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Wang Tang1 *, Zhen-Wei Li1 *, Gui-Qiang Miao2 *, Zhi-Peng Li,1 Tao Gui,1 Chong-Jie Wu,1 Zhen-Yan Li,1 Jie Yang,1 Xiao-Dong Zhao,2 Ning Liu,1 Zhen-Gang Zha,1 Lu-Tian Yao,3 Huan-Tian Zhang1 1Department of Bone and Joint Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China; 2Department of Orthopedics, Foshan Fosun Chancheng Hospital, Foshan, 528010, People’s Republic of China; 3Department of Orthopedics, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lu-Tian Yao; Huan-Tian Zhang, Email ltyao@cmu.edu.cn; zhanghuantian@jnu.edu.cnPurpose: Subchondral insufficiency fracture of the knee (SIFK) is a common cause of knee joint pain that mainly afflicts the elderly. Until now, how a sudden insufficiency fracture of subchondral bone affects the transcriptomic profiles of cartilage in SIFK and OA patients are largely unknown.Methods: Single-cell RNA sequencing (scRNA-seq) was used to identify various cell subsets and evaluate transcriptomic differences in cartilage of SIFK and OA patients. In addition, the above findings were confirmed by histological evaluation and immunohistochemical (IHC) staining.Results: We found that the transcriptomic profiles of cartilage in the SIFK patient was completely different from those of normal and OA patients. Accordingly, several novel cell clusters with activation of hypoxia and endochondral ossification signaling were identified in the SIFK cartilage. Chondrocyte trajectories analysis and IHC staining revealed that transcription factors including TCF4 were found to be highly up-regulated during the occurrence of SIFK, which might drive the reactive formation of cartilage and fibrous tissue and the activation of endochondral ossification.Conclusion: This is the first report to elucidate the transcriptomic alterations and distinct cell type subpopulations in the cartilage of SIFK and OA by the use of scRNA-seq, which provides a new insight in the understanding of the initiation and progression of SIFK.Keywords: SIFK, scRNA, TCF4, cartilage, hypoxia

Li-juan Zheng,1 Jia-chi Ma,2 Dong Fang,3 Li-gang Wu,4 Zhen-qiang Gong,4 Jian-bo Qi,5 Xiao-dan Zhao,4 Jian-bo Du,4 Pei-lan Ma5 1Department of Gastroenterology, Gansu Province People’s Hospital, Lanzhou, People’s Republic of China; 2Department of General Surgery, Gansu Province People’s Hospital, Lanzhou, People’s Republic of China; 3Department of Vascular Surgery, Gansu Province People’s Hospital, Lanzhou, People’s Republic of China; 4Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 5Gansu University of Traditional Chinese Medicine, Lanzhou, People’s Republic of China Background: This study aimed to analyze the stage-situation depression and anxiety as well as independent influential factors in patients with postsurgical gastroparesis syndrome (PGS)and to provide dependent indications for treatment. Patients and methods: The self-rating depression scale (SDS) and self-rating anxiety scale (SAS) were used to test the depression and anxiety of 53 patients with PGS, who were treated in the Department of Gastroenterological Surgery of Gansu Provincial Hospital from January 2012 to October 2016. A comparison between the SDS or SAS scores of patients with PGS and without PGS was undertaken; then, we retrospectively analyzed the factors influencing depression and anxiety in PGS patients. Results: The patients with PGS’ mean scores of depression and anxiety were 49.92±11.37 and 50.91±6.57, respectively, which were higher than that of patients without PGS in the Chinese population (P

Yan-Gang Qu,1 Qian Zhang,2 Qi Pan,3 Xian-Da Zhao,4 Yan-Hua Huang,2 Fu-Chun Chen,3 Hong-Lei Chen41Department of Pathology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, 2Department of Molecular Pathology, Wuhan Nano Tumor Diagnosis Engineering Research Center, Wuhan, Hubei, People’s Republic of China; 3Department of Thoracosurgery, Traditional Chinese Medical Hospital of Wenling, Wenling, Zhejiang, People’s Republic of China; 4Department of Pathology, School of Basic Medical Science, Wuhan University, Wuhan, Hubei, People’s Republic of ChinaBackground: Epidermal growth factor receptor (EGFR) mutation status plays an important role in therapeutic decision making for non-small cell lung cancer (NSCLC) patients. Since EGFR mutation-specific antibodies (E746-A750del and L858R) have been developed, EGFR mutation detection by immunohistochemistry (IHC) is a suitable screening test. On this basis, we want to establish a new screening test, quantum dots immunofluorescence histochemistry (QDs-IHC), to assess EGFR gene mutation in NSCLC tissues, and we compared it to traditional IHC and amplification refractory mutation system (ARMS).Materials and methods: EGFR gene mutations were detected by QDs-IHC, IHC, and ADx-ARMS in 65 cases of NSCLC composed of 55 formalin-fixed, paraffin-embedded specimens and ten pleural effusion cell blocks, including 13 squamous cell carcinomas, two adenosquamous carcinomas, and 50 adenocarcinomas.Results: Positive rates of EGFR gene mutations detected by QDs-IHC, IHC, and ADx-ARMS were 40.0%, 36.9%, and 46.2%, respectively, in 65 cases of NSCLC patients. The sensitivity of QDs-IHC when detecting EGFR mutations, as compared to ADx-ARMS, was 86.7% (26/30); the specificity for both antibodies was 100.0% (26/26). IHC sensitivity was 80.0% (24/30) and the specificity was 92.31% (24/26). When detecting EGFR mutations, QDs-IHC and ADx-ARMS had perfect consistency (κ=0.882; P

Non-steroidal anti-inflammatory drugs (NSAIDs) are effective for relieving pain but undesirable side effects limit their clinical usefulness. Choline is a [alpha]7 nicotinic receptor agonist that has antinociceptive effects in a variety of pain models. Drug combination is a strategy in the management of pain to reduce side effects. The aim of the study was to evaluate the nature of the interaction between choline and aspirin in two distinct inflammatory pain models. The analgesic mechanism of choline was also investigated. In the writhing test, intravenous administration of choline or aspirin showed dose-dependent antinociceptive activity, and isobolographic analysis revealed a synergistic nature of the interaction between choline and aspirin. More importantly, coadministration choline with aspirin could significantly shorten the antinociceptive latency of aspirin and prolong the antinociceptive duration of aspirin in the writhing test. In the carrageenan test, single administration of choline or aspirin significantly attenuated carrageenan-induced thermal hyperalgesia in a dose-dependent relationship. Coadministration of non-analgesic doses of aspirin with choline significantly suppressed the thermal hyperalgesia, with a longer duration efficacy. Furthmore, we found that [alpha]7 nicotinic, muscarinic, and opioid-receptors are involved in the antinociceptive effect of choline in the writhing test and the antinociceptive effect produced by systemically administered choline may be via a peripheral mechanism. In conclusion, coadministration of choline and aspirin holds promise for development as a safe analgesic drug combination for inflammatory pain, with a higher potency and longer duration than either aspirin or choline alone. [ABSTRACT FROM AUTHOR]

