatment is encouraging.

Background:Equus asinus L. [Equidae; Asini Corri Colla] (donkey-hide gelatin, E-Jiao) is a traditional Chinese medicine renowned for its exceptional blood-supplementing effect. However, the specific components that contribute to its efficacy remain elusive. This study aimed to demonstrate that peptides are responsible for E-Jiao’s blood-supplementing effect and to explore the specific peptides contributing to its efficacy.Methods: The low molecular weight peptides of E-Jiao (LMEJ) were obtained using an in vitro digestion method. LMEJ and peptides in the rat bloodstream were characterized by peptidomics analysis. The blood-supplementing effect of LMEJ was assessed using blood-deficient zebrafish and mouse models. The effect of the peptides detected in rat blood was evaluated using the same zebrafish model, and network pharmacology analysis was performed to investigate the underlying mechanisms.Results: A total of 660 unique peptides were identified within LMEJ. Both E-Jiao and LMEJ significantly alleviated myelosuppression in mice but only LMEJ attenuated myelosuppression in zebrafish. After the administration of E-Jiao to rats, 67 E-Jiao-derived peptides were detected in the bloodstream, 41 of which were identical to those identified in LMEJ. Out of these 41 peptides, five were synthesized. Subsequent verification of their effects revealed that two of them were able to alleviate myelosuppression in zebrafish. Network pharmacology study suggested that E-Jiao may exert a blood-supplementing effect by regulating signaling pathways such as JAK-STAT, IL-17 and others. These results indicated that peptides are at least partially responsible for E-Jiao’s efficacy.Conclusion: This study provides a crucial foundation for further exploration of the bioactive components of E-Jiao.

Objective Determining the rainfall threshold is of great significance in controlling the risk of rainfall-induced landslides. Methods A total of 98 rainfall-induced landslides in Quzhou, Zhejiang Province, were used to study the rainfall threshold. Based on the statistical analysis of the rainfall data from 1970 to 2019, the rainfall threshold models established by the I-D, E-D and E-I curves are compared and analyzed. Subsequently, a landslide meteorological warning double-index model with daily rainfall R0 and 5-day effective rainfall R5 as warning indices was established based on the I-D model. Finally, the rationality and reliability of the model were confirmed using historical rainfall and landslide data. Results The results show that: (1) I-D is better than E-D and E-I in predicting rainfall-induced landslides; (2) The double-index model reasonably forecasts the average annual warning times of red, orange and yellow landslides in Quzhou, which are 1.5, 3.2 and 9.3, respectively; 20 landslides can be accurately predicted by the double-index model, of which 15 landslides are red and orange, and the model has successfully predicted all eight landslides in 2014; (3) The 7 hysteretic landslides used to test the prediction ability of the model all fell into the warning area, including 3 orange, 3 yellow and 1 blue events. Conclusion The results proposed in this paper are helpful for the meteorological warning of landslides in Quzhou and provide new methods for government risk assessment and management.

The objective of this study was to assess the concurrent validity of the Kunwei force plate system in relation to variables during a counter-movement jump (CMJ) task, in comparison to the Kistler in-ground force plate system, which is considered the “gold standard”. Methods: In a single testing session, the Kunwei force plates were placed directly on top of the in-ground Kistler force plate. This allowed for the simultaneous collection of vertical ground reaction forces from 30 participants (male, age = 22.8 ± 2.8 years, body mass = 74.3 ± 12.3 kg, height 178.2 ± 4.6 cm) during CMJ tests. The consistency between force plate systems was assessed using ordinary least products regression (OLPR) with bootstrapped 95% confidence intervals and the Interclass Correlation Coefficient (ICC). Results: There was no fixed or proportional bias in the CMJ variables measured between the force plate systems. The variables exhibited a strong correlation across the force plates during the CMJ task (ICC > 0.950, p < 0.01). Conclusion: The findings of this study indicate that there was no statistical difference between the Kunwei and Kistler force plate systems when evaluating common CMJ strategy and outcome variables, which are considered the gold standard. Hence, the Kunwei force plate can be regarded as a reliable substitute for the established industry benchmark in evaluating the force–time characteristics of the CMJ. Researchers, athletes, and coaches have the option to utilize this affordable and portable choice as a substitute for the more expensive laboratory-based force plate system. This alternative allows for the precise measurement of CMJ performance and force–time variables.

This study analyzes panel data of Chinese cities from 2003 to 2018 as a sample in the context of the dual circulation strategy in China to ascertain the impact of urban healthcare development on medical collaborative innovation efficiency by using the GS2SLS method. Furthermore, it empirically examines the influence mechanism of regional healthcare development on medical collaborative innovation efficiency by using a threshold regression model. Additionally, we identified the heterogeneity of this impact in different cities. The results show the following: (1) There is a significant positive spatial correlation between regional healthcare development and medical collaborative innovation efficiency; (2) Under the dual circulation strategy, the regional investment level in international circulation has the most significant role in the overall strategy, and domestic circulation has been significantly improved after the launch of the innovation-driven strategy; (3) The results of the threshold test show that while domestic and international circulation promote the efficiency of collaborative innovation by 0.83, the promotion effect is more obvious under a higher regional healthcare development level. The research in this paper can provide specific guidance for the development of China’s healthcare industry under the background of dual-cycle strategy, and can also provide valuable reference for developing countries in the world.

