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The commercialized genetically modified (GM) papaya cultivars have protected papaya from the devastating disease caused by papaya ringspot virus (PRSV). However, papaya leaf distortion mosaic virus (PLDMV), which causes similar infection symptoms but is serologically distinct from PRSV, was found as a competitive threat to the papaya industry. Our study surveyed the occurrence of PRSV and PLDMV as well as the transgenic markers of the 35S promoter from cauliflower mosaic virus (CaMV 35S) and the neomycin phosphotransferase II (NPT II) gene in feral papaya plants, which were found frequently growing outside of cultivated papaya fields on Hainan Island. In total, 123 feral papayas, comprising 62 (50.4%) GM plants and 61 (49.6%) non-GM ones, were sampled. Among them, 23 (18.7%) were positive for PRSV, 49 (39.8%) were positive for PLDMV, including 5 plants co-infected by PRSV and PLDMV, and 56 (45.5%) plants were free of either virus. In traditional papaya growing regions, we detected fewer PRSV-infected plants (2 in 33, 6%) than in other regions (21 in 90, 23%). But overall, whether transgenic or not made no significance in PRSV incidence ( P =0.230), with 9 PRSV-infected plants among 62 GM papayas and 14 among 61 non-GM papayas. Phylogenetic and genetic differentiation analysis showed a clear correlation between PRSV and PLDMV populations and their geographical origins. Negative selection was estimated for the selected gene regions of both viruses. Notably, PLDMV has deviated from neutral evolution and experienced population expansion, exhibiting increased genetic diversity and is becoming the predominant threat to papaya in Hainan.

A novel series of excited-state intramolecular proton transfer (ESIPT) emitters, namely, DPNA , DPNA-F , and DPNA- t Bu , endowed with dual intramolecular hydrogen bonds, were designed and synthesized. In the condensed phase, DPNAs exhibit unmatched absorption and emission spectral features, where the minor 0-0 absorption peak becomes a major one in the emission. Detailed spectroscopic and dynamic approaches conclude fast ground-state equilibrium among enol-enol (EE), enol-keto (EK), and keto-keto (KK) isomers. The equilibrium ratio can be fine-tuned by varying the substitutions in DPNA s. Independent of isomers and excitation wavelength, ultrafast ESIPT takes place for all DPNAs , giving solely KK tautomer emission maximized at >650 nm. The spectral temporal evolution of ESIPT was resolved by a state-of-the-art technique, namely, the transient grating photoluminescence (TGPL), where the rate of EK* → KK* is measured to be (157 fs) -1 for DPNA- t Bu , while a stepwise process is resolved for EE* → EK* → KK*, with a rate of EE* → EK* of (72 fs) -1 . For all DPNAs , the KK tautomer emission shows a narrowband emission with high photoluminescence quantum yields (PLQY, ∼62% for DPNA in toluene) in the red, offering advantages to fabricate deep-red organic light-emitting diodes (OLED). The resulting OLEDs give high external quantum efficiency with a spectral full width at half-maximum (FWHM) as narrow as ∼40 nm centered at 666-670 nm for DPNAs , fully satisfying the BT. 2020 standard. The unique ESIPT properties and highly intense tautomer emission with a small fwhm thus establish a benchmark for reaching red narrowband organic electroluminescence.

Purpose: Robot-assisted total hip arthroplasty (RA-THA) helps with precise orientation of the prosthesis, but some RA-THA procedures are aborted intraoperatively and are converted to manual total hip arthroplasty (THA). This study aimed to analyse why RA-THA is sometimes aborted intraoperatively and to make recommendations accordingly., Methods: A total of 429 consecutive Mako THA cases in our prospective database from August 2018 to June 2021 were included in our study. All robotic procedures aborted intraoperatively for any reason were recorded. The patients' demographics, diagnoses, and surgeons' information were included in the statistical analysis to pinpoint the risk factors for intraoperative robot to manual conversion., Results: Intraoperative RA-THA abortions occurred in 17 cases (3.96%) and the patients had to be converted to manual THA. The adverse events leading to intraoperative abortions included pelvic array loosening or malposition (5, 1.17%), inaccurate bone mapping or construction (6, 1.40%), inaccurate initial registration (4, 0.93%), and other reasons (2, 0.47%)., Conclusion: Robot-related adverse events could be found in all perioperative steps of RA-THA, and some of these events might result in intraoperative abortion. Complex hip disease was a statistically significant factor for an increased risk of intraoperative abortion of RA-THA. Standardized surgical procedures and preoperative assessments can be helpful in reducing the rate of RA-THA abortions., (© 2024. The Author(s) under exclusive licence to SICOT aisbl.)

Chronic myelogenous leukemia (CML) is a hematological malignancy originating from the pluripotent hematopoietic stem cells. Imatinib is the first generation of small molecule tyrosine kinase inhibitors (TKI) that revolutionized the treatment of CML. Flumatinib, as a novel oral TKI that independently developed in China, which can be used as a preferred treatment for CML. Basic researches suggested that the inhibitory effect of flumatinib on CML cell lines is stronger than imatinib. Flumatinib demonstrated that it has better efficacy than imatinib on CML in clinical trials and in real world studies. Flumatinib also showed a higher potency against CML with specific mutations, Ph(+) acute lymphoblastic leukemia and some solid tumors. The adverse events are manageable and tolerable.

Introduction: Observational research is important for understanding the real-world benefits of advancements in lung cancer care. Integrated health care systems, such as Kaiser Permanente Northern California, have extensive electronic health records suitable for such research, but the generalizability of their populations is often questioned., Methods: Leveraging data from the California Cancer Registry, the authors compared distributions of demographic and clinical characteristics, in addition to neighborhood and environmental conditions, between patients diagnosed with lung cancer from 2015 through 2019 at Kaiser Permanente Northern California, National Cancer Institute-designated cancer centers (NCICCs), and all other non-NCICC hospitals within the same catchment area., Results: Of 20,178 included patients, 30% were from Kaiser Permanente Northern California, 8% from NCICCs, and 62% from other non-NCICC hospitals. Compared to NCICC patients, Kaiser Permanente Northern California patients were more similar to other non-NCICC patients on most characteristics. Compared to other non-NCICC patients, Kaiser Permanente Northern California patients were slightly older, more likely to be female, and less likely to be Hispanic or Asian/Pacific Islander and to reside in lower socioeconomic status (SES) neighborhoods. In contrast, NCICC patients were younger, less likely to be female or from non-Asian/Pacific Islander minoritized racial groups, and more likely to present with early-stage disease and adenocarcinoma and to reside in neighborhoods with higher SES and lower air pollution than Kaiser Permanente Northern California or other non-NCICC patients., Discussion: Patients from Kaiser Permanente Northern California, compared to NCICCs, are more broadly representative of the underlying patient population with lung cancer., Conclusion: Research using electronic health record data from integrated health care systems can contribute generalizable real-world evidence to benchmark and improve lung cancer care.