Background: Arsenic (As) metabolism pathways and their coupling to nitrogen (N) and carbon (C) cycling contribute to elemental biogeochemical cycling. However, how whole-microbial communities respond to As stress and which taxa are the predominant As-transforming bacteria or archaea in situ remains unclear. Hence, by constructing and applying ROCker profiles to precisely detect and quantify As oxidation (aioA, arxA) and reduction (arrA, arsC1, arsC2) genes in short-read metagenomic and metatranscriptomic datasets, we investigated the dominant microbial communities involved in arsenite (As(III)) oxidation and arsenate (As(V)) reduction and revealed their potential pathways for coupling As with N and C in situ in rice paddies., Results: Five ROCker models were constructed to quantify the abundance and transcriptional activity of short-read sequences encoding As oxidation (aioA and arxA) and reduction (arrA, arsC1, arsC2) genes in paddy soils. Our results revealed that the sub-communities carrying the aioA and arsC2 genes were predominantly responsible for As(III) oxidation and As(V) reduction, respectively. Moreover, a newly identified As(III) oxidation gene, arxA, was detected in genomes assigned to various phyla and showed significantly increased transcriptional activity with increasing soil pH, indicating its important role in As(III) oxidation in alkaline soils. The significant correlation of the transcriptional activities of aioA with the narG and nirK denitrification genes, of arxA with the napA and nirS denitrification genes and of arrA/arsC2 with the pmoA and mcrA genes implied the coupling of As(III) oxidation with denitrification and As(V) reduction with methane oxidation. Various microbial taxa including Burkholderiales, Desulfatiglandales, and Hyphomicrobiales (formerly Rhizobiales) are involved in the coupling of As with N and C metabolism processes. Moreover, these correlated As and N/C genes often co-occur in the same genome and exhibit greater transcriptional activity in paddy soils with As contamination than in those without contamination., Conclusions: Our results revealed the comprehensive detection and typing of short-read sequences associated with As oxidation and reduction genes via custom-built ROCker models, and shed light on the various microbial taxa involved in the coupling of As and N and C metabolism in situ in paddy soils. The contribution of the arxA sub-communities to the coupling of As(III) oxidation with nitrate reduction and the arsC sub-communities to the coupling of As(V) reduction with methane oxidation expands our knowledge of the interrelationships among As, N, and C cycling in paddy soils. Video Abstract., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

This article presents a new event-triggered adaptive finite-time control strategy using a fuzzy state observer for a class of nonlinear cyber-physical systems (CPSs) under malicious deception attacks with a more general form. Compared with the traditional assumptions on the deception attacks in the existing results, a more general assumption on deception attacks is given in this article. During the design process, real system states are initially estimated by developing an improved state observer, which effectively addresses the problem of state unavailability. Then, a coordinate transformation technology, in which the estimated states of observer are considered, is presented to stabilize the studied system. By constructing the singularity-free finite time virtual controls, the singularity problem in the traditional finite time design algorithms is cleverly avoided. Furthermore, to minimize communication overhead, a final finite-time controller is established by using a relative threshold event-triggered scheme. The developed event-triggered adaptive finite-time control strategy guarantees that all signals in the closed-loop system are semi-globally bounded in finite time without Zeno behavior. Finally, the correctness of the proposed control strategy is validated through two simulation results.

Loss of ARID1A has been reported to drive the progression of lung adenocarcinoma, yet the underlying mechanism remains elusive. In this study, we performed secretome analysis to identify the key secreted proteins regulating lung adenocarcinoma progression. We showed that the VASN level was significantly elevated in the conditioned medium from ARID1A-depleted A549 and H1299 cells. Restoration of ARID1A in ARID1A-depleted lung adenocarcinoma cells prevented the upregulation and secretion of VASN. Clinical analysis demonstrated a negative correlation between ARID1A and VASN expression in ARID1A-mutated lung adenocarcinomas. The patients with ARID1A-mutated lung adenocarcinoma had significantly higher concentrations of serum VASN than healthy controls. Moreover, serum VASN concentrations were associated with TNM stage, lymph node metastasis, and overall survival of the patients with ARID1A-mutated lung adenocarcinoma. Functional studies indicated that VASN overexpression potentiated the proliferation, invasion, and tumorigenesis of lung adenocarcinoma cells. Antibody neutralization of VASN suppressed the aggressiveness of ARID1A-depleted lung adenocarcinoma cells both in vitro and in vivo. Addition of recombinant VASN protein promoted the proliferation and invasion of lung adenocarcinoma cells. Additionally, knockdown of Notch1 blocked the aggressive phenotype induced by recombinant VASN protein. In conclusion, our data uncover the role of VASN in mediating the progression of ARID1A-depleted lung adenocarcinoma and highlight VASN as a promising therapeutic target for this disease., (© 2024. The Author(s).)

Background: Glycated haemoglobin (HbA1c) is a well-established biomarker for diabetes diagnosis and management and is linked to risk of cardiovascular death. However, among adults without cardiovascular disease (CVD) and diabetes, the value of HbA1c in predicting distinct signatures of myocardial ageing has not been explored., Methods: Subjects, from among older adults without CVD, underwent comprehensive cardiovascular and metabolic assessment. Transthoracic echocardiography measured left ventricular structure and function. Longitudinal left atrial (LA) strain comprising reservoir strain (Ɛs), conduit strain (Ɛe) and booster strain (Ɛa) and their corresponding peak strain rates (SRs, SRe, SRa) were measured using cardiac magnetic resonance (CMR). Blood sampling for biomarkers and cardiovascular examinations were performed., Results: 247 subjects (mean age 71 years, 44.1% female, mean HbA1c 6.0%) were included. HbA1c was significantly associated with E/A ratio (p < 0.0001), conduit strain (Ɛe) (p < 0.0001), conduit strain rate SRe (p < 0.0001), and conduit strain rate to booster strain rate SRe:SRa ratio (p < 0.0001). Multivariate models adjusting for clinical variables such as body mass index, blood pressure, heart rate, diabetes mellitus, smoking, and associated cardiac parameters, demonstrated a persistent independent association. Each unit increase in HbA1c was associated with lower E/A ratio, lower Ɛe, higher SRe and lower SRe:SRa ratio. These associations remained significant after diabetic subjects were excluded., Conclusion: Distinct associations were found between HbA1c and myocardial functions of interest in the ageing heart. HbA1c may be useful biomarker for stratifying risks associated with myocardial ageing, independent of diabetes status., Trial Registration: ClinicalTrials.gov Identifier: NCT02791139., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

Arsenic (As) contamination and methane (CH 4 ) emissions co-occur in rice paddies. However, how As impacts CH 4 production, oxidation, and emission dynamics is unknown. Here, we investigated the abundances and activities of CH 4 -cycling microbes from 132 paddy soils with different As concentrations across continental China using metagenomics and the reverse transcription polymerase chain reaction. Our results revealed that As was a crucial factor affecting the abundance and distribution patterns of the mcrA gene, which is responsible for CH 4 production and anaerobic CH 4 oxidation. Laboratory incubation experiments showed that adding 30 mg kg -1 arsenate increased 13 CO 2 production by 10-fold, ultimately decreasing CH 4 emissions by 68.5%. The inhibition of CH 4 emissions by As was induced through three aspects: (1) the toxicity of As decreased the abundance and activity of the methanogens; (2) the adaptability and response of methanotrophs to As is beneficial for CH 4 oxidation under As stress; and (3) the more robust arsenate reduction would anaerobically consume more CH 4 in paddies. Additionally, significant positive correlations were observed between arsC and pmoA gene abundance in both the observational study and incubation experiment. These findings enhance our understanding of the mechanisms underlying the interactions between As and CH 4 cycling in soils.

Objective: The aim of this study was to conduct a systematic evaluation of exercise interventions' effectiveness on antenatal depressive symptoms in pregnant women and to investigate the impact of different intervention factors on the relationship between exercise and antenatal depressive symptoms., Methods: We conducted comprehensive searches in several databases, including PubMed, Embase, Web of Science, Cochrane Library, and others. The search period covered from database inception to May 2023. After thorough screening, a total of 7 papers with 524 subjects were included in the analysis., Results: The meta-analysis revealed that the overall effect size of exercise intervention on antenatal depressive symptoms in pregnant women was SMD = -0.41, with a 95% confidence interval of [-0.78, -0.05], and P = 0.03, indicating a significant improvement in depressive symptoms due to exercise intervention during the antenatal period. However, some degree of heterogeneity was observed among the studies, with I² = 74%, P = 0.0007., Conclusion: The results indicate that exercise interventions significantly contribute to the improvement of antenatal depressive symptoms in pregnant women, as inferred from the combined findings of the studies. Notably, static exercise intervention showed better results than dynamic exercise intervention. Moreover, interventions conducted before 20 weeks' gestation had superior outcomes compared to those conducted after 20 weeks' gestation, and interventions lasting longer than the trimester duration exhibited more favorable effects than shorter interventions. However, to validate these findings and optimise exercise intervention protocols for better antenatal maternal depressive symptom management, larger sample sizes and more comprehensive studies are required, given the observed heterogeneity and potential limitations in the present study., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/ PROSPERO, identifier (CRD42023422315)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Liu, Sun and Zhao.)