Background: Reduced work readiness is associated with elevated turnover rates, necessitating efforts to enhance the positive work readiness of newly graduated nurses to alleviate the shortage in the nursing workforce. Research into the work readiness of recent nursing graduates in China is still in its infancy. Most studies employ quantitative research methods, and further exploration of the self-perception of work readiness among new nurses in China is required. Objectives: This study aimed to investigate genuine experiences and self-perceptions of work readiness among new graduate nurses. Design: A qualitative descriptive study. Methods: Sixteen new nurses from a provincial tertiary hospital in China were included in this study, which adhered to the consolidated criteria for reporting qualitative research (COREQ) checklist for reporting. The data collection process involved conducting semi-structured interviews from September to October 2021. Inductive content analysis was employed to analyze the interview data. Results: The study identified four themes encompassing new nurses' real-life experiences and self-perceptions of work readiness: psychological stress, emotional conflict, empathy fatigue, and ethical dilemmas. Psychological stress comprised three subthemes: knowledge and skill deficits, communication barriers, and fear. Empathy fatigue was primarily characterized by psychological and physical symptoms. Ethical dilemmas involved conflicts over differences in values and between clinical reality and standardized nursing practice. Conclusion: Drawing from the self-perceptions of work readiness among new nurses found in this study, nursing administrators and educators must enhance the existing transition support program for new nurses. Additionally, the establishment of individualized training programs is recommended to further improve the work readiness of new nurses.

Macrophytes are crucial in maintaining the equilibrium of aquatic ecosystems. However, the pattern of macrophyte-derived caffeic acid (CA) release under heavy metal stress is yet to be fully understood. More importantly, due to its functional groups, CA may be a precursor to the formation of disinfection by-products, posing threats to water ecology and even safety of human drinking water. This study analyzed the responses of CA released by Vallisneria natans (V. natans) and Pistia stratiotes (P. Stratiotes) when exposed to Cu2+ and Mn2+ stress. Additionally, the CA levels in two constructed wetland ponds were detected and the degradation kinetics of CA during chlorination were investigated. Results indicated that CA occurred in two constructed wetland ponds with the concentrations of 44.727 μg/L (planted with V. natans) and 61.607 μg/L (planted with P. Stratiotes). Notably, heavy metal stress could significantly affect CA release from V. natans and P. Stratiotes. In general, under Cu2+ stress, V. natans secreted far more CA than under Mn2+ stress, the level could reach up to 435.303 μg/L. However, compared to V. natans, P. Stratiotes was less affected by Cu2+ and Mn2+ stress, releasing a maximum CA content of 55.582 μg/L under 5 mg/L Mn2+ stress. Aquatic macrophytes secreted more CA in response to heavy metal stresses and protected macrophytes from harmful heavy metals. CA degradation followed the pseudo first-order kinetics model, and the chlorination of CA conformed to a second-order reaction. The reaction rate significantly accelerated as NaClO, pH, temperature and Br- concentration increased. A new pathway for CA degradation and a new DBP 2, 2, 3, 3-tetrachloropropanal were observed. These findings pointed at a new direction into the adverse effect of CA, potentially paving the way for new strategies to solve drinking water safety problems.

The distribution and migration routes of the most studied swan species, mute swans (Cygnus olor), in East Asia are largely unknown because most of those studies were conducted in Europe and North America. In 2016 and from 2021 to 2022, we deployed satellite tracking devices on 22 and 10 mute swans wintering at the Ili River, Xinjiang of Western China, and summering at Ulansuhai Lake, Inner Mongolia of Eastern China, to determine their migration routes. Eight environmental factors, namely, human population density, the shortest distance to the nearest transportation route, elevation, aspect, slope, air temperature, wind speed and gross primary productivity (GPP), were used to analyse the environmental differences at the stopover sites of swan populations between Eastern and Western China. Ebinur and Ulungur Lakes in Xinjiang of Western China and Kapchagay Reservoir and Sasykkol and Alakol Lakes in Eastern Kazakhstan were the summering sites for the Western Chinese swan population; for the Eastern Chinese swan population, in addition to the Yellow River Delta being identified as a wintering site, the Hongze Lake Region of Jiangsu and Danaoban Lake of Inner Mongolia in China were also identified for the first time as wintering and summering sites, respectively. We also found that human population density and GPP were crucial determinants of stopover duration in the Eastern and Western Chinese swan populations both in spring and in autumn. Our findings provide basic data for future research on mute swans in East Asia and will contribute to conservation action plan development through current conservation status evaluations of important summering, wintering and stopover sites along the migration routes of mute swans.

Objective To conduct the laboratory quality assessment between 12 blood stations in Hebei province, analyze the results and explore the accuracy and comparability of testing, so as to improve the level of testing ability and quality management. Methods With reference to the external quality assessment rules of National Center for Clinical Laboratories and combined with the instructions of quality assessment samples, daily testing process of the laboratories were assessed. The quality indicators include blood cell count (WBC, RBC, Hb, HCT, MCV, MCH, MCHC and PLT), biochemical items (TP) and coagulation parameters (FIB and FⅧ). Results There are still problems in laboratories in terms of personnel operation, instrument maintenance and the impact of different reagent batches, especially in biochemical items and coagulation parameters. The pass rate of biochemical items was the lowest, only 72.75%, and that of blood cell count was the highest, reaching 98.75%. Conclusion With the progress of the project, the quality monitoring level of daily blood sampling tests in the quality control laboratory of each blood station has been improved. However, it is still necessary for each laboratory to improve the testing ability and quality management to a higher level in Hebei.