Objective: Little research has investigated factors that determine whether people falter in the face of an obstacle or successfully follow through on an initial commitment to act. We integrated multiple theories (the Reasoned Action Approach [RAA], Prototype Willingness Model, and anticipated regret theory) to test which factors predict initial commitment to register as an organ donor and to discover whether different factors predict initial commitment vs. following through with registration., Methods: Participants from a nationally representative UK sample (N = 1,008) reported their beliefs about organ donation and indicated their decision to register. An obstacle that participants could not foresee was that they had to complete registration in a second survey 3 days after making their initial commitment., Results: Findings showed that 14.8% of participants followed through, 19.7% demonstrated initial commitment, and 65.5% declined to register. Linear discriminant function analysis derived two functions that distinguished these registration patterns. The first function discriminated participants who declined to register from the other groups. The declined group had lower scores on RAA variables compared to their counterparts. The second function distinguished participants who made an initial commitment to register from those who followed through. Follow-through was associated with less anticipated negative affect, more favorable descriptive norms, and stronger identification with organ donors., Conclusions: The present findings indicate that even modest friction leads to a large reduction in follow-through. Moreover, different factors influence initial commitment vs. following through. Whereas RAA variables predicted initial commitment, following through was a function of anticipated negative affect and social processes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yang, Sheeran. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: To demonstrate the effectiveness and feasibility of robotic portal resection (RPR) for mediastinal tumour using a prospectively collected database., Methods: Data from 73 consecutive patients with mediastinal tumours who underwent RPRs were prospectively collected from August 2018 to April 2023. All patients underwent chest and abdominal enhanced computed tomography (CT) and preoperative multidisciplinary team (MDT) discussion. The patients were stratified into two groups based on tumour size: Group A (tumour size < 4 cm) and Group B (tumour size ≥ 4 cm). General clinical characteristics, surgical procedures, and short outcomes were promptly recorded., Results: All of the cases were scheduled for RPRs. One patient (1/73, 1.4%) was switched to a small utility incision approach because of extensive pleural adhesion. Two patients (2.8%) converted to sternotomy, however, no perioperative deaths occurred. Most of the tumours were located in the anterior mediastinum (51/73, 69.9%). Thymoma (27/73, 37.0%) and thymic cyst (16/73, 21.9%) were the most common diagnoses. The median diameter of tumours was 3.2 cm (IQR, 2.4-4.5 cm). The median total operative time was 61.0 min (IQR, 50.0-90.0 min). The median intraoperative blood loss was 20 mL (IQR, 5.0-30.0 ml), and only one patient (1.4%) experienced an intraoperative complication. The median length of hospital stay was 3 days (IQR, 2-4 days). Compared with Group A, the median total operative time and console time of Group B were significantly longer (P = 0.006 and P = 0.003, respectively). The volume of drainage on the first postoperative day was greater in group B than in group A (P = 0.013)., Conclusion: RPR is a safe and effective technique for mediastinal tumour treatment, which can expand the application of minimally invasive surgery for the removal of complicated mediastinal tumours., (© 2024. The Author(s).)

In this study, we focused on grapevine-endophyte interactions and reprogrammed secondary metabolism in the host plant due to defense against the colonization of endophytes. Thus, the transcriptional responses of tissue cultured grapevine seedlings ( Vitis vinifera L. cv.: Cabernet Sauvignon) to two fungal endophytes Epicoccum layuense R2-21 (Epi R2-21) and Alternaria alternata XHYN2 (Alt XHYN2) at three different time points (6 h, 6 d, 15 d) were analyzed. As expected, a total of 5748 and 5817 differentially expressed genes (DEGs) were separately initiated in Epi R2-21 and Alt XHYN2 symbiotic tissue cultured seedlings compared to no endophyte treatment. The up-regulated DEGs at all time points in Epi R2-21- or Alt XHYN2-treated seedlings were mainly enriched in the flavonoid biosynthesis, phenylpropanoid biosynthesis, phenylalanine metabolism, stilbenoid, diarylheptanoid and gingerol biosynthesis, and circadian rhythm-plant pathways. In addition, the up-regulated DEGs at all sampling times in Alt XHYN2-treated tissue cultured seedlings were enriched in the plant-pathogen interaction pathway, but appeared in Epi R2-21 symbiotic seedlings only after 15 d of treatment. The down-regulated DEGs were not enriched in any KEGG pathways after 6 h inoculation for Epi R2-21 and Alt XHYN2 treatments, but were enriched mainly in photosynthesis-antenna proteins and plant hormone signal transduction pathways at other sampling times. At three different time points, a total of 51 DEGs (all up-regulated, 1.33-10.41-fold) were involved in secondary metabolism, and 22 DEGs (all up-regulated, 1.01-8.40-fold) were involved in defense responses in endophytic fungi symbiotic tissue cultured seedlings. The protein-protein interaction (PPI) network demonstrated that genes encoding CHS ( VIT&#95;10s0042g00920 , VIT&#95;14s0068g00920 , and VIT&#95;16s0100g00910 ) and the VIT&#95;11s0065g00350 gene encoding CYP73A mediated the defense responses, and might induce more defense-associated metabolites. These results illustrated the activation of stress-associated secondary metabolism in the host grapevine during the establishment of fungi-plant endophytism. This work provides avenues for reshaping the qualities and characteristics of wine grapes utilizing specific endophytes and better understanding plant-microbe interactions.

Regulation of gut microbiota and its impact on human health is the theme of intensive research. The incidence and prevalence of atrial fibrillation (AF) are continuously escalating as the global population ages and chronic disease survival rates increase; however, the mechanisms are not entirely clarified. It is gaining awareness that alterations in the assembly, structure, and dynamics of gut microbiota are intimately engaged in the AF progression. Owing to advancements in next-generation sequencing technologies and computational strategies, researchers can explore novel linkages with the genomes, transcriptomes, proteomes, and metabolomes through parallel meta-omics approaches, rendering a panoramic view of the culture-independent microbial investigation. In this review, we summarized the evidence for a bidirectional correlation between AF and the gut microbiome. Furthermore, we proposed the concept of "gut-immune-heart" axis and addressed the direct and indirect causal roots between the gut microbiome and AF. The intricate relationship was unveiled to generate innovative microbiota-based preventive and therapeutic interventions, which shed light on a definite direction for future experiments., (© 2023. The Author(s).)

Numerous agents such as near-infrared dyes that are characterized by specialized cancer imaging and cytotoxicity effects have key roles in cancer diagnosis and therapy via molecularly targeting special biological tissues, organelles and processes. In the present study, a novel fluorescent compound was demonstrated to inhibit cancer cell proliferation in a zebrafish model with slight in vivo toxicity. Further studies demonstrated selective staining of cancer cells and even putative cancer stem cells via accumulation of the dye in the mitochondria of cancer cells, compared with normal cells. Moreover, this compound was also used to image cancer cells in vivo using a zebrafish model. The compound displayed no apparent toxicity to the host animal. Overall, the data indicated that this compound was worthy of further evaluation due to its low toxicity and selective cancer cell imaging and killing effects. It could be a useful tool in cancer research., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Ren et al.)