Objective: To investigate the long-term therapeutic effects and safety of renal denervation (RDN) on hypertensive patients with different cardiovascular risks, as well as its impact on adverse events, cardiovascular death and all-cause mortality. Methods: This was a single-center, single-arm, real-world retrospective study. Patients with refractory hypertension who underwent RDN at Tianjin First Central Hospital from July 6, 2011 to December 23, 2015 were enrolled and divided into either a high or intermediate-low risk group based on baseline cardiovascular risk. The treatment responsiveness of hypertensive patients with different cardiovascular stratification to RDN was assessed by comparing the results of office blood pressure, home blood pressure, and 24-h ambulatory blood pressure monitoring at 1, 5, and 11 years after RDN. Long-term safety of RDN was assessed by creatinine, and estimated glomerular filtration rate (eGFR) at 1 and 11 years after RDN. In addition, the total defined daily dose (DDD) of antihypertensive medications and the incidence of long-term adverse events, cardiovascular deaths, and all-cause deaths after RDN were followed up 11 years after RDN in person or by telephone. Results: A total of 62 patients with refractory hypertension, aged (50.2±15.0) years, of whom 35 (56.5%) were male, were included. There were 35 cases in high-risk group and 27 cases in low and medium risk group. The decrease in clinic systolic blood pressure (high risk vs. low-medium risk: (-38.0±15.1) mmHg vs. (-25.0±16.6) mmHg(1 mmHg=0.133kPa), P =0.002), home self-measured systolic blood pressure ((-28.4±12.7) mmHg vs. (-19.7±13.1) mmHg, P =0.011) and clinic systolic blood pressure 11 years after RDN ((-43.0±18.4) mmHg vs. (-27.8±17.9) mmHg, P =0.003) in the high-risk group was significantly higher than that in the low-medium risk group. The differences in heart rate and the decrease in total DDD number of antihypertensive drugs between the two groups were not statistically significant (all P >0.05). Creatinine and eGFR levels in the two groups at 1 and 11 years after RDN were not statistically significant when compared with the baseline values (all P >0.05). The cumulative cardiovascular mortality rate was 1.6% (1/62) and 8.1% (5/62), and the cumulative all-cause mortality rate was 3.2% (2/62) and 11.3% (7/62) at 5 and 11 years after RDN, respectively. The differences in the incidence rate of adverse events, cardiovascular mortality, and all-cause mortality rate between the two groups were not statistically significant (all P >0.05). Conclusions: RDN has long-term antihypertensive effect and good safety. Hypertensive patients who belong to the high-risk stratification of cardiovascular risk may respond better to RDN treatment.

Contactin-associated protein1 (Caspr1) plays an important role in the formation and stability of myelinated axons. In Caspr1 mutant mice, autophagy-related structures accumulate in neurons, causing axonal degeneration; however, the mechanism by which Caspr1 regulates autophagy remains unknown. To illustrate the mechanism of Caspr1 in autophagy process, we demonstrated that Caspr1 knockout in primary neurons from mice along with human cell lines, HEK-293 and HeLa, induced autophagy by downregulating the PI3K/AKT/mTOR signaling pathway to promote the conversion of microtubule-associated protein light chain 3 I (LC3-I) to LC3-II. In contrast, Caspr1 overexpression in cells contributed to the upregulation of this signaling pathway. We also demonstrated that Caspr1 knockout led to increased LC3-I protein expression in mice. In addition, Caspr1 could inhibit the expression of autophagy-related 4B cysteine peptidase (ATG4B) protein by directly binding to ATG4B in overexpressed Caspr1 cells. Intriguingly, we found an accumulation of ATG4B in the Golgi apparatuses of cells overexpressing Caspr1; therefore, we speculate that Caspr1 may restrict ATG4 secretion from the Golgi apparatus to the cytoplasm. Collectively, our results indicate that Caspr1 may regulate autophagy by modulating the PI3K/AKT/mTOR signaling pathway and the levels of ATG4 protein, both in vitro and in vivo. Thus, Caspr1 can be a potential therapeutic target in axonal damage and demyelinating diseases., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear., Aims of the Study: This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH., Materials and Methods: The study employed network pharmacology, UPLC-Q-TOF-MS technique, molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms., Results: Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression., Conclusion: Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The aim of this study is to report the risk factors of severe statin induced liver injury (SILI). From the database of Shandong ADR Monitoring Center and Outpatients and inpatients in our hospital, SILI cases reported from 2013 to 2021 were extracted and screened. The diagnostic criteria of SILI, the inclusion and exclusion criteria of severe and general SILI were established separately. After the SILI cases were selected and confirmed, the socio-demographic and clinical characteristics were collected. Single factor chi-square test and multi-factor unconditional logistic regression analysis were used to analyze the influencing factors of severe SILI. From 1391 reported cases, 1211 met SILI diagnostic criteria, of which 157 were severe SILI and 964 were general SILI. Univariate analysis showed that age, drug combination, statin category were the influencing factors of severe SILI (p<0.1). Multivariate logistic analysis showed that drug combination and statin category were the influencing factors of severe SILI (p<0.05). Atorvastatin caused the most serious SILI, and its risk is 1.77 times higher than rosuvastatin. The serious SILI risk of drug combination was 2.08 times higher than statin alone. The patient with these factors should be monitored intensively during clinical treatment, to ensure their medication safety., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: ELF4 deficiency has been recently recognized as a novel disorder within the spectrum of inborn errors of immunity (IEIs), specifically categorized as a "disease of immune dysregulation." Cases of this condition, reported by our team and others, are very limited worldwide. As such, our current knowledge of this new disease remains preliminary. This review aims to provide a brief overview of the clinical manifestations, pathogenesis, and treatment strategies for this novel IEI., Data Sources: A comprehensive review was conducted after an extensive literature search in the PubMed/Medline database and websites concerning transcriptional factor ELF4 and reports concerning patients with ELF4 deficiency. Our search strategy was "ELF4 OR ETS-related transcription factor Elf-4 OR EL4-like factor 4 OR myeloid Elf-1-like factor" as of the time of manuscript submission., Results: The current signature manifestations of ELF4 deficiency disorder are recurrent and prolonged oral ulcer, abdominal pain, and diarrhea in pediatric males. In some cases, immunodeficiency and autoimmunity can also be prominent. Targeted Sanger sequencing or whole exome sequencing can be used to detect variation in ELF4 gene. Western blotting for ELF4 expression of the patient's cells can confirm the pathogenic effect of the variant. To fully confirm the pathogenicity of the variant, further functional test is strongly advised. Glucocorticoid and biologics are the mainstream management of ELF4 deficiency disorder., Conclusions: Pediatric males presenting with recurring ulcerations in digestive tract epithelium with or without recurrent fever should be suspected of DEX. When atypical presentations are prominent, variations in ELF4 gene should be carefully evaluated functionally due to the complex nature of ELF4 function. Experience of treating DEX includes use of glucocorticoid and biologics and more precise treatment needs more patients to identify and further mechanistic study., (© 2024. Children's Hospital, Zhejiang University School of Medicine.)