ADP-ribosylation factor 6 (Arf6), a small G-protein of the Ras superfamily, plays pivotal roles in multiple cellular events, including exocytosis, endocytosis, actin remodeling, plasma membrane reorganization and vesicular transport. Arf6 regulates the progression of cancer through the activation of cell motility and invasion. Aberrant Arf6 activation is a potential therapeutic target. This review aims to understand the comprehensive function of Arf6 for future cancer therapy. The Arf6 GEFs, protein structure, and roles in cancer have been summarized. Comprehending the mechanism underlying Arf6-mediated cancer cell growth and survival is essential. The structural features of Arf6 and its efforts are discussed and may be contributed to the discovery of future novel protein-protein interaction inhibitors. In addition, Arf6 inhibitors and mechanism of action are listed in the table. This review further emphasizes the crucial roles in drug resistance and attempts to offer an outlook of Arf6 in cancer therapy.

This paper focuses on the research of the residential distribution network and take the community as the research object. With the structure of energy supply and consumption of the residential distribution network gradually shows the characteristics of diversity, based on the integrated energy system of electricity, heat, and natural gas network, the power consumption of the mobile communication network, the orderly charging and discharging behavior of electric vehicles and carbon emission limit are also considered. Load aggregator is introduced as the energy manager to arrange the energy purchase and schedule strategy. Taking the minimization of energy cost of the residential distribution network as the optimization goal, a low-carbon economic scheduling model of the residential distribution network based on multi-dimensional network integration is established. Numerical examples are simulated based on the data of an actual community in Shanghai. Simulation results show that the model built in this paper can effectively reduce the energy cost and carbon emission of the community, and the daily load curve is significantly smoothed by shaving peak load and filling valley load, furthermore, it can improve the flexibility of energy consumption in the community, and reduce the operation pressure of the distribution transformer, promote the cost-effective, low-carbon, and reliable operation of the residential distribution network.

The forest musk deer (Moschus berezovskii) is a national Class I protected wild animal in China, and the IUCN Red list classifies it as globally endangered. It has significant value in traditional Chinese medicine and spices. However, wild M. berezovskii has faced a severe population decline due to human hunting, habitat loss, and fragmentation. Thus, studying its population size and distribution pattern is of great importance to develop effective conservation measures. Here, we determined the optimal MaxEnt model and used stratified sampling and the fecal pile counting method to predict the population size and potential habitat distribution of wild M. berezovskii in Chongqing using 133 species distribution points and 28 environmental variables. The results were as follows: (1) When the optimal model parameters were RM = 3.5 and FC = LQHPT, it had high model prediction accuracy (AUC = 0.909 ± 0.010, TSS = 0.663). (2) Under various climatic, topographic, vegetation, and anthropogenic disturbance scenarios, M. berezovskii was primarily distributed in northern, eastern, southwestern regions of Chongqing, covering an area of approximately 5562.80 km2. (3) The key environmental factors affecting the potential habitat distribution of M. berezovskii were elevation (36.5%), normalized difference vegetation index (NDVI, 16.6%), slope (11.8%), and land-use type (7.6%), whereas climate and anthropogenic disturbance factors had relatively little influence. (4) A population estimation for M. berezovskii identified approximately 928 ± 109 individuals in Chongqing. We recommend prioritizing the preservation of high-altitude habitats and native vegetation to mitigate human interference and minimize road damage. In summary, our results can enhance the understanding of M. berezovskii distribution and provide a basis for effective conservation and management initiatives.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally since 2020. The nucleocapsid (N) protein plays a crucial role in the life cycle of SARS-CoV-2. Here, we established a method to screen inhibitors of N protein by using microscale thermophoresis assays to obtain potential anti-SARS-CoV-2 agents. We identified 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (N-17, a diphenylheptane) as a compound with outstanding inhibitory activity. We further validated the binding of N-17 to the N-terminal domain of N protein (N-NTD) by using drug affinity responsive target stability assays. We evaluated the ability of N-17 to bind N protein and predicted the affinity of N-17 to the N-NTD with molecular docking and molecular dynamics simulation. N-17 exhibited excellent anti-viral activity against HCoV-OC43 and SARS-CoV-2, with EC50 values of 0.16 ± 0.01 μM and 0.17 ± 0.07 μM, respectively. Thus, we discovered a novel SARS-CoV-2 inhibitor targeting the N protein and validated its anti-viral activity in vitro. Our results may contribute to the development of promising therapeutic agents for COVID-19.

In the present paper, the prediction of the performance of a centrifugal pump is investigated based on proper orthogonal decomposition (POD) reduced-order model (ROM). Firstly, the POD method is used to analyze the characteristics of the complex flow field inside the centrifugal pump, especially the eigenvalues of the velocity field and pressure field, and then the ROM of the flow field in the centrifugal pump is established then. After that, the established reduced-order model is used to predict the internal flow field. The results show that the POD mode field can reflect the spatial scale distribution of the flow field. The low-order flow field reflects the large-scale flow field structure, while the high-order flow field reflects the small-scale flow field structure. With the established ROM, the overall pump head (0D, 0-dimensional parameter) can be predicted with the relative error of less than 5%, and the standard root mean square error (normalized root mean square error, NRMSE) of pressure field and velocity field (3D, 3-dimensional parameter) is less than 4% and 8%, respectively. The efficiency and accuracy of both 0D and 3D parameters’ prediction motivate the fast prediction of multi-scale simulation of the large-scale industrial system in the future.

Mancozeb is an extensively consumed fungicide, which often leaves high residue levels on agricultural products. The conventional method for detecting mancozeb involves a time-consuming process using gas chromatography (GC) after a 2-hour water-bath acidolysis, resulting in low efficiency and recovery rates. This study developed a rapid method for detecting mancozeb in fruits and vegetables using microwave-assisted acidolysis and extraction coupled with GC analysis. Mancozeb underwent “one-pot” acidolysis to generate CS2 gas and was subsequently extracted from samples using microwave treatment, requiring only 50 seconds of pretreatment time. The average recoveries of mancozeb ranged from 81% to 112%. The limit of detection and limit of quantification were 0.003 and 0.01 mg kg−1, respectively. The scanning electron microscope imaging showed that strong cell crumpling after microwave treatment improved the acidolysis rate significantly, where the acidolysis rate was 91.8% for mancozeb. In addition, this method is rapid, simple, and precise for detecting residues of mancozeb and other dithiocarbamate fungicides.