Background: We aimed to investigate the impact of the number of harvested lymph nodes (LNs) on the overall survival (OS) and disease-free survival (DFS) of patients with clinical node-negative (cN0) non-small-cell lung cancer (NSCLC)., Patients and Methods: A total of 2247 patients with cN0 NSCLC between 2001 and 2014 were included. Scatter plots of hazard ratios from Cox proportional hazards models against the number of harvested LNs were created, and curves were fitted using a LOWESS smoother. Chow test was used to determine the cut-off points for the optimal number of harvested LNs. Long-term survival was compared between groups divided by the cut-off points., Results: The increasing numbers of harvested LNs and N2 level LNs were independent factors favoring OS and DFS. Seventeen LNs and 10 N2 level LNs were determined as the optimal cut-off points. The patients with ≥17 harvested LNs had a better OS (P = .001) and DFS (P = .002), while the patients with ≥10 harvested N2 level LNs also had a better OS (P < .001) and DFS (P = .001). The increasing numbers of harvested LNs and N2 level LNs were independent prognostic factors associated with prolonged OS and DFS only in patients with clinical T2 (cT2) NSCLC., Conclusions: The increasing numbers of harvested LNs and N2 level LNs were associated with better OS and DFS in cN0 NSCLC patients that were suitable for lobectomies. At least 17 LNs and 10 N2 level LNs were required to be harvested, especially in cT2 patients., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Although robotic segmentectomy has been applied for the treatment of small pulmonary lesions for many years, studies on the learning curve of robotic segmentectomy are quite limited. Thus, we aim to investigate the learning curve of robotic portal segmentectomy with 4 arms (RPS-4) using prospectively collected data in patients with small pulmonary lesions. One hundred consecutive patients with small pulmonary lesions who underwent RPS-4 between June 2018 and April 2021 were included in the study. Da Vinci Si/Xi systems were used to perform RPS-4. The mean operative time, console time, and docking time for the entire cohort were 119.2 ± 41.6, 85.0 ± 39.6, and 6.6 ± 2.8 min, respectively. The learning curve of RPS-4 can be divided into three different phases: 1-37 cases (learning phase), 38-78 cases (plateau phase), and > 78 cases (mastery phase). Moreover, 64 cases were required to ensure acceptable surgical outcomes. The total operative time (P < 0.001), console time (P < 0.001), blood loss (P < 0.001), and chest tube duration (P = 0.014) were reduced as experience increased. In conclusion, the learning curve of RPS-4 could be divided into three phases. 37 cases were required to pass the learning phase, and 78 cases were needed to truly master this technique., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Objectives: The interferon regulatory factor (IRF) family of proteins are involved in tumor progression. However, the role of IRF5 in tumorigenesis remains unknown. In this study we aimed to elucidate the functions of IRF5 in the progression of hepatocellular carcinoma (HCC)., Methods: IRF5 expression in HCC was analyzed through quantitative polymerase chain reaction (qPCR), western blot, and immunohistochemistry (IHC), etc. The Cell Counting Kit 8 (CCK8) assay, anchorage-independent assay, and EdU assay were used to evaluate the role of IRF5. The molecular mechanisms were studied by analyzing the metabolites with mass spectrum and immunoprecipitation., Results: IRF5 was upregulated in HCC. Interfering with IRF5 inhibited the proliferation and tumorigenic potential of HCC cells. When studying the molecular mechanism, IRF5 was found to upregulate the expression of lactate dehydrogenase A (LDHA) and promoted glycolysis. Additionally, tripartite motif containing 35 (TRIM35) interacted with IRF5, promoting its ubiquitination and degradation. In the clinically obtained HCC samples, TRIM35 was negatively correlated with the expression of IRF5., Conclusion: These findings reveal the oncogenic function of IRF5 in the progression of HCC by enhancing glycolysis, further supporting the potential of IRF5 as a viable target for HCC therapy., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Although learning health information is beneficial for physical well-being, many people opt to avoid learning this information due to its potentially threatening nature. Such avoidance can lead to delays in seeking treatment., Purpose: This study tested the effectiveness of a self-regulation technique, mental contrasting (MC), specifically MC of a negative future with a positive current reality, in reducing health information avoidance regarding skin cancer (melanoma). We hypothesized that participants who engaged in MC would be more likely to choose to learn about their melanoma risk than those who completed a control, reflection activity., Methods: We conducted a randomized controlled trial (N = 354). Participants were assigned to complete a MC or reflection (control) exercise prior to filling out a melanoma risk calculator. Participants were then asked whether they wanted to learn their melanoma risk, and how much information they would like to know., Results: Chi-Square tests revealed that MC decreased melanoma risk information avoidance compared to the reflection activity (12% vs. 23.4%) but did not make participants more likely seek additional information., Conclusion: MC is a brief, engaging, and effective strategy for reducing health information avoidance that could prove useful in medical settings., (© Society of Behavioral Medicine 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: To explore whether robotic lobectomy (RL) is superior to video-assisted lobectomy (VAL) in terms of short-term outcomes in patients with pulmonary neoplasms., Methods: From January 30, 2019 to February 28, 2022, a series of consecutive minimally invasive lobectomies were performed for patients with pulmonary neoplasms. Perioperative outcomes such as operation time, blood loss, dissected lymph nodes (LNs), surgical complications, postoperative pain control, length of postoperative stay in hospital, and total cost of hospitalization were compared., Results: A total of 336 cases including 173 RLs and 163 VALs were enrolled. Baseline characteristics were comparable between groups. RLs were associated with shorter operation time (median [interquadrant range, IQR], 107 min [90-130] vs. 120 min [100-149], p < 0.001), less blood loss (median [IQR], 50 mL [30-60] vs. 50 mL [50-80], p = 0.02), and lower blood transfusion rate (3.5% vs. 9.8%, p = 0.02) compared with VALs. More LNs were harvested by the robotic approach (median [IQR], 29 [20-41] vs. 22 [15-45], p = 0.04). The incidences of conversion, major postoperative complications, extra analgesic usage, and postoperative length of stay were all comparable between the RL and VAL groups. As predicted, the total cost of hospitalization was greater in the RL group (median [IQR], $16728.35 [15682.16-17872.15] vs. $10713.47 [9662.13-11742.15], p < 0.001)., Conclusion: RL improved surgical efficacy with shortened operative time, less blood loss, and more thorough LN dissection compared with VAL, compromised by higher cost., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Our study aimed to compare the short-term outcomes between robot-assisted segmentectomy (RAS) and video-assisted segmentectomy (VAS) for small pulmonary nodules., Methods: The study included of 299 segmentectomies (132 RAS and 167 VAS procedures) for small pulmonary nodules between June 2018 and November 2021. The patients were divided into two groups: the RAS group and the VAS group. Propensity score-matching (PSM) analysis was performed to minimize bias. A logistic regression model was performed to identify the independent risk factors associated with complications., Results: Before PSM, the following clinical variables were not balanced: age (P = 0.004), tumor size (P < 0.001), forced expiratory volume for 1 s (FEV1), and FEV1 percentage (P < 0.001). The patients with RAS had a shorter operative time (P = 0.014), less blood loss, a shorter postoperative hospital stay, less use of strong opioids, less drainage on postoperative day 1, and less postoperative total drainage, but more cost (all P < 0.001). Conversion to open surgery was performed for two patients in the VAS group but none in the RAS group. After PSM, 53 pairs were successfully matched. The data again suggested that the patients with RAS had less blood loss, a shorter postoperative hospital stay, and less use of strong opioids, but more cost (all P < 0.001). The operation time also was shorter in the RAS group, with a borderline statistically significant P value (0.053)., Conclusions: In our study, RAS had better short-term outcomes than VAS, indicating a safer and more efficient technique than VAS., (© 2023. Society of Surgical Oncology.)