In this article, two novel adaptive fault-tolerant control schemes for a class of nonlinear strict-feedback cyber-physical systems (CPSs) with deception attacks are presented. Deception attacks, such as false data-injection attacks, which destroy sensor networks, make the outputs and states of the CPSs unavailable. It is very difficult and challenging for a designer to achieve the tracking control under the circumstance of cyberattacks. To realize the tracking control for the studied CPSs, we propose a new coordinate transformation technology without precedent, where it takes the attack gains into account and uses the compromised states to design the corresponding controllers. In the backstepping design process, Nussbaum functions are presented to alleviate the influence of the unknown attack gains. Furthermore, we consider the actuator faults problem, which includes the loss of effectiveness and the bias fault. By skillfully designing the adaptive laws, the effect of actuator faults is completely eliminated. It is theoretically proved that the first proposed tracking control scheme can guarantee all signals in the closed-loop system are bounded and the output can track the desired reference signal. In addition, the second adaptive control scheme is also developed for the CPSs under the actuator faults and a more general assumption on the deception attacks is proposed simultaneously. Finally, the feasibility of the new proposed methods is verified by MATLAB simulation analysis.

Childhood maltreatment is an established risk factor for psychopathology. However, it remains unclear how childhood traumatic events relate to mental health problems and how the brain is involved. This study examined the serial mediation effect of brain morphological alterations and emotion-/reward-related functions on linking the relationship from maltreatment to depression. We recruited 156 healthy adolescents and young adults and an additional sample of 31 adolescents with major depressive disorder for assessment of childhood maltreatment, depressive symptoms, cognitive reappraisal and anticipatory/consummatory pleasure. Structural MRI data were acquired to identify maltreatment-related cortical and subcortical morphological differences. The mediation models suggested that emotional maltreatment of abuse and neglect, was respectively associated with increased gray matter volume in the ventral striatum and greater thickness in the middle cingulate cortex. These structural alterations were further related to reduced anticipatory pleasure and disrupted cognitive reappraisal, which contributed to more severe depressive symptoms among healthy individuals. The above mediating effects were not replicated in our clinical group partly due to the small sample size. Preventative interventions can target emotional and reward systems to foster resilience and reduce the likelihood of future psychiatric disorders among individuals with a history of maltreatment.

Background: Concerns have been raised regarding the impact of preoperative intravenous dexamethasone on postoperative glycemic control in diabetic patients undergoing total joint arthroplasty (TJA). This study aimed to determine relationships between preoperative different dexamethasone regimens and postoperative fasting blood glucose (FBG), as well as to identify risk factors for postoperative FBG ≥ 200 mg/dl in diabetic patients undergoing TJA., Methods: This retrospective study included 1216 diabetic patients undergoing TJA and categorized into group A (dexamethasone = 0 mg), group B (dexamethasone = 5 mg), and group C (dexamethasone = 10 mg). All dexamethasone was administered before skin incision. FBG levels were monitored until postoperative day (POD) 3. Analyses were conducted for periprosthetic joint infection (PJI) and wound complications during 90 days postoperatively. And the risk factors for postoperative FBG ≥ 200 mg/dl were identified., Results: Preoperative dexamethasone administration resulted in a transiently higher FBG on POD 0 and POD 1 (all P < 0.001). However, no differences were observed on POD 2 (P = 0.583) and POD 3 (P = 0.131) among three groups. While preoperative dexamethasone led to an increase in postoperative mean FBG and postoperative maximum FBG (all P < 0.001), no differences were found in wound complications (P = 0.548) and PJI (P = 1.000). Increased HbA1c and preoperative high FBG, but not preoperative dexamethasone, were identified as risk factors for postoperative FBG ≥ 200 mg/dl. Preoperative HbA1c level of ≥ 7.15% was associated with an elevated risk of postoperative FBG ≥ 200 mg/dl., Conclusions: Although preoperative intravenous administration of 5 mg or 10 mg dexamethasone in diabetic patients showed transient effects on postoperative FBG after TJA, no differences were found in the rates of PJI and wound complications during 90 days postoperatively. Notably, patients with a preoperative HbA1c level of ≥ 7.15% and elevated preoperative FBG may encountered postoperative FBG ≥ 200 mg/dl., (© 2023. The Author(s).)

Four new monoterpene indole alkaloids (1-4) together with twelve known alkaloids (5-16) were isolated from the roots of Alstonia rupestris. Compound 1 was the first example of C 2 -symmetric heteroyohimbine-type indole alkaloid homodimer obtained from natural plant resource. Their structures were elucidated on the basis of spectroscopic data. The absolute configuration of 1 was determined by comparison of its calculated and experimental electronic circular dichroism (ECD) spectra. All compounds were evaluated for their anti-inflammatory activities by measuring their NO inhibitory effects in LPS-stimulated RAW 264.7 cells. Compound 2 showed strong NO inhibition with IC 50 value of 4.2 ± 1.3 μM. Moreover, compound 2 could decrease the expressions of cyclooxygenase-2 (COX-2) and transforming growth factor beta-1 (TGF-β1)., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To analyze the influential factors of erectile dysfunction (ED) in patients with localized prostate cancer (LPC) after radical surgery., Methods: The clinical data of 150 male patients diagnosed with LPC and normal erectile function (EF) before surgery admitted to the Department of Urology of the Eastern Theatre General Hospital from January 2021 to January 2023 were retrospectively analyzed. The EF status of the patients 6 months after surgery was assessed using the International Erectile Function Index -5(IIEF-5). Age, Gleason score, PSA level, TNM stage, preoperative International prostatic symptom score (IPSS), preoperative prostate volume, smoking index, alcohol consumption index, educational level, comorbidities, operation mode, and psychosexual state were used as influencing factors to analyze their effects on postoperative ED., Results: Of the 150 patients, 88 had ED and 62 had normal EF. Univariate analysis showed that age, preoperative IPSS, preoperative prostate volume, comorbidities and sexual and psychological status were significantly correlated with postoperative ED. Further multivariate logistic regression analysis showed that age, preoperative prostate volume, comorbidities and sexual and psychological status were independent factors influencing the occurrence of ED after RP in LPC patients., Conclusion: The recovery of sexual function of patients with localized prostate cancer after radical surgery is generally poor, and the incidence of ED is high. Its independent influencing factors include age, preoperative prostate volume, comorbidities and sexual psychological state, etc. Correct intervention of different influencing factors is required in clinical work. In order to provide a better diagnosis and treatment scheme for LPC patients undergoing radical treatment, reduce the incidence of postoperative ED and improve the quality of life of patients after surgery.

Decalcified bone matrix (DBM) is a widely used alternative material for bone transplantation. In the DBM production process, an effective particle size and the highest utilization rate of raw materials can be achieved only through multiple high-speed circulating comminution. The rat posterolateral lumbar fusion model (PLF) is the most mature small animal model for the initial evaluation of the efficacy of graft materials for bone regeneration and spinal fusion. To evaluate the differences in the in vivo osteogenic effects of DBM pulverization through 1, 5, 9, and 14 high-speed cycles, sixty athymic rats were divided into six groups: single cycling crushing (CC1), 5 cycles of crushing (CC5), 9 cycles of crushing (CC9), 13 cycles of crushing (CC13), autogenous bone graft (ABG) and negative control (NC). Posterolateral lumbar fusion was performed. Six weeks after surgery, the bilateral lumbar fusion of athymic rats was evaluated through manual palpation, X-ray, micro-CT and histological sections. Rank data were tested by the rank-sum test, and nonparametric data were tested by the Kruskal‒Wallis H test. The manual palpation and X-ray results showed that the fusion rate did not significantly differ between the CC1, CC5, CC9, CC13 and ABG groups. However, cavities appeared in CC9 and CC13 on the micro-CT image. The bone mass (BV/TV) of CC1, CC5, CC9 and CC13 was better than that of the ABG group, while almost no osteogenesis was observed in the NC group. Histologically, there was no obvious difference between the four groups except that the CC9 group and CC13 group had more fibrous tissues in the new bone. In conclusion, DMB with different cycling crushing times has no obvious difference in fusion rate of PLF, but it is slightly better than the ABG group., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

As a major neuron type in the brain, the excitatory neuron (EN) regulates the lifespan in C. elegans. How the EN acquires senescence, however, is unknown. Here, we show that growth differentiation factor 11 (GDF11) is predominantly expressed in the EN in the adult mouse, marmoset and human brain. In mice, selective knock-out of GDF11 in the post-mitotic EN shapes the brain ageing-related transcriptional profile, induces EN senescence and hyperexcitability, prunes their dendrites, impedes their synaptic input, impairs object recognition memory and shortens the lifespan, establishing a functional link between GDF11, brain ageing and cognition. In vitro GDF11 deletion causes cellular senescence in Neuro-2a cells. Mechanistically, GDF11 deletion induces neuronal senescence via Smad2-induced transcription of the pro-senescence factor p21. This work indicates that endogenous GDF11 acts as a brake on EN senescence and brain ageing., (© 2023. The Author(s).)