The main severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protease (Mpro, also known as 3CLpro) plays a central role in virus replication, thereby constituting an appealing therapeutic target for coronavirus disease 2019 (COVID-19) treatment. In this study, we used recently reported crystal structures of SARS-CoV-2 Mpro complexed with small-molecule inhibitors. Using the established structure–activity relationships of small-molecule inhibitors of the Mpro of SARS-CoV-2, we used the Virtual Screening Workflow (with hydrogen bond constraints) implemented in Schrödinger Suite 2021 to screen approximately one million compounds in the ChemDiv compound library to identify potential novel noncovalent Mpro inhibitors. Our docking analysis yielded 65 promising lead compounds, the inhibitory activity of which against Mpro was assessed using a fluorescent SARS-CoV-2 Mpro inhibition assay. Notably, six compounds exhibited SARS-CoV-2 Mpro inhibition with IC50 values ranging 22.95–64.63 μM. These hit compounds exhibited good structural diversity, which prompted us to investigate their SARS-CoV-2 Mpro binding modes. We used a previously validated IFD-BPMD-MD workflow to predict the binding positions of these hit compounds. Our simulations showed that these hit complexes exhibited diverse and robust binding to the SARS-CoV-2 Mpro. Our study findings offer valuable insights into the development of novel noncovalent small-molecule protease inhibitor.

To ensure the safety of life and property of residents on landslides and reveal the deformation and failure law of masonry buildings on landslides, it is necessary to carry out a simulation study on the deformation and failure process of masonry buildings under the action of landslide deformation. A refined model of a masonry building was established based on the contact separation modeling method in ABAQUS, and the viscous contact interface was used to simulate the effect of mortar in the wall. Comparing the results of the numerical simulation with the physical model test results, the main conclusion is as follows: through the comparison of macroscopic deformation characteristics and microscopic stress and strain data obtained from physical and numerical model tests, the load-strain curve of the numerical model test agrees well with that of the physical model test, and their strain clouds are consistent, proving the validity of the numerical simulation method. The law of crack propagation and strain distribution of building walls in landslide tension areas is revealed, which can provide a basis for the protection design of masonry buildings in landslide tension areas.

Abstract Severe sleep deprivation (SD) has been highly associated with systemic energy wasting, such as lipid loss and glycogen depletion. Despite immune dysregulation and neurotoxicity observed in SD animals, whether and how the gut-secreted hormones participate in SD-induced disruption of energy homeostasis remains largely unknown. Using Drosophila as a conserved model organism, we characterize that production of intestinal Allatostatin A (AstA), a major gut-peptide hormone, is robustly increased in adult flies bearing severe SD. Interestingly, the removal of AstA production in the gut using specific drivers significantly improves lipid loss and glycogen depletion in SD flies without affecting sleep homeostasis. We reveal the molecular mechanisms whereby gut AstA promotes the release of an adipokinetic hormone (Akh), an insulin counter-regulatory hormone functionally equivalent to mammalian glucagon, to mobilize systemic energy reserves by remotely targeting its receptor AstA-R2 in Akh-producing cells. Similar regulation of glucagon secretion and energy wasting by AstA/galanin is also observed in SD mice. Further, integrating single-cell RNA sequencing and genetic validation, we uncover that severe SD results in ROS accumulation in the gut to augment AstA production via TrpA1. Altogether, our results demonstrate the essential roles of the gut-peptide hormone AstA in mediating SD-associated energy wasting.

Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy. Isocitrate dehydrogenases (IDHs) are a class of key proteins in energy metabolism, including IDH1, IDH2, and IDH3, which are involved in the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG). Mutants of IDH1 or IDH2 can produce d-2-hydroxyglutarate (D-2HG) with α-KG as the substrate, and then mediate the occurrence and development of cancer. At present, no IDH3 mutation has been reported. The results of pan-cancer research showed that IDH1 has a higher mutation frequency and involves more cancer types than IDH2, implying IDH1 as a promising anti-cancer target. Therefore, in this review, we summarized the regulatory mechanisms of IDH1 on cancer from four aspects: metabolic reprogramming, epigenetics, immune microenvironment, and phenotypic changes, which will provide guidance for the understanding of IDH1 and exploring leading-edge targeted treatment strategies. In addition, we also reviewed available IDH1 inhibitors so far. The detailed clinical trial results and diverse structures of preclinical candidates illustrated here will provide a deep insight into the research for the treatment of IDH1-related cancers.

Abstract Aim The aim of this study was to explore the experience and perceptions of patients with Crohn’s disease in China. Methods Data mining was used to investigate posts in Crohn’s disease online medical communities. The data were collected through the crawler code, and latent Dirichlet allocation (LDA) and grounded theory were used to mine the theme features after data cleaning. Results In analyzing the topic characteristics of online posts, LDA divided 6757 posts into 15 topics on four aspects: seeking disease information, making decisions on medication use, psychological burden, and communicating about diet and nutrition. Conclusion Overall, social media is patient-centric and helps us better understand the experiences and perceptions of patients. This study can help medical staff predict the thoughts and concerns of Crohn's disease patients during the treatment process, facilitate doctor-patient communication, and assist in the formulation of medical policies.

