NIR Absorbing Organic Chromophores Combination with NSAIDs for Remodeling of the Inflammatory Microenvironment to Amplify Tumor Ferroptosis-Photothermal Synergistic Therapy.

Photothermal therapy has emerged as a promising approach for cancer treatment, which can cause ferroptosis to enhance immunotherapeutic efficacy. However, excessively generated immunogenicity will induce serious inflammatory response syndrome, resulting in a discounted therapeutic effect. Herein, a kind of NIR absorption small organic chromophore nanoparticles (TTHM NPs) with high photothermal conversion efficiency (68.33%) is developed, which can induce mitochondria dysfunction, generate mitochondrial superoxide, and following ferroptosis. TTHM NPs-based photothermal therapy is combined with Sulfasalazine (SUZ), a kind of nonsteroidal anti-inflammatory drugs, to weaken inflammation and promote ferroptosis through suppressing glutamate/cystine (Glu/Cys) antiporter system Xc- (xCT). Additionally, the combination of SUZ with PTT can induce immunogenic cell death (ICD), followed by promoting the maturation of DCs and the attraction of CD8+ T cell, which will secrete IFN-γ and trigger self-amplified ferroptosis via inhibiting xCT and simulating Acyl-CoA synthetase long-chain family member 4 (ACSL4). Moreover, the in vivo results demonstrate that this combination therapy can suppress the expression of inflammatory factors, enhance dendritic cell activation, facilitate T-cell infiltration, and realize effective thermal elimination of primary tumors and distant tumors. In general, this work provides an excellent example of combined medication and stimulates new thinking about onco-therapy and inflammatory response.

18F-FDG PET/CT Radiomics-Based Multimodality Fusion Model for Preoperative Individualized Noninvasive Prediction of Peritoneal Metastasis in Advanced Gastric Cancer.

PURPOSE: This study was designed to develop and validate a machine learning-based, multimodality fusion (MMF) model using 18F-fluorodeoxyglucose (FDG) PET/CT radiomics and kernelled support tensor machine (KSTM), integrated with clinical factors and nuclear medicine experts' diagnoses to individually predict peritoneal metastasis (PM) in advanced gastric cancer (AGC). METHODS: A total of 167 patients receiving preoperative PET/CT and subsequent surgery were included between November 2006 and September 2020 and were divided into a training and testing cohort. The PM status was confirmed via laparoscopic exploration and postoperative pathology. The PET/CT signatures were constructed by classic radiomic, handcrafted-feature-based model and KSTM self-learning-based model. The clinical nomogram was constructed by independent risk factors for PM. Lastly, the PET/CT signatures, clinical nomogram, and experts' diagnoses were fused using evidential reasoning to establish the MMF model. RESULTS: The MMF model showed excellent performance in both cohorts (area under the curve [AUC] 94.16% and 90.84% in training and testing), and demonstrated better prediction accuracy than clinical nomogram or experts' diagnoses (net reclassification improvement p < 0.05). The MMF model also had satisfactory generalization ability, even in mucinous adenocarcinoma and signet ring cell carcinoma which have poor uptake of 18F-FDG (AUC 97.98% and 89.71% in training and testing). CONCLUSIONS: The 18F-FDG PET/CT radiomics-based MMF model may have significant clinical implications in predicting PM in AGC, revealing that it is necessary to combine the information from different modalities for comprehensive prediction of PM.

Survey of Heterodera glycines population abundance and virulence phenotypes during 2021-2022 in Heilongjiang Province.

Soybean cyst nematode (SCN), Heterodera glycines, poses a significant threat to global soybean production. Heilongjiang, the largest soybean-producing province in China, contributes over 40% to the country's total yield. This province has much longer history of SCN infestation. To assess the current situation in Heilongjiang, we conducted a survey to determine the SCN population density and virulence phenotypes during 2021-2022 and compared the data with a previous study in 2015. A total of 377 soil samples from 48 counties representing eleven major soybean-planting regions were collected. The prevalence of SCN increased from 55.4% in 2015 to 59% in the current survey. The population densities ranged from 80 to 26,700 eggs and juveniles per 100 cm3 of soil. Virulence phenotypes were evaluated for 60 representative SCN populations using the HG type test, revealing nine different HG types. The most common virulence phenotypes were HG types 7 and 0, accounting for 56.7% and 20% of all SCN populations, respectively. The prevalence of populations with a reproductive index (FI) greater than 10% on PI548316 increased from 64.5% in 2015 to 71.7%. However, the FI on the commonly used resistance sources PI 548402 (Peking) and PI 437654 remained low at 3.3%. These findings highlight the increasing prevalence and changing virulence phenotypes of SCN in Heilongjiang. They also emphasize the importance of rotating soybean varieties with different resistance sources and urgently identifying new sources of resistance to combat SCN.