Objective: To explore the risk factors of rebleeding in patients with obscure gastrointestinal bleeding (OGIB) after capsule endoscopy (CE), and construct a model to predict rebleeding. Methods: The data of patients with OGIB who underwent CE in Zhongda Hospital Affiliated to Southeast University from July 2018 to September 2021 were retrospectively analyzed. Follow-up data were obtained via electronic medical records or telephone interviews. Univariate and multivariate Cox regression models were performed to figure out the risk factors of rebleeding in OGIB patients. Then the optimal prediction model was determined and presented as a nomogram. The model was evaluated by C statistic, calibration curve and decision curve analysis. Results: One hundred and thirty patients with OGIB were included, including 64 females and 66 males, aged (55.8±17.2) years (18-87 years), and 39 (30.0%) cases developed rebleeding during follow-up. Univariate and multivariate Cox regression model analysis showed the duration of more than 2 weeks OGIB ( HR= 3.70, 95% CI : 1.85-7.42, P <0.001), a history of previous gastrointestinal bleeding ( HR= 5.25, 95% CI : 2.00-13.81, P <0.001), positive CE findings ( HR= 3.72, 95% CI : 1.66-8.33, P =0.001), and the lowest hemoglobin level before CE<80 g/L ( HR= 2.00, 95% CI : 1.02-3.84, P =0.044) were risk factors for rebleeding, while specific treatment ( HR= 0.25, 95% CI : 0.11-0.54, P <0.001) was a protective factor. The corresponding scores of the above five predictive factors were: OGIB duration>2 weeks: 79 points; Previous history of gastrointestinal bleeding: 100 points; The result of CE was positive: 79 points; Specific treatment:-85 points; Minimum hemoglobin before CE<80 g/L: 41 points. The prediction model constructed from the above five variables had good discriminative capability (concordance index=0.798, 95% CI : 0.732-0.865). The calibration curves showed high consistency between nomogram-predicted probabilities and actual observations. The decision curves showed that when the threshold probability was above 0.04, the use of the nomogram to predict rebleeding provided a greater net benefit than the assumption of "all patients rebleeding or no patients rebleeding". Conclusion: The prediction model established in this study has a good ability to predic rebleeding in patients with OGIB after CE examination.

Two new monoterpene indole alkaloids, Eleganine A ( 1 ) and Eleganine B ( 2 ), along with 11 known compounds (3-13) were isolated from the stems and leaves of Gelsemium elegans . Compound 1 is a gelsenicine-related monoterpenoid indole alkaloid possessing an iridoid unit. Their structures and absolute configurations of 1 - 2 were established by UV, IR, HR-ESI-MS, NMR spectroscopy, and electronic circular dichroism data analyses. All isolated compounds were evaluated for their anti-inflammatory and inhibiting glucose-induced mesanginal cell proliferation activities. None of them showed activity with IC 50 far beyond 50  μ M.

Gastric cancer (GC) is characterized by its vigorous chemoresistance to current therapies, which is attributed to the highly heterogeneous and immature phenotype of cancer stem cells (CSCs) during tumor initiation and progression. The secretory WNT2 ligand regulates multiple cancer pathways and has been demonstrated to be a potential therapeutic target for gastrointestinal tumors; however, its role involved in gastric CSCs (GCSCs) remains unclear. Here, we found that overexpression of WNT2 enhanced stemness properties to promote chemoresistance and tumorigenicity in GCSCs. Mechanistically, WNT2 was positively regulated by its transcription factor SOX4, and in turn, SOX4 was upregulated by the canonical WNT2/FZD8/β-catenin signaling pathway to form an auto-regulatory positive feedback loop, resulting in the maintenance of GCSCs self-renewal and tumorigenicity. Furthermore, simultaneous overexpression of both WNT2 and SOX4 was correlated with poor survival and reduced responsiveness to chemotherapy in clinical GC specimens. Blocking WNT2 using a specific monoclonal antibody significantly disrupted the WNT2-SOX4 positive feedback loop in GCSCs and enhanced the chemotherapeutic efficacy when synergized with the chemo-drugs 5-fluorouracil and oxaliplatin in a GCSC-derived mouse xenograft model. Overall, this study identified a novel WNT2-SOX4 positive feedback loop as a mechanism for GCSCs-induced chemo-drugs resistance and suggested that the WNT2-SOX4 axis may be a potential therapeutic target for gastric cancer treatment., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Lung cancer is a malignant tumor associated with high morbidity and mortality. Yiqi Yangjing recipe (YYR) is a formula of traditional Chinese medicine (TCM) that is commonly used for the treatment of lung cancer with good clinical efficacy. The specific anti-cancer mechanism of YYR is still unknown. We need to embark on a more in-depth pharmacological study of YYR to determine the complex compound ingredients, which could be promoted in clinical practice to achieve efficacy in prolonging recurrent metastasis of lung cancer., Methods: The cytotoxic effects of YYR on A549 cells were evaluated by Cell Counting Kit-8 (CCK-8) assay. The PFKFB3 -under-expressed and overexpressed A549 cell lines were constructed via PFK15 treatment and transfection, respectively. The effects of YYR on PFKFB3 messenger RNA (mRNA) and protein expression were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. The pro-apoptotic and anti-glycolytic abilities of YYR were measured using flow cytometry assay and hippocampal XF96 extracellular flux analyzer. An in vivo tumorigenicity assay was performed on nude mice to confirm the anti-cancer effects of YYR., Results: YYR has a noticeable cytotoxic activity on A549 cells, with the treatment with both YYR and PFK15 significantly inducing apoptosis. YYR and PFK15 treatment reduced the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) in A549 cells. Similar to PFK15, YYR can down-regulate PFKFB3 expression, and PFKFB3 overexpression suppressed the apoptosis, which was reversed by YYR. Animal experiments confirmed that YYR was able to inhibit tumor growth, induce tumor cell apoptosis, and down-regulate PFKFB3 in tumor tissues., Conclusions: This study demonstrated that YYR promoted lung cancer cell apoptosis and inhibited energy metabolism by targeting PFKFB3 . Furthermore, we believe that YYR may be a suitable supplement or alternative drug for lung cancer treatment., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-490/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Necrotizing enterocolitis (NEC) is a life-threatening, inflammatory disease affecting premature infants with intestinal necrosis, but the mechanism remains unclear. Neonatal macrophages are thought to play an important role in the pathogenesis of NEC through the production of proinflammatory cytokines. Restriction of cytokine expression in macrophages of NEC tissues may be beneficial. In adult macrophages, interfering with Rac1 has been shown to influence the expression of cytokines. Here, we investigated whether interfering with Rac1 in neonatal macrophages affects their inflammatory responses. First, we found that Rac1-activation was upregulated in the macrophages of rats with NEC model induction compared to controls. The M1 macrophages derived from human neonatal monocytes showed greater Rac1-activation than the M2 macrophages derived from the same monocytes. Inhibition of Rac1-activation by NSC23766 potently reduced the production of proinflammatory cytokines in these M1 macrophages. While neonatal monocytes differentiated into M1 macrophages in vitro, NSC23766 significantly altered cell function during the first six days of incubation with GM-CSF rather than during the subsequent stimulation phase. However, the same effect of NSC23766 was not observed in adult macrophages. Using mass spectrometry, Y-box binding protein 1 (YB1) was identified as being downregulated upon inhibition of Rac1-activation in the neonatal macrophages. Moreover, we found that inhibition of Rac1-activation shortens the poly A tail of PABPC1 mRNA, thereby reducing the translation of PABPC1 mRNA. Consequently, the downregulation of PABPC1 resulted in a reduced translation of YB1 mRNA. Furthermore, we found that TLR4 expression was downregulated in neonatal macrophages, while YB1 expression was reduced. Adding resatorvid (TLR4 signaling inhibitor) to the macrophages treated with NSC23766 did not further reduce the cytokine expression. These findings reveal a novel Rac1-mediated pathway to inhibit cytokine expression in neonatal M1 macrophages and suggest potential targets for the prevention or treatment of NEC., (© 2023. The Author(s).)