Abstract Aim The aim of the study was to develop an evidence‐based care bundle protocol for preventing falls in hospitalized children. Design Delphi method. Methods Based on the four basic concepts of nursing, the theoretical dimension and item pool of the care bundle first draft were constructed by searching evidence and referring to the care bundle for preventing inpatient fall issues by the China Nursing Quality Promotion Alliance. The Delphi method and trial tests were used to select and adjust items of the care bundle to form the care bundle protocol for preventing falls in hospitalized children. Results The first draft care bundle for preventing falls in hospitalized children included 4 dimensions and 21 items. In the 2‐round Delphi study, one item was removed, and three items were adjusted. One item was adjusted by trial test. Finally, the care bundle protocol for preventing falls in hospitalized children consisted of 4 dimensions and 20 items.

Objective(s): Patient-derived xenograft (PDX) model becomes a more and more important tool for tumor research. This study aimed to establish a colorectal cancer PDX model and verify its applicability.Materials and Methods: Fresh human colorectal cancer tissue was surgically removed and subcutaneously inoculated into immunodeficient mice to establish the PDX model. Hematoxylin and eosin (HE) staining and immunohistochemical staining were used to evaluate the model. The successful PDX model was selected to study the efficacy of capecitabine in treating colorectal cancer. Results: HE staining showed that the PDX mice model of colorectal cancer could preserve the histological characteristics of the primary tumor. Immunohistochemistry staining showed α-fetoprotein (AFP), carcinoembryonic antigen (CEA), and E-cadherin were strongly positively expressed in primary human and PDX tumor tissues, with a high degree of similarity. Capecitabine significantly inhibited PDX tumor growth and reduced the expression of AFP and CEA proteins in the tumor tissues (all Ps

In this article, quality rapid determination of cherry fruit (Prunus spp.) using artificial olfactory technique (AOT) combined with non-linear data extraction model was studied. AOT system was developed and used for cherry quality detection. AOT system responses to cherry samples stored at 4°C were recorded. At the same time, physical/chemical indexes, such as human sensory evaluation (HSE), firmness, color, pH, total soluble solids (TSS), and reducing sugar content (RSC), were examined to provide quality references to the cherry samples. AOT data was analyzed by principal component analysis (PCA), and bilayer stochastic resonance (BSR) models. PCA only partially discriminated the cherry samples. The signal-to-noise ratio (SNR) maximum values (SNR-Max) generated by BSR successfully discriminated all the samples. Multiple variable regression (MVR) between cherry physical/chemical indexes and BSR SNR-Max values was conducted. Results indicated that BSR was suitable for cherry quality rapid evaluation. Cherry quality examination model was built based on linear fitting regression on BSR eigen values. Validation tests results indicated that the developed model has good forecasting accuracy. The proposed method had some advantages, such as rapid responses, high accuracy, easy operation, etc.

Abstract Study design A combined retrospective and prospective analysis on the therapeutic effect of physiotherapeutic scoliosis-specific exercise (PSSE) in mild juvenile idiopathic scoliosis (JIS) patients. Background At present, patients with mild JIS are generally treated by observation without any interventional treatment. This study analyzed the effects of PSSE on mild JIS, which provided a new approach for the treatment of JIS. Method A total of 52 patients with mild JIS (Cobb angle 10–19°), aged 4–9 years, self-selected into an observation group and a PSSE group. Patients performed the corrective posture exercises daily based on the Scientific Exercise Approach to Scoliosis (SEAS) to the best of their ability, and performed the over-corrective training based on Schroth methods for 30 min each day. Before and one year after the treatment, the Cobb angle and the angle of trunk rotation (ATR) were evaluated, and the results were compared between the two groups. Results After one year of treatment, the Cobb angle in the PSSE group decreased from 15.0(11.0–17.0)° to 5.0(2.0–12.0)°(p ≤ 0.001), while the Cobb angle in the observation group increased from 13.5(11.0–17.3)° to 16.0(10.8–20.0)° (p = 0.010). The ATR in the PSSE group decreased from 5.0(2.0–7.0)° to 3.0(2.0–4.0)° (p = 0.009), while the change of ATR in the observation group was not significant. Compared with the observation group, 69.57% of patients in PSSE group had a decreased Cobb angle of more than 5 degrees, which was statistically significant(p ≤ 0.001). Conclusion For mild JIS, PSSE decreased the Cobb angle and ATR.

Abstract Background In recent years, an increasing number of studies have indicated that circular RNA plays crucial roles in regulating tumor development and chemoresistance. Using two high-throughput RNA sequence datasets, we previously found that circEXOC6B was downregulated in colon cancer. However, its role and mechanism in colorectal cancer (CRC) remained unknown. Methods Real-time quantitative PCR was used to examine the expression of circEXOC6B in CRC tissues. In vivo and in vitro functional experiments were performed to determine the suppressor role of circEXOC6B in CRC progression. RNA pull-down, mass spectrometry, RNA-binding protein immunoprecipitation, co-immunoprecipitation, fluorescence in situ hybridization, and immunofluorescence were applied to investigate the possible mechanisms connecting circEXOC6B to CRC growth and 5-fluorouracil-induced apoptosis. Chromatin immunoprecipitation, dual-luciferase assay, western blot, and immunohistochemistry were used to explore the mechanisms underlying the HIF1A regulation of RRAGB transcription. Results circEXOC6B was downregulated in CRC tissues, and its lower expression was associated with poor prognosis of patients. Functional experiments showed that circEXOC6B inhibited growth and increased the 5-fluorouracil-induced apoptosis of CRC cells in vitro and in vivo. Mechanistically, circEXOC6B inhibited the heterodimer formation of RRAGB by binding to it, thereby suppressing the mTORC1 pathway and HIF1A level. In addition, HIF1A upregulated the transcription of RRAGB by binding to its promoter region. Altogether, the results demonstrated that a HIF1A-RRAGB-mTORC1 positive feedback loop drives tumor progression in CRC, which could be interrupted by circEXOC6B. Conclusions circEXOC6B inhibits the progression of CRC and enhances the chemosensitivity of CRC cells to 5-fluorouracil by antagonizing the HIF1A-RRAGB-mTORC1 positive feedback loop. circEXOC6B is a possible therapeutic target for CRC treatment.