In this study, a novel pressure-induced supercritical phase nucleation method is proposed to synthesize monolayer MoS 2 films, which is promoter free and can avoid contamination of films derived from these heterogeneous promoters in most of the existing techniques. The low-crystallinity and size-controlled MoO 2 (acac) 2 particles are recrystallized on the substrate via the pressure-sensitive solvent capacity of supercritical CO 2 and these particles are used as growth sites. The size of single-crystal MoS 2 on the substrate is found to be dependent on the wetting area of the pyrolyzed precursor droplets (MoO 2 ) on the surface, and the formation of continuous films with high coverage is mainly controlled by the coalescence of MoO 2 droplets. It is enhanced by the increase of the nucleation site density, which can be adjusted by the supersaturation of the supercritical fluid solution. Our findings pave a new way for the controllable growth of MoS 2 and other two-dimensional materials and provide sufficient and valuable evidence for vapor-liquid-solid growth.

We identified the prognostic factors of resected stage IA non-small cell lung cancer (NSCLC) and developed a nomogram, with purpose of defining the high-risk population who may need closer follow-up or more intensive care. Eligible stage IA NSCLC cases from the Surveillance, Epidemiology, and End Results (SEER) database and the Sun Yat-sen University Cancer Center (SYSUCC) were included. Stage IB NSCLCs were also included for evaluating the risk stratification efficacy. Cancer specific survival (CSS) was compared between groups. Statistically significant factors from multivariate analysis were entered into the nomogram. The performance of the nomogram was evaluated by concordance index (C-index) and calibration plots. A total of 23,112 NSCLC cases (SEER stage IA training cohort, N=7,777; SEER stage IA validation cohort, N=7,776; SEER stage IB cohort, N=7,559) from the SEER database were included. 1,304 NSCLC cases (SYSUCC stage IA validation cohort, N=684; SYSUCC stage IB cohort, N=620) from the SYSUCC were also included. Younger age, female, lobectomy, well differentiated, smaller size and more examined lymph nodes were identified as favorable prognostic factors. A nomogram was established. The C-index was 0.68 (95%CI, 0.67-0.69), 0.66 (95% CI, 0.64-0.68) and 0.66 (95% CI, 0.61-0.71) for the SEER training cohort, SEER validation cohort and SYSUCC validation cohort. A risk classification system was constructed to stratify stage IA NSCLC into low-risk subgroup and high-risk subgroup. The CSS curves of these two subgroups showed statistically significant distinctions. This nomogram delivered a prognostic prediction for stage IA NSCLC and may aid individual clinical practice., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Endophytes and their elicitors can all be utilized in regulating crop biochemical qualities. However, living endophytes and their derived elicitors are always applied separately; little is known about the similarities and differences of their effects. To increase the efficiency of this system when applied in practice, the present work profiled simultaneously the metabolomes in grape cells exposed to endophytic fungi (EF) and their corresponding fungal extracts (CFE). As expected, grape cells exposed separately to different fungi, or to different fungi derived extracts, each exhibited different modifications of metabolite patterns. The metabolic profiles of certain EF- and CFE-exposed grape cells were also differently influenced to certain degrees, owing to the presence of differentially responding metabolites (DRMs). However, the detected majority proportions of coordinately responding metabolites (CRMs) in both the EF- and the CFE-exposed grape cells, as well as the significantly influenced metabolites (SIMs) which are specific to certain fungal strains, clearly indicate coordinative changes in metabolites in grape cells exposed to EF and CFEs. The coordinative changes in metabolites in EF- and CFE-treated grape cells appeared to be fungal strain-dependent. Notably, several of those fungal strain-specific CRMs and DRMs are metabolites and belong to amino acids, lipids, organic acids, phenolic acids, flavonoids, and others, which are major contributors to the biochemistry and sensory qualities of grapes and wines. This research clarifies the detailed responses of metabolites in grape cells exposed to EF and CFEs. It also demonstrates how endophytes can be selectively used in the form of extracts to produce functions as CRMs of the living fungus with increased eco-safety, or separately applied to the living microbes or elicitors to emphasize those effects related to their specifically initiated SIMs and DRMs.