High-Quality Nuclear Genome and Mitogenome of Bipolaris sorokiniana LK93, a Devastating Pathogen Causing Wheat Root Rot.

Bipolaris sorokiniana, one of the most devastating hemibiotrophic fungal pathogens, causes root rot, crown rot, leaf blotching, and black embryos of gramineous crops worldwide, posing a serious threat to global food security. However, the host-pathogen interaction mechanism between B. sorokiniana and wheat remains poorly understood. To facilitate related studies, we sequenced and assembled the genome of B. sorokiniana LK93. Nanopore long reads and next generation sequencing short reads were applied in the genome assembly, and the final 36.4-Mb genome assembly contains 16 contigs with the contig N50 of 2.3 Mb. Subsequently, we annotated 11,811 protein-coding genes. Of these, 10,620 were functional genes, 258 of which were identified as secretory proteins, including 211 predicted effectors. Additionally, the 111,581-bp mitogenome of LK93 was assembled and annotated. The LK93 genomes presented in this study will facilitate research in the B. sorokiniana-wheat pathosystem for better control of crop diseases. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Cancer Immunotherapy Based on Cell Membrane-Coated Nanocomposites Augmenting cGAS/STING Activation by Efferocytosis Blockade.

Innate immunity triggered by the cGAS/STING pathway has the potential to improve cancer immunotherapy. Previously, the authors reported that double-stranded DNA (dsDNA) released by dying tumor cells can trigger the cGAS/STING pathway. However, owing to efferocytosis, dying tumor cells are engulfed and cleared before the damaged dsDNA is released; hence, immunologic tolerance and immune escape occur. Herein, a cancer-cell-membrane biomimetic nanocomposites that exhibit tumor-immunotherapeutic effects are synthesized by augmenting the cGAS/STING pathway and suppressing efferocytosis. Once internalized by cancer cells, a combined chemo/chemodynamic therapy would be triggered, which damages their nuclear and mitochondrial DNA. Furthermore, the releasing Annexin A5 protein could inhibit efferocytosis effect and promote immunostimulatory secondary necrosis by preventing phosphatidylserine exposure, resulting in the burst release of dsDNA. These dsDNA fragments, as molecular patterns to immunogenic damage, escape from the cancer cells, activate the cGAS/STING pathway, enhance cross-presentation inside dendritic cells, and promote M1-polarization of tumor-associated macrophages. In vivo experiments suggest that the proposed nanocomposite could recruit cytotoxic T-cells and facilitate long-term immunological memory. Moreover, when combined with immune-checkpoint blockades, it could augment the immune response. Therefore, this novel biomimetic nanocomposite is a promising strategy for generating adaptive antitumor immune responses.

Persulfidation maintains cytosolic G6PDs activity through changing tetrameric structure and competing cysteine sulfur oxidation under salt stress in Arabidopsis and tomato.

Glucose-6-phosphate dehydrogenases (G6PDs) are essential regulators of cellular redox. Hydrogen sulfide (H2 S) is a small gasotransmitter that improves plant adaptation to stress; however, its role in regulating G6PD oligomerization to resist oxidative stress remains unknown in plants. Persulfidation of cytosolic G6PDs was analyzed by mass spectrometry (MS). The structural change model of AtG6PD6 homooligomer was built by chemical cross-linking coupled with mass spectrometry (CXMS). We isolated AtG6PD6C159A and SlG6PDCC155A transgenic lines to confirm the in vivo function of persulfidated sites with the g6pd5,6 background. Persulfidation occurs at Arabidopsis G6PD6 Cystine (Cys)159 and tomato G6PDC Cys155, leading to alterations of spatial distance between lysine (K)491-K475 from 42.0 Å to 10.3 Å within the G6PD tetramer. The structural alteration occurs in the structural NADP+ binding domain, which governs the stability of G6PD homooligomer. Persulfidation enhances G6PD oligomerization, thereby increasing substrate affinity. Under high salt stress, cytosolic G6PDs activity was inhibited due to oxidative modifications. Persulfidation protects these specific sites and prevents oxidative damage. In summary, H2 S-mediated persulfidation promotes cytosolic G6PD activity by altering homotetrameric structure. The cytosolic G6PD adaptive regulation with two kinds of protein modifications at the atomic and molecular levels is critical for the cellular stress response.