In our ongoing work on the identification of potent anti-inflammatory agents, we designed and synthesized three series of lathyrane diterpenoid hybrids in which the lathyrane diterpenoid skeleton was hybridized with other anti-inflammatory pharmacophores. Unexpectedly, lathyrane diterpenoid/3-hydroxyflavone hybrids showed more potent anti-inflammatory activity in RAW264.7 cells than did the corresponding parent compounds. Compound 8d1 exhibited potent anti-inflammatory activity with low cytotoxicity (IC50 = 1.55 ± 0.68 μM), and downregulated LPS-induced expression of iNOS and COX-2, as well as IκBα phosphorylation. This compound also inhibited the expression and nuclear translocation of NF-κB, and stimulated autophagy induction. Thus, 8d1’s anti-inflammatory mechanism is associated with inhibition of the NF-κB signaling pathway and increasing autophagy. This compound may serve as a promising anti-inflammatory agent.

BackgroundParkinson's disease is the second most common neurodegenerative disease in the world. However, current diagnostic methods are still limited, and available treatments can only mitigate the symptoms of the disease, not reverse it at the root. The immune function has been identified as playing a role in PD, but the exact mechanism is unknown. This study aimed to search for potential immune-related hub genes in Parkinson's disease, find relevant immune infiltration patterns, and develop a categorical diagnostic model.MethodsWe downloaded the GSE8397 dataset from the GEO database, which contains gene expression microarray data for 15 healthy human SN samples and 24 PD patient SN samples. Screening for PD-related DEGs using WGCNA and differential expression analysis. These PD-related DEGs were analyzed for GO and KEGG enrichment. Subsequently, hub genes (dld, dlk1, iars and ttd19) were screened by LASSO and mSVM-RFE machine learning algorithms. We used the ssGSEA algorithm to calculate and evaluate the differences in nigrostriatal immune cell types in the GSE8397 dataset. The association between dld, dlk1, iars and ttc19 and 28 immune cells was investigated. Using the GSEA and GSVA algorithms, we analyzed the biological functions associated with immune-related hub genes. Establishment of a ceRNA regulatory network for immune-related hub genes. Finally, a logistic regression model was used to develop a PD classification diagnostic model, and the accuracy of the model was verified in three independent data sets. The three independent datasets are GES49036 (containing 8 healthy human nigrostriatal tissue samples and 15 PD patient nigrostriatal tissue samples), GSE20292 (containing 18 healthy human nigrostriatal tissue samples and 11 PD patient nigrostriatal tissue samples) and GSE7621 (containing 9 healthy human nigrostriatal tissue samples and 16 PD patient nigrostriatal tissue samples).ResultsUltimately, we screened for four immune-related Parkinson's disease hub genes. Among them, the AUC values of dlk1, dld and ttc19 in GSE8397 and three other independent external datasets were all greater than 0.7, indicating that these three genes have a certain level of accuracy. The iars gene had an AUC value greater than 0.7 in GES8397 and one independent external data while the AUC values in the other two independent external data sets ranged between 0.5 and 0.7. These results suggest that iars also has some research value. We successfully constructed a categorical diagnostic model based on these four immune-related Parkinson's disease hub genes, and the AUC values of the joint diagnostic model were greater than 0.9 in both GSE8397 and three independent external datasets. These results indicate that the categorical diagnostic model has a good ability to distinguish between healthy individuals and Parkinson's disease patients. In addition, ceRNA networks reveal complex regulatory relationships based on immune-related hub genes.ConclusionIn this study, four immune-related PD hub genes (dld, dlk1, iars and ttd19) were obtained. A reliable diagnostic model for PD classification was developed. This study provides algorithmic-level support to explore the immune-related mechanisms of PD and the prediction of immune-related drug targets.

The Oriental Stork (Ciconia boyciana) is listed as ‘Endangered’ on the International Union for the Conservation of Nature (IUCN) Red List of Threatened Species and is classified as a first category nationally protected bird species in China. Understanding this species' seasonal movements and migration will facilitate effective conservation to promote its population. We tagged 27 Oriental Stork nestlings at Xingkai Lake on the Sanjiang Plain in Heilongjiang Province, China, used GPS tracking to follow them over the periods of 2014–2017 and 2019–2022, and confirmed their detailed migratory routes using the spatial analysis function of ArcGIS 10.7. We discovered four migration routes during autumn migration: one common long-distance migration route in which the storks migrated along the coastline of Bohai Bay to the middle and lower reaches of the Yangtze River for wintering, one short-distance migration route in which the storks wintered in Bohai Bay and two other migration routes in which the storks crossed the Bohai Strait around the Yellow River and wintered in South Korea. There were no significant differences in the number of migration days, residence days, migration distances, number of stopovers and average number of days spent at stopover sites between the autumn and spring migrations (P > 0.05). However, the storks migrated significantly faster in spring than in autumn (P ​= ​0.03). The same individuals did not exhibit a high degree of repetition in their migration timing and route selection in either autumn or spring migration. Even storks from the same nest exhibited considerable between-individual variation in their migration routes. Some important stopover sites were identified, especially in the Bohai Rim Region and on the Songnen Plain, and we further explored the current conservation status at these two important sites. Overall, our results contribute to the understanding of the annual migration, dispersal and protection status of the endangered Oriental Stork and provide a scientific basis for conservation decisions and the development of action plans for this species.