Background: To investigate the impact of station 3A lymph node dissection (LND) on overall survival (OS) and disease-free survival (DFS) in completely resected right-side non-small-cell lung cancer (NSCLC) patients., Methods: A total of 1661 cases with completely resected right-side NSCLC were included. Propensity score matching (PSM) was performed to minimize selection bias, and a logistic regression model was conducted to investigate the risk factors associated with station 3A lymph node metastasis (LNM). The Kaplan-Meier method and Cox proportional hazards model were used to evaluate the impact of station 3A LND on survival., Results: For the entire cohort, 503 patients (30.3%) underwent station 3A LND. Of those, 11.3% (57/503) presented station 3A LNM. Univariate and multivariate logistic analyses showed that station 10 LNM, tumor location, and the number of resected lymph nodes were independent risk factors associated with station 3A LNM. Before PSM, patients with station 3A LND had worse 5-year OS (p = 0.002) and DFS (p = 0.011), and more drainage on postoperative day 1 (p = 0.041) than those without. After PSM, however, station 3A LND was not associated with the 5-year OS (65.7% vs. 63.6%, p = 0.432) or DFS (57.4% vs. 56.0%, p = 0.437). The multivariate analysis further confirmed that station 3A LND was not a prognostic factor (OS, p = 0.361; DFS, p = 0.447)., Conclusions: Station 3A LND could not improve long-term outcomes and it was unnecessary to dissect station 3A lymph nodes during surgery of right-side NSCLC., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: The benefit of adjuvant chemotherapy (ACT) in pathological T2N0M0 non-small-cell lung cancer (NSCLC) patients is not clear., Methods: One thousand and fifty pathological T2N0M0 NSCLC patients were included and divided into two groups: with and without ACT. A propensity score matching analysis was carried out to minimize selection bias. The significance of ACT in high-risk patients was further analyzed. The Kaplan-Meier method and Cox proportional hazards model were used to assess the impact of ACT on the overall survival (OS), disease-free survival (DFS), and cancer-specific survival., Results: For the entire cohort, 31.9% (335/1050) of patients received ACT. After propensity score matching, 325 pairs of patients were matched. OS and DFS were comparable between groups in the original or matched cohort, which was confirmed by the multivariate analysis (all P > 0.05). In high-risk patients, the data suggest that ACT could improve OS and DFS only in patients with tumours >4 cm (OS: P = 0.003; DFS: P = 0.013). ACT could significantly improve the 5-year OS in patients with wild-type epidermal growth factor receptor (EGFR) (P = 0.022). ACT, however, could not improve cancer-specific survival in any subgroup, including patients with tumours >4 cm or wild-type EGFR (all P > 0.05). For patients with other high-risk factors, ACT failed to benefit patients in long-term outcomes., Conclusions: In resected pT2N0M0 NSCLC patients, those with tumours >4 cm and wild-type EGFR are real high-risk patients and could gain survival benefit from ACT. Further prospective study is needed to confirm the definition., Competing Interests: Disclosure None declared., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Nasopharyngeal carcinoma (NPC) is a malignant tumor highly prevalent in Southeast Asia. The distant metastasis and disease recurrence are still unsolved clinical problems. In recent years, traditional Chinese medicine (TCM) monomers have become significantly attractive due to their advantages. Using high throughput drug sensitivity screening, we identified gambogic acid (GA) as a common TCM monomer displaying multiple anti-NPC effects. GA could effectively inhibit the proliferation of low differentiated cells and highly metastatic cells in NPC via inducing apoptosis and G2/M cell cycle arrest. In addition, GA obviously repressed the abilities of cell clone, migration, invasion, angiogenesis and represented satisfied synergistic effects combined with chemotherapy. Importantly, we found the elevated immune checkpoint CD47 stimulated after chemotherapy was dramatically impaired by GA treatment. Mechanically, the network pharmacology analyses unraveled that the oncogenic signaling pathways including STATs were rewired by GA treatment. Taken together, our study reveals a molecular basis and provides a rationale for GA application as the treatment regime in NPC therapy in future., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: To study the correlation between CT imaging features of acceleration and deceleration brain injury and injury degree., Methods: A total of 299 cases with acceleration and deceleration brain injury were collected and divided into acceleration brain injury group and deceleration brain injury group according to the injury mechanism. Subarachnoid hemorrhage (SAH) and Glasgow coma scale (GCS), combined with skull fracture, epidural hematoma (EDH), subdural hematoma (SDH) and brain contusion on the same and opposite sides of the stress point were selected as the screening indexes. χ 2 test was used for primary screening, and binary logistic regression analysis was used for secondary screening. The indexes with the strongest correlation in acceleration and deceleration injury mechanism were selected., Results: χ 2 test showed that skull fracture and EDH on the same side of the stress point; EDH, SDH and brain contusion on the opposite of the stress point; SAH, GCS were correlated with acceleration and deceleration injury ( P <0.05). According to binary logistic regression analysis, the odds ratio (OR) of EDH on the same side of the stress point was 2.697, the OR of brain contusion on the opposite of the stress point was 0.043 and the OR of GCS was 0.238, suggesting there was statistically significant ( P <0.05)., Conclusions: EDH on the same side of the stress point, brain contusion on the opposite of the stress point and GCS can be used as key indicators to distinguish acceleration and deceleration injury mechanism. In addition, skull fracture on the same side of the stress point, EDH and SDH on the opposite of the stress point and SAH were relatively weak indicators in distinguishing acceleration and deceleration injury mechanism.

Objective: To retrospectively analyze the data of Chinese patients with newly diagnosed acute promyelocytic leukemia (APL) to preliminarily discuss the clinical and cytogenetic characteristics. Methods: From February 2004 to June 2020, patients with newly diagnosed APL aged ≥ 15 years who were admitted to the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College were chosen. Clinical and laboratory features were retrospectively analyzed. Results: A total of 790 cases were included, with a male to female ratio of 1.22. The median age of the patients was 41 (15-76) years. Patients aged between 20 and 59 predominated, with 632 patients (80%) of 790 patients classified as low and intermediate risk and 158 patients (20%) of 790 patients classified as high risk. The white blood cell, platelet, and hemoglobin levels at diagnosis were 2.3 (0.1-176.1) ×10(9)/L, 29.5 (2.0-1220.8) ×10(9)/L, and 89 (15-169) g/L, respectively, and 4.8% of patients were complicated with psoriasis. The long-form type of PML-RARα was most commonly seen in APL, accounting for 58%. Both APTT extension (10.3%) and creatinine>14 mg/L (1%) are rarely seen in patients at diagnosis. Cytogenetics was performed in 715 patients with newly diagnosed APL. t (15;17) with additional chromosomal abnormalities were found in 155 patients, accounting for 21.7%; among which, +8 was most frequently seen. A complex karyotype was found in 64 (9.0%) patients. Next-generation sequencing was performed in 178 patients, and 113 mutated genes were discovered; 75 genes had an incidence rate>1%. FLT3 was the most frequently seen, which accounted for 44.9%, and 20.8% of the 178 patients present with FLT3-ITD. Conclusions: Patients aged 20-59 years are the most common group with newly diagnosed APL. No obvious difference was found in the ratio of males to females. In terms of risk stratification, patients divided into low and intermediate risk predominate. t (15;17) with additional chromosomal abnormalities accounted for 21% of 715 patients, in which +8 was most commonly seen. The long-form subtype was most frequently seen in PML-RARα-positive patients, and FLT3 was most commonly seen in the mutation spectrum of APL.

Hexagonal boron nitrides (hBNs) have a very high luminescence efficiency and are promising materials for deep-UV emitters. Although intense deep-UV emissions have been recorded in various forms of hBN excited by photons or energetic electrons, information on the electronic structure of the conduction band has been derived mainly from theoretical works. Therefore, there is a lack of high-resolution absorption data in the far-UV region. In this study, the far-UV absorption spectra of chemical-vapor-deposition-grown mono- and multilayer hBNs were recorded at 10 and 298 K. In addition to the previously reported band at 6.10 eV, two absorption bands at 6.82 and 8.86 eV were observed for the first time in thin-film hBN. Furthermore, excitation of the hBN thin film samples with 6.89-eV photons revealed intense emission peaks at 6.10 (mono) and 5.98 (multi) eV with a bandwidth of ∼0.7 eV. Comparing the absorption and photoluminescence data, we believe that both direct and indirect transitions occur in the radiative processes., 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 © 2022 Elsevier B.V. All rights reserved.)