Safety and Efficacy of OGT-Assisted Overlap Oesophagojejunostomy Versus the Traditional Overlap Method in Laparoscopic Total Gastrectomy for Gastric/Gastroesophageal Junction (G/GEJ) Tumours.

INTRODUCTION: Overlap guiding tube (OGT)-assisted overlap oesophagojejunostomy (EJS), which was first designed and reported by our team, has shown feasibility. However, its safety and efficiency have not yet been compared with the conventional overlap approach. METHODS: We retrospectively analysed the data of 155 gastric/gastroesophageal junction (G/GEJ) cancer patients who underwent laparoscopic total gastrectomy by conventional (conventional group, n = 83) or OGT-assisted (OGT group, n = 72) overlap methods at Nanfang Hospital. The anastomotic efficiency and surgical outcomes were compared between the two groups. RESULTS: The success rate of inserting an anvil fork into the oesophageal lumen at the first attempt in the OGT group was much higher than in the conventional group (86.7% vs. 97.2%, P = 0.019). Consistently, the duration of EJS (P < 0.001) in the OGT group was significantly shorter than that in the conventional group. Operatively, there was one case in which oesophageal pseudocanals developed; another case was converted to thoracoscopic surgery in the conventional group, but there were no such cases in the OGT group. In terms of postoperative recovery, the OGT group was superior to the conventional group. The incidence of postoperative complications (28.9% vs. 20.8%, P = 0.247) and the classification of complication severity (P = 0.450) were milder in the OGT group, although the difference was not statistically significant. Notably, the conventional group had four cases (4.8%) of oesophagojejunal anastomotic leakage (EJAL) and one case (1.2%) of anastomotic stenosis. In the OGT group, two patients (2.8%) developed EJAL, but none developed anastomotic stenosis or anastomotic bleeding. Neither group had any cases of unplanned secondary surgery or perioperative deaths. CONCLUSIONS: The OGT-assisted method reduced the surgical difficulty of overlap EJS with good safety. This study provides new perspectives for optimizing EJS.

Impact of preoperative therapy on surgical outcomes of laparoscopic total gastrectomy for gastric/gastroesophageal junction cancer.

Objective: As laparoscopic surgery is widely applied for primarily treated gastric cancer (GC)/gastroesophageal junction cancer (GEJC) and gains many advantages, the feasibility of laparoscopic total gastrectomy (LTG) for GC/GEJC patients who have received preoperative therapy (PT) has come to the fore. This study aims to analyze the safety and feasibility of LTG after PT for GC/GEJC patients. Methods: We retrospectively analyzed the data of 511 patients with GC/GEJC undergoing LTG, of which 405 received LTG (LTG group) and 106 received PT+LTG (PT-LTG group) at Nanfang Hospital between June 2018 and September 2022. The surgical outcomes were compared between the two groups. Results: The surgical duration was significantly longer in the PT-LTG group (P<0.001), while the incidence of intraoperative complications (P=1.000), postoperative complications (LTG group vs. PT-LTG group: 26.2% vs. 23.6%, P=0.587), the classification of complication severity (P=0.271), and postoperative recovery was similar between two groups. Notably, the incidence of anastomotic complications of esophagojejunostomy was also comparable between the two groups (LTG group vs. PT-LTG group: 5.9% vs. 5.7%, P=0.918). The univariate and multivariate analysis confirmed that positive proximal margin [positive vs. negative: odds ratio (OR)=14.094, 95% confidence interval (95% CI): 2.639-75.260, P=0.002], rather than PT, has an impact on anastomotic complications after LTG (OR=0.945, 95% CI: 0.371-2.408, P=0.905). Conclusions: PT did not increase the surgical risk of LTG for GC/GEJC. Therefore, considering the positive effect of PT on long-term survival, the broader application of PT and LTG for GC/GEJC is supported by our findings.

First Report of Aphelenchoides besseyi Causing White Tip Disease of Rice in Heilongjiang Province of China.