Objective: To observe the effects of electroacupuncture （EA） on hormone secretion function of ovarian granulosa cells and theca cells, as well as the expression changes of kisspeptin and kiss1r in rats with polycystic ovarian syndrome （PCOS）, so as to explore the mechanism of EA for relieving ovarian dysfunction in PCOS rats., Methods: Forty-eight SD female rats were randomly divided into control group, model group, EA group and flutamide group, with 12 rats in each group. PCOS rat model was replicated with the gavage of letrozole （0.1 mg/mL, 10 mL•kg -1 •d -1 ）. In the EA group, EA （2 Hz, 2 mA） was used to stimulate "Guanyuan" （CV4） for 20 min each time. In the flutamide group, flutamide solution （50 mg•kg -1 •d -1 ） was administrated by gavage. The treatments were given once daily for 14 days in each group. After the modeling and treatment, the body and ovarian weights of the rats were measured, and the ovarian index was calculated. Using HE staining, the morphological changes of ovary were observed. ELISA was adopted to detect the contents of testosterone （T）, luteinizing hormone （LH） and estradiol （E 2 ） in serum, the contents of E 2 and T in the culture medium of ovarian granulosa cells and theca cells, as well as the content of kisspeptin in the ovarian tissue. The positive expression of kisspeptin in ovary was observed by immunohistochemical method, and the protein expression of its receptor kiss1r was detected by Western blot., Results: Compared with the control group, the body and ovarian weights, ovarian index, the contents of T and LH in serum and that of T in the culture medium of theca cells, as well as the content and positive expression of kisspeptin in ovary were all increased （ P <0.01, P <0.05）； and the content of E 2 in the culture medium of granulosa cells was decreased （ P <0.01） in the model group. When compared with the model group, in the EA and flutamide groups, the body and ovarian weights, ovarian index, the contents of T and LH in serum and that of T in the culture medium of theca cells, as well as the content and expression of kisspeptin in ovary were all decreased （ P <0.01, P <0.05）； and the content of E 2 in the culture medium of granulosa cells was increased （ P <0.05, P <0.01）., Conclusion: EA regulates the serum sex hormone levels, the secretion function of the ovarian granulosa cells and theca cells, and the ovarian kisspeptin/kiss1r protein expression in PCOS rats, showing the similar effect as receptor blockade intervention. It is suggested that the improvement of EA in ovarian dysfunction of PCOS rats may be related to the kisspeptin/kiss1r system.

To evaluate the safety and efficacy of esophageal stent-in-stent (SIS) in patients with refractory esophageal self-expandable metal stents (SEMS). Case series study. Retrospective analysis was made on the patients with refractory esophageal SEMS treated with SIS technology in Zhongda Hospital Affiliated to Southeast University from June 2015 to June 2021. The success rate of stent removal and the incidence of adverse events were analyzed. A total of 12 patients were included, including 7 males and 5 females, aged 50-73 (62.7±8.5) years. The clinical success rate of the internal stents was 12/12, with the median retention time of [ M ( Q 1 , Q 3 ), 64.5 (52.0, 90.8)] days. The postoperative displacement rate and severe stenosis incidence were 1/12 and 3/12, respectively. The esophageal stents were successfully removed in one endoscopic session in all patients. A small amount of mucous membrane extravasation occurred in all patients after SIS, and no patients died after 90 days of follow-up.

Objective: To compare the diagnostic efficacy of AI-guided mpMRI-TRUS fusion assisted transperineal systematic biopsy, targeted biopsy and combined biopsy in the diagnosis of PCa, and to evaluate the clinical application value of combined biopsy., Methods: From April 2022, the general personal information and clinical data of patients with suspicious prostate lesions (PI-RADS≥3) detected by 3.0T mpMRI were collected, then underwent AI-guided mpMRI-TRUS fusion-assisted transperineal prostate biopsy. The data included age, PSA level, PV, PSAD, PI-RADS score, Gleason score of biopsy tissue, etc. The mpMRI image data were imported into the real-time fusion imaging system before biopsy. After image fusion, the suspected PCa lesion was taken as the target, 2 to 3 cores of targeted biopsy were first performed, then 12 cores of systematic biopsy were continued. The results of targeted biopsy + systematic biopsy were defined as the results of combined biopsy. The detection rate of PCa, CsPCa and pathological Gleason score were compared among different biopsy methods, and the diagnostic efficacy in different PI-RADS score groups was further evaluated., Results: A total of 118 PCa cases were detected in 220 patients enrolled in this study. The PCa detection rates of systematic biopsy and targeted biopsy were 40.45% and 43.64%, the result reveals no statistical significance (P=0.562). The PCa detection rate of combined biopsy was 53.64%, higher than single biopsy method and the differences were statistically significant (P<0.05). The detection rates of CsPCa in systematic biopsy and targeted biopsy were 28.18% and 37.27% which reveals significant statistical difference (P=0.042). The CsPCa detection rate of combined biopsy was 41.82%, higher than single biopsy method, the difference was statistically significant compared with systematic biopsy (P=0.003), but was not compared with targeted biopsy (P=0.330). In PI-RADS score 3 group, the PCa detection rate of systematic biopsy and targeted biopsy was 39.29% and 21.43%, which reveals no statistical significance (P=0.146). The PCa detection rate of combined biopsy was 50%, higher than single biopsy method, the difference was statistically significant compared with targeted biopsy (P=0.026), but was not compared with systematic biopsy (P=0.420). In PI-RADS 4 ~5 group, the PCa detection rate of systematic biopsy and targeted biopsy was 40.10%, and 46.88% which reveals no statistical significance (P=0.181). The PCa detection rate of combined biopsy was 54.17%, higher than single biopsy method, the difference was statistically significant compared with systematic biopsy (P=0.006), but was not compared with targeted biopsy (P=0.153). Among PCa patients detected by both systematic and targeted biopsy, 39 had concordant pathologic Gleason scores, 13 had escalating pathologic Gleason scores for systematic biopsy, and 18 had escalating pathologic Gleason scores for targeted biopsy., Conclusion: Compared with systematic biopsy, AI-guided mpMRI-TRUS image fusion assisted transperineal targeted prostate biopsy has a higher detection rate of CsPCa and is probably closer to the true pathological Gleason score. Compared with single biopsy, combined biopsy has higher diagnostic efficiency for PCa, which can be used as one of the options of prostate biopsy in clinical practice.