Background: Early diagnosis and classification of infections increase the cure rate while decreasing complications, which is significant for severe infections, especially for war surgery. However, traditional methods rely on laborious operations and bulky devices. On the other hand, point-of-care (POC) methods suffer from limited robustness and accuracy. Therefore, it is of urgent demand to develop POC devices for rapid and accurate diagnosis of infections to fulfill on-site militarized requirements., Methods: We developed a wave-shaped microfluidic chip (WMC) assisted multiplexed detection platform (WMC-MDP). WMC-MDP reduces detection time and improves repeatability through premixing of the samples and reaction of the reagents. We further combined the detection platform with the streptavidin-biotin (SA-B) amplified system to enhance the sensitivity while using chemiluminescence (CL) intensity as signal readout. We realized simultaneous detection of C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) on the detection platform and evaluated the sensitivity, linear range, selectivity, and repeatability. Finally, we finished detecting 15 samples from volunteers and compared the results with commercial ELISA kits., Results: Detection of CRP, PCT, and IL-6 exhibited good linear relationships between CL intensities and concentrations in the range of 1.25-40 μg/ml, 0.4-12.8 ng/ml, and 50-1600 pg/ml, respectively. The limit of detection of CRP, PCT, and IL-6 were 0.54 μg/ml, 0.11 ng/ml, and 16.25 pg/ml, respectively. WMC-MDP is capable of good adequate selectivity and repeatability. The whole detection procedure takes only 22 min that meets the requirements of a POC device. Results of 15 samples from volunteers were consistent with the results detected by commercial ELISA kits., Conclusions: WMC-MDP allows simultaneous, rapid, and sensitive detection of CRP, PCT, and IL-6 with satisfactory selectivity and repeatability, requiring minimal manipulation. However, WMC-MDP takes advantage of being a microfluidic device showing the coefficients of variation less than 10% enabling WMC-MDP to be a type of point-of-care testing (POCT). Therefore, WMC-MDP provides a promising alternative to POCT of multiple biomarkers. We believe the practical application of WMC-MDP in militarized fields will revolutionize infection diagnosis for soldiers., (© 2022. The Author(s).)

Using a carboxylic acid linker, this work achieved the epitaxially coordinated assembly of a Ag-S layer into a three-dimensional semi-conductive framework, with high thermal stability, as well as an interesting temperature-dependent luminescence response. This work provides a new avenue to prepare semi-conductive metal-chalcogenide layer-based materials in electricity-related applications.

Abstract: In the field of forensic medicine, diagnosis of sudden cardiac death is limited by subjective factors and manual measurement methods, so some parameters may have estimation deviation or measurement deviation. As postmortem CT imaging plays a more and more important role in the appraisal of cause of death and cardiopathology research, the application of deep learning such as artificial intelligence technology to analyze vast amounts of cardiac imaging data has provided a possibility for forensic identification and scientific research workers to conduct precise diagnosis and quantitative analysis of cardiac diseases. This article summarizes the main researches on deep learning in the field of cardiac imaging in recent years, and proposes a feasible development direction for the application of deep learning in the virtual anatomy of sudden cardiac death at present., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

Background: Visceral pleural invasion (VPI) with PL1 or PL2 increases the T classification from T1 to T2 in non-small cell lung cancers (NSCLCs) ≤ 3 cm. We proposed a modified T classification based on VPI to guide adjuvant therapy., Research Question: Is it reasonable to upstage PL1-positive cases from T1 to T2 for NSCLCs ≤ 3 cm?, Study Design and Methods: In total, 1,055 patients with resected NSCLC were retrospectively included. Tumor sections were restained with hematoxylin and eosin stain and Victoria blue elastic stain for the elastic layer. Disease-free survival (DFS) and overall survival (OS) were calculated by the Kaplan-Meier method. Subgroup analysis and a Cox proportional hazards model were used to further determine the impact of VPI on survival., Results: The extent of VPI was diagnosed as PL0 in 824 patients, PL1 in 133 patients, and PL2 in 98 patients. The 5-year DFS rates of patients with PL0, PL1, and PL2 were 62.6%, 60.2%, and 28.8% (P < .01), whereas the corresponding 5-year OS rates were 78.6%, 74.4%, and 50.0% (P < .01), respectively. As predicted, the DFS and OS of patients with PL2 were much worse than those of patients with PL0 (P < .01) and PL1 (P < .01). However, both the DFS and OS of patients with PL0 and PL1 were comparable (DFS: P = .198; OS: P = .150). For node-negative cases, the DFS and OS of patients with PL0 and PL1 were also comparable (DFS: P = .468; OS: P = .388), but patients with PL2 had much worse DFS and OS than patients with PL0 (P < .01) and PL1 (P < .01). Multivariable analyses suggested that PL2, together with node positivity and poor cell differentiation, was an independent adverse prognostic factor., Interpretation: In NSCLCs ≤ 3 cm, tumors with PL1 should remain defined as T1, not T2. Overtreatment by adjuvant chemotherapy in node-negative NSCLCs ≤ 3 cm might be avoided in PL1 cases., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Abstract: Among many factors that affect postmortem interval （PMI）, temperature is undoubtedly the most important factor, but simply considering temperature in estimation of PMI has limitations. Accumulated degree days （ADD） is an important indicator related to biological growth and development, which considers two major variables, environmental temperature and elapsed time. Therefore, the establishment of mathematical model of ADD and some evaluation indicators to estimate PMI, is obviously better than single temperature variable. This article briefly describes the research history of ADD, its application in PMI estimation, and the problems it faces, to provide reference for the further development of ADD to improve the accuracy of PMI estimation., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

Aims: Growing evidence suggests that vascular endothelial growth factor (VEGF) may be involved in the neuronal mechanisms underlying both depression aetiology and the response to ketamine treatments. The aim of this study was to examine whether changes in plasma VEGF levels are associated with the antidepressant effects of repeated ketamine infusions in patients with depression., Methods: Ninety-six patients with depression were enrolled and received six ketamine infusions during a 12-day period. Depressive symptom severity and plasma VEGF levels were measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) and an enzyme-linked immunosorbent assay (ELISA) respectively, at baseline, 13 days and 26 days., Results: Despite a significant improvement in MADRS scores after patients received six ketamine infusions ( p  < 0.001), no changes in plasma VEGF levels were observed at 13 days when compared with baseline. Moreover, no significant difference in plasma VEGF levels at baseline and 13 days was found between ketamine responders and nonresponders. No association was found between the antidepressant effects of repeated ketamine treatments and plasma VEGF levels., Conclusion: This study indicated that VEGF may not be a potential predictor of antidepressant response to repeated intravenous administration of ketamine in patients with depression., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