Aphelenchoides besseyi is considered one of the most damaging plant parasitic nematodes to rice and can cause white tip disease. It was first discovered in Kyushu, Japan in 1915 and introduced into China from Japan in the 1940s. The disease is mainly found in rice-planting areas in South China (Zhu et al. 2016; Wang et al. 2017; Xu et al. 2019), causing yield losses of 30%-50% in irrigated rice (Wang et al. 2014). In summer 2021, rice plants displaying distortion and discoloration on new leaves, white tips on flag leaves, erect and shorter panicles, and fewer or less filled spikelets were observed in the rice field in Acheng district, Harbin city, Heilongjiang Province, China (13°32'33″S, 58°48'51″W). Plant samples with the typical symptoms of 'white tip' in the flag leaves were collected and transported to the laboratory for further pathogen identification. Nematodes were extracted from the leaves and panicles of diseased plants using Baermann funnel method, and the population density of nematode was an average of 57 individuals per sample (total 28 diseased samples). The main morphological characteristics of females (n = 20) and males (n = 15) were individually determined using a microscope (LEICA, DM2500). Female body was slender, and straight to ventrally curved when heat-relaxed, with a rounded cephalic region, the lateral field with four incisures, the excretory pore close to the anterior edge of the nerve ring, a narrow post-vulval sac and less than 1/3 the distance from the vulva to the anus, and a conoid tail with star-shaped mucro. Female measurements: body length = 724.6 (593.3 to 867.5) µm, stylet = 11.7 (10.9 to 12.5) µm, tail length = 39.4 (35.8 to 44.4) µm, a = 45.2 (38.6 to 51.0), b = 10.1 (9.4 to 10.7), c = 18.47 (14.7 to 21.4), and V = 71.1 (65.0 to 79.6). The body of male usually showed in a 'J' shape when relaxed, spicule length between 17.1 and 19.4 µm, and a conoid tail, with terminal mucro bearing two to four pointed processes. Male measurements: body length = 546.3 (521.7 to 587.6) µm, stylet = 11.9 (10.7 to 12.6) µm, tail length = 32.54 (29.53 to 34.35) µm, a = 37.7 (35.7 to 40.4), b = 8.7 (8.5 to 9.1), c = 17.8 (15.8 to19.4). The key morphological characteristics were coincident with the description of A. besseyi by Christie (1942), Ou et al. (2014) and Chen et al. (2020). DNA was extracted from six fresh nematodes, and the partial 18S-rRNA was amplified with a pair of primers 1813F/2646R (5'-CTGCGTGAGAGGTGAAAT-3'; 5'-GCTACCTTGTTACGACTTTT-3') (Holterman et al. 2006). PCR products of expected size were purified and sequenced. The newly obtained sequence (accession no. ON629604) was submitted to GenBank and displayed more than 99.5% identity with that of A. besseyi isolates (KT943536, KT454963, JQ957877). Additionally, the isolated nematodes were further confirmed using the species-specific primers Abess_11F/Abess_11R (5'-GTATTCAATCCCGCGACACT-3'; 5'-CATCCTGTTCGGGCATAGTT-3'), and the PCR amplification generated a 570 bp fragment which was specific to the 28S rDNA region of A. besseyi reported previously (Noronha et al. 2020). The pathogenicity test was confirmed in a pot assay. Approximately 2000 mixed-stage A. besseyi (juveniles, males and females) were obtained from the field-diseased rice plants, and ten-day-old rice seedlings (Japonica rice variety, Keyou 1) (n = 5) were inoculated with 400 nematodes per seedling and maintained in a greenhouse. During early growth stages (fifty days after inoculation), some young leaves of infected plants showed the chlorotic tips. Ninety days after inoculation, similar field symptoms (white tip on leaves) were observed on the aerial tissues of the inoculated plants, and an average of 237 A. besseyi were re-isolated from each plant. To the best of our knowledge, this is the first report of A. besseyi on rice plant in Heilongjiang Province of Northeast China. This finding indicates that A. besseyi could become a severe threat to rice production in Heilongjiang Province and contributes to the further inspection and prevention of white tip disease in rice-growing areas of Heilongjiang Province.

First Report of Trichotylenchus changlingensis infecting Maize in Shaanxi, China.