Sophorolipids are secondary metabolites produced during fermentation by nonpathogenic yeasts. These molecules are amphiphilic and consist of a hydrophilic sophora sugar moiety and a hydrophobic hydroxylated fatty acid. Based on their degree of esterification, sophorolipids can be divided into the acid and lactone types. Sophorolipids are highly promising biosurfactants with good antibacterial, antiviral, and other biological activities. Moreover, they are characterized by mildness, low toxicity, and environmental friendliness. However, their composition is quite complex, and effective methods for their quality evaluation are lacking. Since sophorolipids do not absorb ultraviolet (UV) light, common UV detectors are unsuitable for fingerprint establishment. In this study, we first selected a charged aerosol detector (CAD) to establish the ultra-high performance liquid chromatography (UHPLC) fingerprint of sophorolipids. The detector had high sensitivity, good reproducibility, and excellent suitability for the detection of substances with no or weak ultraviolet absorption. We then evaluated the similarities between 17 batches of sophorolipid samples. The samples were extracted by ultrasound for 10 min in 80% ethanol aqueous solution at a liquid-solid ratio of 10∶1 (mL/g) and then separated on a Thermo Fisher Scientific Hypersil Gold chromatographic column (150 mm×2.1 mm, 1.9 μm). Separation was performed using acetonitrile-0.01% (v/v) formic acid aqueous solution as the mobile phase via gradient elution. The flow rate was 0.2 mL/min, and the column temperature was 40 ℃. The CAD was used under the following conditions: power function of 1.0, data rate of 5 Hz, filter constant of 3.6, and evaporation temperature of 45 ℃. The chromatograms and retention times of the sophorolipids were compared, and 16 common peaks with strong responses, good resolutions, and stable retention times were selected as characteristic peaks. Oleic acid was chosen as the reference peak because it achieved good separation and a strong chromatographic response in all batches of samples. UHPLC-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was used to identify chromatographic peaks in the sophorolipid fingerprints. The results were combined with the retention time rule of the sophorolipids, leading to their identification based on matching with the results of the primary database, the precise relative molecular mass and fragmentation rule of secondary fragments, a self-built database, and the PubChem database. Sixteen compounds were identified, including eight acid sophorolipids, six lactone sophorolipids, and two aliphatic acids. The results of precision, repeatability, and 24 h stability tests indicated that the relative standard deviations (RSDs) of the retention times and peak areas of the 15 characteristic peaks relative to the control peak (oleic acid) were less than 3.0% ( n =6). Seventeen batches of sophorolipid samples were analyzed, and the similarity values of all fingerprints were found to be 0.965 or higher. Little differences in chemical composition were observed among the different batches of sophorolipid samples, and the quality of the sophorolipids was relatively consistent. The fingerprint established in this study is stable and reliable; it can be used for the quality evaluation of sophorolipids and lays a solid foundation for future research on production technology and the development and utilization of sophorolipids. The successful application of a universal CAD to the fingerprint establishment of sophorolipids also provides a reliable solution for the fingerprint establishment of substances with no or weak ultraviolet absorption.

In recent years, the contamination of antibiotics and their resistance genes (ARGs) has attracted the extensive attention of researchers at home and abroad. Soil is an important sink for the migration and transformation of antibiotics and ARGs, which pose a threat to soil organisms and human health. According to the relevant investigations in the past 15 years, the soil has been polluted by antibiotics to varying degrees in China. Bioremediation is a green and environment-friendly remediation technology, which has great potential in the remediation of antibiotic-contaminated soil. This review summarized the spatial and temporal characteristics of antibiotic pollution of soils in China in the past 15 years and the application of plants, animals, and microorganisms in the remediation of antibiotic-contaminated soil. In particular, the recent research advances of microbial electrochemical systems in removing antibiotics and ARGs in soil were reviewed, and the unaddressed issues of relevant research and the direction of future development were proposed, in order to provide a scientific basis for soil pollution remediation.

The cuticle of plants, a hydrophobic membrane that covers their aerial organs, is crucial to their ability to withstand biotic and abiotic stressors. Fruit is the reproductive organ of plants, and an important dietary source that can offer a variety of nutrients for the human body, and fruit cuticle performs a crucial protective role in fruit development and postharvest quality. This review discusses the universality and diversity of the fruit cuticle composition, and systematically summarizes the metabolic process of fruit cuticle, including the biosynthesis, transport and regulatory factors (including transcription factors, phytohormones and environmental elements) of fruit cuticle. Additionally, we emphasize the postharvest functions and postharvest regulatory technologies of fruit cuticle, and propose future research directions for fruit cuticle., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Continuous renal replacement therapy (CRRT) is widely used for treating critically-ill patients in the emergency department in China. Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation during CRRT. Regional citrate anticoagulation (RCA) has been shown to potentially be safer and more effective and is now recommended as the preferred anticoagulant method for CRRT. However, there is still a lack of unified standards for RCA management in the world, and there are many problems in using this method in clinical practice. The Emergency Medical Doctor Branch of the Chinese Medical Doctor Association (CMDA) organized a panel of domestic emergency medicine experts and international experts of CRRT to discuss RCA-related issues, including the advantages and disadvantages of RCA in CRRT anticoagulation, the principle of RCA, parameter settings for RCA, monitoring of RCA (mainly metabolic acid-base disorders), and special issues during RCA. Based on the latest available research evidence as well as the paneled experts' clinical experience, considering the generalizability, suitability, and potential resource utilization, while also balancing clinical advantages and disadvantages, a total of 16 guideline recommendations were formed from the experts' consensus., (© 2023. The Author(s).)

Objective: To evaluate the consistency of the Gleason scores of PCa patients based on preoperative biopsy with those from postoperative pathology, identify the possible factors influencing results of scoring, and construct a risk scoring model., Methods: We collected the demographic and clinical data on the patients with PCa confirmed by preoperative prostate biopsy or postoperative pathology and treated by radical prostatectomy within 6 months after diagnosis. Using paired sample t-test, we identified the difference between the Gleason scores based on preoperative biopsy and those from postoperative pathology, analyzed the demographic and clinical data on the patients for relevant factors affecting the consistency of the Gleason scores, and calculated and visualized the relative risk values of the factors through Poisson regression. From the continuous variables with statistical significance, we screened independent risk factors for the difference in the Gleason scores by Lasso regression analysis, established a risk scoring model, generated risk coefficients, and evaluated the predictive ability of the model using the ROC curve. Based on the results of imaging examination with statistically significant differences, we constructed a column chart by logistic regression and evaluated the predictive validity of the chart using calibration curves, decision curves and ROC curves., Results: The results of paired sample t-test for 210 PCa patients showed statistically significant differences between the Gleason scores from preoperative biopsy and those from postoperative pathology (P < 0.001). There were significant differences in the body weight, BMI and PSA level as well as in all other factors but prostate calcification between the patients with consistent and those with inconsistent Gleason scores (all P < 0.05). An 8-factor prediction model was successfully constructed, which could predict the consistency of Gleason scores, with a better predicting performance than the single indicator within the model. The nomogram exhibited a C-index value of 0.85, with the calibration curve similar to the standard one, the threshold of the decision curve 0.10－0.92, and the area under the ROC curve higher than other predictive indicators., Conclusion: Based on the demographic and clinical data on PCa patients, a risk prediction model and a column chart were successfully constructed, which could effectively predict the difference between the Gleason scores from preoperative prostate biopsy and those from postoperative pathology.

Prostate cancer（PCa）is the most common malignant tumor in male genitourinary system. In China, the incidence of PCa is increasing significantly, which seriously endangers the physical and mental health of Chinese men. Programmed cell death（PCD）is a kind of active and orderly cell death mode, which exists widely in the process of life activities. With the deepening understanding of PCD, more and more studies have found that different types of PCD are closely related to PCa.This article mainly reviews therole of programmed cell death in the diagnosis and treatment of prostate cancer.

Since primary retroperitoneal liposarcoma (PRPLS) is rare in the clinic, related clinical studies are lacking. The present study was designed to investigate the predictive factors of short-term (≤1 year) recurrence (STR) and construct a novel nomogram of local recurrence-free survival (LRFS) for surgically resected PRPLS. A total of 128 PRPLS cases who underwent radical surgery were retrospectively analyzed. Based on the interval from the operation to tumor recurrence, the predictors of STR were screened using univariate and multivariate logistic regression analyses. Cox proportional hazard regression models were applied to identify the predictors of LRFS. Furthermore, the independent predictors acquired from multivariate analyses were used to construct a nomogram. Multivariate logistic regression analysis revealed that age ≥55 years [odds ratio (OR)=5.607, P=0.010], operative time ≥260 min (OR=9.716, P=0.005) and tumor necrosis (OR=3.781, P=0.037) were independent risk factors of STR for PRPLS. In the Cox regression analysis, clinical symptoms [hazard ratio (HR)=1.746, P=0.017], resection method (OR=0.370, P=0.021) and de-differentiated histological subtype (HR=1.975, P=0.048) were identified as independent predictors of LRFS. Subsequently, the independent predictors acquired from multivariate analyses were used to construct a nomogram for LRFS. Age, operative time, tumor necrosis, clinical symptoms, resection method and histological subtype were related to recurrence for surgically resected PRPLS and a novel nomogram was constructed based on the above predictors., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Yu et al.)