Background: We aim to assess the learning curve of robotic portal lobectomy with four arms (RPL-4) in patients with pulmonary neoplasms using prospectively collected data., Methods: Data from 100 consecutive cases with lung neoplasms undergoing RPL-4 were prospectively accumulated into a database between June 2018 and August 2019. The Da Vinci Si system was used to perform RPL-4. Regression curves of cumulative sum analysis (CUSUM) and risk-adjusted CUSUM (RA-CUSUM) were fit to identify different phases of the learning curve. Clinical indicators and patient characteristics were compared between different phases., Results: The mean operative time, console time, and docking time for the entire cohort were 130.6 ± 53.8, 95.5 ± 52.3, and 6.4 ± 3.0 min, respectively. Based on CUSUM analysis of console time, the surgical experience can be divided into three different phases: 1-10 cases (learning phase), 11-51 cases (plateau phase), and >51 cases (mastery phase). RA-CUSUM analysis revealed that experience based on 56 cases was required to truly master this technique. Total operative time (p < 0.001), console time (p < 0.001), and docking time (p = 0.026) were reduced as experience increased. However, other indicators were not significantly different among these three phases., Conclusions: The RPL-4 learning curve can be divided into three phases. Ten cases were required to pass the learning curve, but the mastery of RPL-4 for satisfactory surgical outcomes requires experience with at least 56 cases., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Major pathologic response (MPR) is mainly focused on residual viable tumor in the tumor bed regardless of lymph node. Herein, we investigated the predictive value of MPR and node status on survival in nonsmall-cell lung cancer (NSCLC) patients receiving neoadjuvant chemotherapy (NAC) and surgery., Methods: A total of 194 eligible cases were included. Tumor pathologic response and node status were assessed. Based on these evaluations, patients were divided into the MPR group and the non-MPR group, the nodal downstaging (ND) group and non-ND group. Furthermore, patients were assigned into four subgroups (MPR + ND, MPR + non-ND, non-MPR + ND, and non-MPR + non-ND). Overall survival (OS) and disease-free survival (DFS) were compared between groups. Multivariate analyses were performed to identify prognostic factors., Results: MPR was identified in 32 patients and ND was present in 108 patients. OS and DFS were better in the MPR group than in the non-MPR group, but with no statistical significance (OS, p = 0.158; DFS, p = 0.126). The ND group had better OS than the non-ND group (p = 0.031). However, the DFS between these two groups was comparable (p = 0.103). Further analyses suggested that both OS and DFS were better in the MPR + ND group than in the non-MPR + non-ND group (OS, p = 0.017; DFS, p = 0.029). Multivariate analyses confirmed that MPR + ND was an independent favorable predictor., Conclusions: MPR combined with ND could improve the predictive value on survival in NSCLC patients receiving NAC., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Nasopharyngeal carcinoma (NPC) is a malignant tumor in southern China, and nano Traditional Chinese Medicine (TCM) represents great potential to cancer therapy. To predict the potential targets and mechanism of polyphyllin II against NPC and explore its possibility for the future nano-pharmaceutics of Chinese medicine monomers, network pharmacology was included in the present study. Totally, ninety-four common potential targets for NPC and polyphyllin II were discovered. Gene Ontology (GO) function enrichment analysis showed that biological processes and functions mainly concentrated on apoptotic process, protein phosphorylation, cytosol, protein binding, and ATP binding. In addition, the anti-NPC effects of polyphyllin II mainly involved in the pathways related to cancer, especially in the PI3K-Akt signaling indicated by the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The "drug-target-disease" network diagram indicated that the key genes were SRC, MAPK1, MAPK14, and AKT1. Taken together, this study revealed the potential drug targets and underlying mechanisms of polyphyllin II against NPC through modern network pharmacology, which provided a certain theoretical basis for the future nano TCM research., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Meng-Zhe Yang et al.)

Parathyroid cysts (PCs) are rare, benign, cystic lesions, and PCs that occur in the mediastinum (mediastinal parathyroid cysts [MPCs]) are even more rare. Surgical resection is recommended as the first choice of treatment for MPCs. Sternotomy, thoracotomy, and thoracoscopic approaches are the most common methods for resection of MPCs. Herein, we report a case of robotic right portal minimally invasive resection of a giant nonfunctional MPC in the right anterosuperior mediastinum., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

As all- trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO-based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA-anthracycline for low-/intermediate-risk patients, or ATRA-ATO-anthracycline versus ATRA-anthracycline-cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of -5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI -0.07 to 6.97), confirming noninferiority ( P < 0.001). Using the Kaplan-Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups ( P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA-chemotherapy (https://www.clinicaltrials.gov/, NCT01987297)., Competing Interests: The authors declare no competing interest.

Bortezomib is a novel proteasome inhibitor, which has been successfully used to treat mantle cell lymphoma and multiple myeloma. However, the direct effects of bortezomib on acute promyelocytic leukaemia (APL) have not been fully investigated. In the present study, the WST-8 assay, western blotting, flow cytometry, monodansylcadaverine staining and transmission electron microscopy were performed. It was demonstrated that bortezomib treatment induced a time- and dose-dependent decrease in the viability of NB4 cells. Bortezomib treatment induced cell apoptosis in NB4 cells, as assessed by Annexin V/propidium iodide analysis, and the detection of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase, Bax and Bcl-2 expression. Furthermore, bortezomib treatment induced autophagy in NB4 cells, as indicated by autophagosome formation, p62 degradation, LC3-I to LC3-II conversion and formation of acidic autophagic vacuoles. Notably, autophagy induced by bortezomib was initiated prior to apoptosis. Inhibition of autophagy by knocking down Beclin-1 expression increased bortezomib-induced apoptosis in NB4 cells. Therefore, the present study revealed that the combination of bortezomib and autophagy inhibition may be a potential treatment strategy for APL., (Copyright: © Jiang et al.)

Abstract: Objective To determine the purine adenylate [adenosine triphosphate （ATP）, adenosine diphosphate （ADP）, adenosine monophosphate （AMP）] content in the muscles of both hind limbs of rats at different postmortem interval （PMI）, calculate the changes in the total adenine nucleotide （TAN） content and the adenylic-acid energy charge （AEC）, and explore their relationship with PMI. Methods Healthy rats were sacrificed by cervical dislocation and kept at 20 ℃. The muscles of their hind limbs were extracted at 0, 24, 48, 72, 96, 120, 144, and 168 h after death. Reversed-phase high performance liquid chromatography was used to determine the content of purine adenylates, the TAN and AEC of the muscles of the both hind limbs were calculated, and the related regression equations of their relationship with PMI were established. Results Within 168 h of death of rats, the trend of ATP change was different from ADP, and the content of AMP continuously increased. The TAN value gradually increased with the extension of PMI, and the AEC showed a downward trend within 168 h after death. Among them, the patterns of AEC changes with PMI were obvious, the correlation coefficient was high （ R 2 =0.903）, and the curve fitting relationship was good; the fitting relationship between ATP, ADP, AMP, TAN and PMI was poor （ R 2 =0.198-0.754）. Conclusion The postmortem change patterns of AEC provide new research ideas for PMI estimation in the forensic field., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