Background Evidence indicates that medical students have had high rates of mental health problems, especially during the COVID-19 pandemic, which could be affected by alexithymia—a marked dysfunction in emotional awareness, social attachment and interpersonal relationships—and stress. However, psychological resilience might relieve alexithymia and stress levels.Aims This study aimed to investigate the role of resilience in alexithymia and stress in medical students.Methods A total of 470 medical students completed online and offline surveys, including the Toronto Alexithymia Scale-20 (TAS-20), the Connor-Davidson Resilience Scale (CD-RISC) and the College Student Stress Questionnaire (CSSQ). The data of five participants were excluded because of a lack of integrity. Mann-Whitney U test or Kruskal-Wallis test was used to compare group differences in the CD-RISC scores among categorical variables. Spearman correlation analysis was employed to evaluate the associations between resilience and alexithymia and between resilience and stress. Mediation analysis was used to test the mediating effect of resilience between alexithymia and stress.Results Of the medical students considered in the analysis, 382 (81.28%) were female and 88 (18.72%) were male. There was a significant negative correlation between the TAS-20 scores and the total and subtotal CD-RISC scores (p

BackgroundAs one of the most common malignant tumor, colorectal cancer (CRC) continues to have a high incidence and mortality rate. HRK belongs to the BCL-2 protein family, which has been shown to have antitumor effects in prostate cancer. However, its role in colorectal cancer is not yet known.MethodsIn this study, we verified the expression levels of HRK in colorectal cancer tissues by public database search as well as immunohistochemistry. Next, we analyzed HRK expression levels in CRC tissues,adjacent non-cancerous tissues, cell lines and normal intestinal epithelial cells by qPCR and Western blotting. CCK-8 proliferation assays, transwell assays, wound healing assays, colony assays and flow cytometry were performed to clarified the effect of HRK on CRC cells. Western blotting and rescue experiments were used to determine the role of HRK in regulating PI3K/AKT/mTOR signaling pathway.ResultsHRK expression was lower in CRC tissues and cell lines. Gain and loss of function experiments showed that HRK decreased proliferation, invasion and migration of CRC cells. Low expression of HRK inhibited CRC cell apoptosis as well as activated the PI3K/AKT/mTOR signaling pathway. In addition, rapamycin inhibits the activation of PI3K/AKT/mTOR signaling pathway and reverses HRK-induced alterations in cell biological functions.ConclusionOur study demonstrates that HRK is lowly expressed in colorectal cancer tissues. And for the first time, HRK was shown to promote apoptosis and inhibit proliferation of colorectal cancer cells by inhibiting PI3K/AKT/mTOR signaling pathway. HRK represents a potential target for the treatment of CRC.

Hehui capsule (Hhc) has been used as an assistant treatment for hyperlipidemia. According to the previous studies, miltiorrhiza and Chavica roxburghii may reduce the serum lipid level. This study aims at examining the efficiency of Hehui capsule with regards to treating hyperlipidemia in a randomized control, double-blind clinical trial. In the research, we assigned 104 eligible subjects to Hehui capsule group and placebo groups (52:52, respectively). Subjects used self-control and inter-group controls to compare serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL) and other changes before and after the test group and the test group and the control group. During the 45 days intervention, 101 cases were actually included, among which 51 cases for test group, and other 50 cases for placebo group. The total effective rate of blood lipid reduction (90.20%) in the test group was significantly higher than that in the control group (26.00%) (P ​

The 2020 COVID-19 lockdown provides an opportunity to assess how the anthropause affected the behavior of birds. Black-headed gulls (Larus ridibundus) wintering at Dianchi Lake (Yunnan Province, southwestern China) prefer to forage on easily accessible human-provided food at various sites along the lake. Following the closure of the lake because of the pandemic, synthetic food was provided at a single location. We expected that the home range size and distribution of gulls would change in response to these changes in food provisioning. A total of 91 gulls were tagged with satellite transmitters in November 2018 and March 2019, and their movements were tracked during the winter months. We analyzed their home range size and spatial distribution in four periods, SCP2019, SOP2019, SCP2020, and SOP2020 (Scenic Opening/Closing Period in 2019/2020), and the difference between SOP2019 and SCP2019 was used as the control group. The eutrophication level in the wintering periods “Nov. 2018–Apr. 2019” and “Oct. 2019–Apr. 2020” was determined using the Normalized Difference Vegetation Index (NDVI), and the coverage ratio of algal blooms and NDVI were used as indicators of the amount of naturally available food. The home range sizes of gulls were reduced in SCP2020 compared with SOP2019, SCP2019, and SOP2020. The gulls were most abundant in the 600–900 m buffer zone and least abundant in the 0–300 m buffer zone in SCP2019; they were most abundant in the 0–300 m buffer zone and least abundant in the 900–2000 m buffer zone in SCP2020. These patterns were consistent with variation in the NDVI and the coverage ratio of algal blooms among buffer zones. Changes in wintering behaviors in SCP2020 relative to other periods suggested that gulls modified their behavior following anthropause-related changes in the distribution and provisioning of food. Our findings provide insights into the role of behavioral plasticity in mediating adaptation to changes in human activities in birds.