Maize (Zea mays L.) is one of the most important crops worldwide. In September 2020, five maize plants and soil samples were received from a farmer. The samples were collected from a maize field in Fugu County (N 39.02805, E 111.06723), Shaanxi Province, China. These maize plants had the symptoms of stunting or thinning. Soil nematodes were extracted from soils with modified Baermann funnel method for 48 h (Barker 1985). Trichotylenchus sp. were detected with populations ranging from 12 to 45 (in five soil samples) nematodes per 100 gram of fresh soil. Maize were planted in pots with soil samples containing Trichotylenchus sp. to propagate this plant-parasitic nematode at 20-28 °C in a greenhouse. After plants had grown for 60 days, active Trichotylenchus sp. were observed and picked under an anatomical lens (SZX16, Olympus, Tokyo, Japan) for an inoculation experiment. Freshly germinated maize (Limin 33) seeds were planted into paper pots with a sterilized mixture of soil and sand (4:1). Four plants were inoculated with approximately 2800 mixed-stage nematodes. The maize plants were allowed to grow under room conditions (15-20 °C) for two weeks and transferred to plastic pots (12 cm diameter × 10 cm deep) with the same soil mixture. After 30 days, all inoculated plants displayed the disease symptoms such as hypoplasia of fibrous roots and a hole at the base of the maize stem, but the Trichotylenchus sp. was not detected in maize roots and stems. The control plants did not exhibit any disease symptoms. The nematodes from the inoculated pots were identified by both morphological and molecular methods. The bodies of female and male were usually C-shaped when killed by hot water. The stylet was well developed with basal knobs. The posterior part of esophagus basal bulb did not overlap dorsally with the intestine. The female had a subcylindrical tail, but the male had a conical tail. The spicule of male was ventrally curved. The gubernaculum was well developed. Morphometric data based on females and males were presented as means (range). For female (n= 20): L = 1142.7 (1002.3 to 1313.4) µm, St = 26.5 (23.9 to 29.4) µm, a = 32.8 (27.4 to 38.7), b = 6.8 (6.0 to 7.9), c = 16.3 (14.9 to 19.4), c' = 2.7 (2.3 to 3.1), v = 51.3 (30.3 to 54.8), T = 70.1 (59.0 to 78.9) µm. For male (n= 20): L = 1093.3 (960.6 to 1183.7) µm, St = 24.3 (22.1 to 26.1) µm, a = 34.9 (31.1 to 39.1), b = 6.5 (5.6 to 7.4), c = 15.1 (13.6 to 16.7), c' = 3.6 (2.9 to 4.3), T = 72.5 (63.8 to 81.1) µm, SL = 28.8 (22.2 to 32.5) µm, GL = 11.5 (7.2 to 16.1) µm. The characteristics were coincident with the description of Trichotylenchus changlingensis (Guo et a., 2015). Genomic DNA was extracted from 10 nematodes, and PCR amplifications of the D2/D3 region of 28S rRNA were performed using universal primers D2A/D3B (Castillo et al. 2003), and that of the internal transcribed spacer (ITS)-rRNA region were amplified using universal primers TW81/AB28 (Amiri et al. 2002). A 780 bp amplicon of the 28S rRNA (GenBank accession no. OM276857.1) had 90.6% (Query Cover = 95%) identity with that of Tylenchorhynchus mediterraneus (KJ461557.1). Three ITS-rRNA region sequences (GenBank accession nos. OM294652.1, OM294653.1 and OM294654.1) were obtained, and the comparison revealed that sequences OM294652.1 and OM294653.1 had 98.90% (Query Cover = 100%) identity with the ITS-rRNA region sequence of T. changlingensis isolate (MH545694.1) from China, and OM294654.1 showed a 99.09 % (Query Cover = 99%) similarity to T. changlingensis sequence (MH545693.1). The morphological and molecular characterizations confirmed that the observed nematode was T. changlingensis, which is distributed in Heilongjiang, Jilin, Liaoning, Hebei, Gansu provinces and Inner Mongolia of China (Guo et al. 2020). To our knowledge, this is the first report of T. changlingensis infecting maize and causing disease in Shaanxi Province.

Development and Validation of a Deep Learning CT Signature to Predict Survival and Chemotherapy Benefit in Gastric Cancer: A Multicenter, Retrospective Study.