Background: This study is the first to examine the association between plasma levels of brain-derived neurotrophic factor (BDNF) and the antisuicidal effects of repeated ketamine infusions in depressed patients with suicidal ideation., Methods: Fifty-seven depressed patients with suicidal ideation received six ketamine infusions (0.5 mg/kg) during a 12 days period. Suicidality was measured with the Scale for Suicidal Ideations (SSI-part 1), item 10 of the Montgomery-Åsberg Depression Rating Scale (MADRS), and item 3 of the Hamilton Depression Rating Scale (HAMD) at baseline, 1 day after the first infusion (1 day), 1 day after the sixth infusion (13 days), and at 2 weeks after the last infusion (26 days). Plasma levels of BDNF were measured by enzyme-linked immunosorbent assay at baseline, 13 days, and 26 days., Results: Overall, 46 (80.7%) depressed patients with suicidal ideation had an antisuicidal response at 13 days. Despite a significant reduction in suicidal symptoms over time, no changes in plasma levels of BDNF were found after ketamine treatment when compared with baseline. Correlation analysis showed that no significant association was observed between the plasma levels of BDNF and the changes in the severity of suicidal symptoms as measured by SSI-part 1, item 10 of the MADRS, or item 3 of the HAMD at 1 day, 13 days, and 26 days (all p  < 0.05)., Conclusion: Our results indicated that plasma levels of BDNF may not serve as a biomarker for determining the antisuicidal effects of six ketamine infusions in depressed patients with suicidal ideation., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Objective: The N-methyl-D-aspartate subtype glutamate receptor antagonist ketamine has rapid antidepressant and antisuicidal effects in treating treatment-resistant bipolar depression (TRBD). The neurocognitive effects of repeated ketamine infusions in TRBD are not known., Methods: Six intravenous infusions of ketamine (0.5 mg/kg over 40 min) were administered on a Monday-Wednesday-Friday schedule during a 12-day period on 16 patients with TRBD followed by a 2-week observational period. The assessment of neurocognitive function was conducted using the MATRICS Consensus Cognitive Battery at baseline, 13 and 26 days. Tasks were designed to test speed of processing, working memory, visual learning and verbal learning., Results: A significant improvement was found only in scores of speed of processing ( F = 9.9, p = 0.001) after a 2-week observational period, which was accounted for by the improvement of depression symptoms. There were no significant changes over time in terms of working memory, visual learning and verbal learning. Pearson correlation analysis showed that the improvement of depression symptoms through six ketamine infusions was greater among TRBD patients with lower working memory at baseline ( r = 0.54, p = 0.03). In multiple regression analysis, the significant correlation was still maintained (beta = 0.67, t = 2.2, p = 0.04)., Conclusion: This preliminary study indicated that six ketamine infusions were not harmful but were slightly beneficial for speed of processing in TRBD. However, this change was mainly accounted for the improvement of depression symptoms over time. Lower baseline working memory appears to be associated with greater antidepressant response after completion of six ketamine infusions in patients with TRBD., Competing Interests: The authors declare that they have no competing interests., (© 2020 Zheng et al.)

Endophytic fungi produce many novel bioactive metabolites that are directly used as drugs or that function as the precursor structures of other chemicals. The metabolic shaping of endophytes on grape cells was reported previously. However, there are no reports on the interactions and metabolic impact of endophyte symbiosis on in vitro vine leaves, which may be examined under well-controlled conditions that are more representative of the natural situation of endophytes within grapevines. The present study used an in vitro leaf method to establish endophyte symbiosis of grapevines and analyze the effects on the metabolic profiles of grape leaves from two different cultivars, 'Rose honey' (RH) and 'Cabernet sauvignon' (CS). The effects of endophytic fungi on the metabolic profiles of grape leaves exhibited host selectivity and fungal strain specificity. Most of the endophytic fungal strains introduced novel metabolites into the two varieties of grape leaves according to the contents of the detected metabolites and composition of metabolites. Strains RH49 and MDR36, with high or moderate symbiosis rates, triggered an increased response in terms of the detected metabolites, and the strains MDR1 and MDR33 suppressed the detected metabolites in CS and RH leaves despite having strong or moderate symbiosis ability. However, the strain RH12 significantly induced the production of novel metabolites in RH leaves due to its high symbiosis ability and suppression of metabolites in CS leaves., Competing Interests: The authors have declared that no competing interests exist.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA ZFPM2-AS1 promotes the tumorigenesis of renal cell cancer via targeting miR-137, by J.-G. Liu, H.-B. Wang, G. Wan, M.-Z. Yang, X.-J. Jiang, J.-Y. Yang, published in Eur Rev Med Pharmacol Sci 2019; 23 (13): 5675-5681-DOI: 10.26355/eurrev&#95;201907&#95;18304-PMID: 31298319" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18304.

Local pathogens can accumulate as asymptomatic endophytes, making it difficult to detect the impacts of invasive species as propagators of disease in the invaded range. We used the invasive plant Ageratina adenophora to assess such accumulation. We intensively collected foliar fungal endophytes and leaf spot pathogens of A. adenophora and co-occurring neighbours and performed an inoculation experiment to evaluate their pathogenicity and host range. Ageratina adenophora harboured diverse necrotrophic pathogens; its communities of endophytes and leaf spot pathogens were different in composition and shared only a small number of fungal species. In the pathogen communities of local plant hosts, 21% of the operational taxonomic units (OTUs), representing 50% of strains, also occurred as leaf spot pathogens and/or endophytes of A. adenophora. The local pathogen community was more similar to the endophytes than to the pathogens of A. adenophora. The inoculation experiment showed that local pathogens could infect A. adenophora leaves asymptomatically and that local plant hosts were susceptible to both A. adenophora endophytes and pathogens. Ageratina adenophora is a highly competent host for local pathogens, and its asymptomatic latent pathogens are fungi primarily shared with local neighbours. This poses challenges for understanding the long-term ecological consequences of plant invasion., (© 2020 The Authors. New Phytologist © 2020 New Phytologist Trust.)

Experimental and molecular epidemiological studies indicate important roles for adipose tissue or high-fat diet (HFD) in tumor growth and metastasis. Gastric cancer (GC) possesses a metastatic predilection for the adipocyte-rich peritoneum. However, the precise molecular relevance of HFD in the peritoneal metastasis of GC remains unclear. Here, we showed that HFD causes obvious fat accumulation and promotes peritoneal dissemination of GC in vivo. Peritoneum-derived adipocytes induces robust lipid droplet (LD) accumulation and fatty acid oxidation in GC cells through transcriptional upregulation of DGAT2 in a C/EBPα-dependent manner and prevents anoikis during peritoneal dissemination. Treatment of GC cells with FAs or coculture with adipocytes induces intracellular formation of LDs and production of NADPH to overcome oxidative stress in vitro. Importantly, overexpression of DGAT2 was identified as an independent predictor of poor survival that promotes lung and peritoneal metastasis of GC, and genetic or pharmacological inhibition of DGAT2, via disruption of lipid droplet formation in a lipid-rich environment, enhances the sensitivity of GC to anoikis in vitro and inhibits peritoneal metastasis in vivo. Overall, our findings highlight the notion that DGAT2 may be a promising therapeutic target in GC with peritoneal implantation and provide some evidence for uncovering the link between obesity and tumor metastasis., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To explore the treatment conditions of acid decalcified specimens and improve the poor quality of sections and unclear structure of hematoxylin-eosin (HE) staining caused by the change in pH in tooth and hard tissue after acid decalcification., Methods: A total of 20 cases of oral pathological specimens that contain hard tissues were decalcified and treated with routine treatment, concentrated ammonia water immersion treatment, and saturated lithium carbonate solution immersion treatment. The quality and HE staining effects of hard tissue sections treated with different methods were compared., Results: Compared with routine treatment, lithium carbonate saturated solution treatment showed complete sections. Hematoxylin is strongly stained, the nucleus is clear, and the cytoplasm is bright., Conclusions: Soaking acid decalcified specimens in lithium carbonate saturated solution before embedding in dehydration can neutralize the acidic environment of the tissue. The quality of sections and HE staining effect are improved and are suitable for the pretreatment of acid decalcified tissue samples of oral pathology.