The topspin forehand is the most frequent and effective shot in top-level table tennis matches. The present study assesses the biomechanical differences in the topspin forehand stroke technique when the incoming ball is in different rotations. Eight national level-1 male table tennis athletes (176.6 ± 4.8 cm, 70.8 ± 6.6 kg, 20.9 ± 2.4 yr) performed two kinds of techniques—topspin forehand strokes against topspin (AT) and against backspin (AB) balls, respectively. The kinematic parameters of their bodies and rackets were calculated. Meanwhile, the force plates analyzed their lower limb moments through inverse dynamics. Paired t-test and non-parametric paired t-test mapping were used to assess the differences between the two conditions. Their center of gravity (COG) vertical distance, elbow flexion, thorax–pelvis flexion, and knee flexion angles had significant differences during the stroke phase (p < 0.05). The moment of the racket-side hip rotation and ankle dorsiflexion showed significant differences during the stroke phase (p < 0.05). The racket velocity, angle, and trajectories showed significant differences at characteristic moments (p < 0.05). This study revealed the different topspin forehand stroke techniques in table tennis, even though the two movements look similar. Compared with AT strokes, the athletes kept a straight elbow and lower center of gravity than they did during the stroke phase of AB strokes. They increased the distance of the racket trajectory and velocity to meet the incoming ball with a backspin, especially in the vertical direction. This detailed information is necessary for beginners to improve the efficiency of their forehand topspin technique, especially in strokes against incoming balls with different rotations.

Clinical practice shows that when single-target drugs treat multi-factor diseases such as tumors, cardiovascular system and endocrine system diseases, it is often difficult to achieve good therapeutic effects, and even serious adverse reactions may occur. Multi-target drugs can simultaneously regulate multiple links of disease, improve efficacy, reduce adverse reactions, and improve drug resistance. They are ideal drugs for treating complex diseases, and therefore have become the main direction of drug development. At present, some multi-target drugs have been successfully used in many major diseases. Entrectinib is an oral small molecule inhibitor that targets TRK, ROS1, and ALK. It is used to treat locally advanced or metastatic solid tumors with NTRK1/2/3, ROS1 and ALK gene fusion mutations. It can pass through the blood-brain barrier and is the only TRK inhibitor clinically proven to be effective against primary and metastatic brain diseases. In 2019, entrectinib was approved by the FDA to treat adult patients with ROS1-positive metastatic non-small cell lung cancer. Case reports showed that continuous administration of entrectinib was effective and tolerable. In this review, we give a brief introduction to TKK, ROS1 and ALK, and on this basis, we give a detailed and comprehensive introduction to the mechanism of action, pharmacokinetics, pharmacodynamics, clinical efficacy, tolerability and drug interactions of entrectinib.

Perfluorooctanoic acid (PFOA) represents an increasing public health concern due to its persistence in the environment and its toxic effects. The gut microbiota is known to produce various metabolites that assist the host to maintain metabolic homeostasis. However, few studies have explored the effects of PFOA on gut-microbiota-related metabolites. In the present study, male C57BL/6J mice were exposed to 1 ppm of PFOA in drinking water for four weeks and integrative analysis of the gut microbiome and metabolome was performed to reveal the health effects of PFOA. Our results showed that PFOA disturbed both the gut microbiota composition and the metabolic profiles of the feces, serum, and liver in mice. A correlation was found between Lachnospiraceae UCG004, Turicibacter, Ruminococcaceae, and different fecal metabolites. Significant alterations of gut-microbiota-related metabolites were induced by PFOA exposure, including bile acids and tryptophan metabolites such as 3-indoleacrylic acid and 3-indoleacetic acid. The findings of this study are helpful to improve the understanding of the health effects of PFOA, which might be mediated through the gut microbiota and its related metabolites.

Triploid rainbow trout can adapt to various dietary lipid levels; however, the mechanisms of systematic adaptation are not well understood. To investigate how adult triploid rainbow trout maintains lipid hemostasis under different exogenous lipid intake, a 77-day feeding trial was conducted. Diets with lipid contents of 20%, 25%, and 30% were formulated and fed to triploid rainbow trout with an initial weight of 3 ± 0.02 kg, and they were named L20, L25, and L30 group, respectively. Results showed that the condition factor, hepatosomatic index, liver color, and plasma triglyceride were comparable among three groups (p > 0.05), whereas the value of specific growth rate, viscerosomatic index, and liver glycogen content gradually increased with increasing dietary lipid level (p < 0.05). A significantly highest value of plasma glucose and nonesterified fatty acids were found in the L30 group (p < 0.05), whereas the significantly higher content of plasma total cholesterol, high-density lipoprotein–cholesterol, and low-density lipoprotein–cholesterol was found in the L25 group compared with those in L20 group (p < 0.05). As for lipid deposition, abdominal adipose tissue, and muscle were the main lipid storage place for triploid rainbow trout when tissues’ weight is taken into consideration. Overall quantitative PCR showed that the lipid transport and glycolysis were upregulated, and fatty acids oxidative was downregulated in liver when fish were fed low lipid diets. It meant that the liver was the primary lipid metabolizing organ to low lipid diet feeding, which could switch energy supply between glycolysis and fatty acids oxidation. Fish fed with a moderate dietary lipid level diet could increase lipid uptake and promote lipogenesis in muscle. Abdominal adipose tissue could efficiently uptake excess exogenous free fatty acid through upregulating fatty acid uptake and synthesis de novo and then storing it in the form of triglyceride. Excess lipid uptake is preferentially stored in abdominal adipose tissue through coordinated fatty acid uptake and fatty acid synthesis de novo as dietary lipid levels increased. In summary, triploid rainbow trout can adapt to various dietary lipid levels by coordinating metabolism in different tissues.