Objective: To evaluate the pathological characteristics of endoscopic submucosal dissection (ESD) specimens for early gastric cancer and precancerous lesions, accumulating experience for clinical management and pathological analysis., Methods: A total of 411 cases of early gastric cancer or precancerous lesions underwent ESD. According to the Japanese guidelines for ESD treatment of early gastric cancer and classification of gastric carcinoma, the clinicopathological data, pathologic evaluation, concordance rate of pathological diagnosis between preoperative endoscopic forceps biopsies and their ESD specimens (in 400 cases), as well as the risk factors of non-curative resection of early gastric cancer, were analyzed retrospectively., Results: 23.4% (96/411) of the 411 cases were adenoma/low-grade dysplasia and 76.6% (315/411) were early gastric cancer. The latter included 28.0% (115/411) non-invasive carcinoma/high-grade dysplasia and 48.7% (200/411) invasive carcinoma. The concordance rate of pathological diagnosis between endoscopic forceps biopsies and ESD specimens was 66.0% (264/400), correlating with pathological diagnosis and lesion location ( P < 0.01). The rate of upgraded diagnosis and downgraded diagnosis after ESD was 29.8% (119/400) and 4.2% (17/400), respectively. Among the 315 cases of early gastric cancer, there were 277 cases (87.9%) of differentiated type and 38 cases (12.1%) of undifferentiated type. In the study, 262 cases (83.2%) met with absolute indication, while 53 cases (16.8%) met relative indication. En bloc and curative resection rates were 98.1% and 82.9%, respectively. Risk factors for non-curative resection included a long diameter >20 mm ( OR =3.631, 95% CI : 1.170-11.270, P =0.026), tumor infiltration into submucosa ( OR =69.761, 95% CI : 21.033-231.376, P < 0.001)and undifferentiated tumor histology ( OR =16.950, 95% CI : 4.585-62.664, P < 0.001)., Conclusion: Several subjective and objective factors, such as the limitations of biopsy samples, the characteristics and distribution of the lesions, different pathological understanding, and the endoscopic sampling and observation, can lead to the differences between the preoperative and postoperative pathological diagnosis of ESD. In particular, the pathological upgrade of postoperative diagnosis was more significant and should receive more attention by endoscopists and pathologists. The curative resection rate of early gastric cancer in ESD was high. Non-curative resection was related to the long diameter, the depth of tumor invasion and histological classification. ESD can also be performed in undifferentiated early gastric cancer if meeting the indication criteria. The comprehensive and standardized pathological analysis of ESD specimens is clinically important to evaluate the curative effect of ESD operation and patient outcomes.

We propose a scheme for the creation of stable optical Ferris wheel (OFW) solitons in a nonlocal Rydberg electromagnetically induced transparency (EIT) medium. Depending on a careful optimization of both the atomic density and the one-photon detuning, we obtain an appropriate nonlocal potential provided by the strong interatomic interaction in Rydberg states that can perfectly compensate for the diffraction of the probe OFW field. Numerical results show that the fidelity remains larger than 0.96, while the propagation distance has exceeded 160 diffraction lengths. Higher-order OFW solitons with arbitrary winding numbers are also discussed. Our study provides a straightforward route to generate spatial optical solitons in the nonlocal response region of cold Rydberg gases.

All-solid-state lithium-sulfur batteries (ASSLSBs) have high reversible characteristics owing to the high redox potential, high theoretical capacity, high electronic conductivity, and low Li + diffusion energy barrier in the cathode. Monte Carlo simulations with cluster expansion, based on the first-principles high-throughput calculations, predicted a phase structure change from Li 2 FeS 2 ( P 3̄ M 1) to FeS 2 ( PA 3̄) during the charging process. LiFeS 2 is the most stable phase structure. The structure of Li 2 FeS 2 after charging was FeS 2 ( P 3̄ M 1). By applying the first-principles calculations, we explored the electrochemical properties of Li 2 FeS 2 after charging. The redox reaction potential of Li 2 FeS 2 was 1.64 to 2.90 V, implying a high output voltage of ASSLSBs. Flatter voltage step plateaus are important for improving the electrochemical performance of the cathode. The charge voltage plateau was the highest from Li 0.25 FeS 2 to FeS 2 and followed from Li 0.375 FeS 2 to Li 0.25 FeS 2 . The electrical properties of Li x FeS 2 remained metallic during the Li 2 FeS 2 charging process. The intrinsic Li Frenkel defect of Li 2 FeS 2 was more conducive to Li + diffusion than that of the Li 2 S Schottky defect and had the largest Li + diffusion coefficient. The good electronic conductivity and Li + diffusion coefficient of the cathode implied a better charging/discharging rate performance of ASSLSBs. This work theoretically verified the FeS 2 structure after Li 2 FeS 2 charging and explored the electrochemical properties of Li 2 FeS 2 .

Objective: To verify the effect and safety of low-intensity extracorporeal shockwave therapy (Li-ESWT) in improving the symptoms of ED, and provide some reference for further related large-scale clinical trials., Methods: Twenty-six patients diagnosed with ED received Li-ESWT with an energy of 0.09 mJ/mm2 for 20 minutes once a week for 6 four-week courses. Before and at 3, 6, 9, and 12 months after treatment, we obtained the IIEF-5 and Erectile Hardness Scale (EHS) scores of the patients using questionnaires, recorded the incidence of treatment-related adverse reactions, compared the erectile function of the patients before and after treatment, and evaluated the effect and safety of Li-ESWT in improving ED-related symptoms., Results: Compared with the baseline, the IIEF-5 scores of the patients were significantly increased (P < 0.01) while the EHS scores slightly increased at 3 months after Li-ESWT treatment (P > 0.05), both IIEF-5 and EHS scores were dramatically increased at 6 months (P < 0.01), and both significantly higher than at 3 months. At 9 months, EHS scores remained remarkably higher than the baseline (P < 0.01) although IIEF-5 scores slightly lower than at 6 months. At 12 months, however, IIEF-5 scores decreased, though still significantly higher than the baseline (P < 0.01), and EHS scores became lower than at 6 and 9 months (P < 0.05) but still markedly higher than before treatment (P < 0.05). Adverse reactions observed during the intervention mainly included pruritus (4.35%), pain (2.90%), paresthesia (2.17%), and petechiae/ecchymosis (2.90%)., Conclusion: Li-ESWT can increase the IIEF-5 and EHS scores and improve the clinical symptoms of ED patients, with a low incidence of adverse reactions during the treatment.

In China, Hyphantria cunea (Drury) is an invasive phytophagous pest; it attacks nearly all species of defoliated trees. To develop integrated pest management programs (IPM) for H. cunea, we need to ensure the availability of insects by mass-rearing them on artificial diets under laboratory conditions. This study compared the growth characteristics, nutritional indices, growth indices, and digestive enzyme activity of insects reared on Pterocarya stenoptera C.DC (Fagales: Juglandaceae), the Chinese wingnut, and an artificial diet. We also investigated the correlation between diet components and growth indices using principal components analysis and Pearson correlation analysis. We found that mass-rearing of H. cunea on an artificial diet was feasible. It led to a shorter developmental period, with heavier larvae and pupae than natural diets. The principal components analysis indicated that the growth indices and α-Amylase were significantly positively associated with PC1, which explained 82.45% of the total data variability. Pearson correlation analysis showed a significant correlation between digestion, absorption parameters, and growth. Developing a mass-rearing program to produce H. cunea on an artificial diet will be valuable for improving IPM strategies. Understanding the mechanism of the responses of phytophagous insect populations to anthropogenic diet regulation can provide new ideas and methods for pest control., (© The Author(s) 2022. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)