OBJECTIVE: We aimed to develop a deep learning-based signature to predict prognosis and benefit from adjuvant chemotherapy using preoperative computed tomography (CT) images. BACKGROUND: Current staging methods do not accurately predict the risk of disease relapse for patients with gastric cancer. METHODS: We proposed a novel deep neural network (S-net) to construct a CT signature for predicting disease-free survival (DFS) and overall survival in a training cohort of 457 patients, and independently tested it in an external validation cohort of 1158 patients. An integrated nomogram was constructed to demonstrate the added value of the imaging signature to established clinicopathologic factors for individualized survival prediction. Prediction performance was assessed with respect to discrimination, calibration, and clinical usefulness. RESULTS: The DeLIS was associated with DFS and overall survival in the overall validation cohort and among subgroups defined by clinicopathologic variables, and remained an independent prognostic factor in multivariable analysis (P< 0.001). Integrating the imaging signature and clinicopathologic factors improved prediction performance, with C-indices: 0.792-0.802 versus 0.719-0.724, and net reclassification improvement 10.1%-28.3%. Adjuvant chemotherapy was associated with improved DFS in stage II patients with high-DeLIS [hazard ratio = 0.362 (95% confidence interval 0.149-0.882)] and stage III patients with high- and intermediate-DeLIS [hazard ratio = 0.611 (0.442-0.843); 0.633 (0.433-0.925)]. On the other hand, adjuvant chemotherapy did not affect survival for patients with low-DeLIS, suggesting a predictive effect (Pinteraction = 0.048, 0.016 for DFS in stage II and III disease). CONCLUSIONS: The proposed imaging signature improved prognostic prediction and could help identify patients most likely to benefit from adjuvant chemotherapy in gastric cancer.

Survival analysis of elderly patients over 65 years old with stage II/III gastric cancer treated with adjuvant chemotherapy after laparoscopic D2 gastrectomy: a retrospective cohort study.

BACKGROUND: The benefits of adjuvant chemotherapy for elderly patients with gastric cancer (GC) remain unknown because elderly patients are underrepresented in most clinical trials. This study aimed to evaluate the effectiveness and complications of adjuvant chemotherapy in patients > 65 years of age after laparoscopic D2 gastrectomy. METHODS: This was a single-center retrospective cohort study of elderly patients (> 65 years) with stage II/III GC who underwent curative laparoscopic D2 gastrectomy with R0 resection between 2004 and 2018. The adjuvant chemotherapy regimens included monotherapy (oral capecitabine) and doublet chemotherapy (oral capecitabine plus intravenous oxaliplatin [XELOX] or intravenous oxaliplatin, leucovorin, and 5-fluorouracil [FOLFOX]). The data were retrieved from a prospectively registered database maintained at the Department of General Surgery in Nanfang Hospital, China. The patients were divided as surgery alone and surgery plus adjuvant chemotherapy (chemo group). The overall survival (OS), disease-free survival (DFS), chemotherapy duration, and toxicity were examined. RESULTS: There were 270 patients included: 169 and 101 in the surgery and chemo groups, respectively. There were 10 (10/101) and six (6/101) patients with grade 3+ non-hematological and hematological adverse events. The 1-/3-/5-year OS rates of the surgery group were 72.9%/51.8%/48.3%, compared with 90.1%/66.4%/48.6% for the chemo group (log-rank test: P = 0.018). For stage III patients, the 1-/3-/5-year OS rates of the surgery group were 83.7%/40.7%/28.7%, compared with 89.9%/61.2%/43.6% for the chemo group (log-rank test: P = 0.015). Adjuvant chemotherapy was significantly associated with higher OS (HR = 0.568, 95%CI: 0.357-0.903, P = 0.017) and DFS (HR = 0.511, 95%CI: 0.322-0.811, P = 0.004) in stage III patients. CONCLUSIONS: This study suggested that adjuvant chemotherapy significantly improves OS and DFS compared with surgery alone in elderly patients with stage III GC after D2 laparoscopic gastrectomy, with a tolerable adverse event profile.

Graphene oxide (GO)-based nanosheets with combined chemo/photothermal/photodynamic therapy to overcome gastric cancer (GC) paclitaxel resistance by reducing mitochondria-derived adenosine-triphosphate (ATP).

BACKGROUND: Paclitaxel (PTX) has been suggested to be a promising front-line drug for gastric cancer (GC), while P-glycoprotein (P-gp) could lead to drug resistance by pumping PTX out of GC cells. Consequently, it might be a hopeful way to combat drug resistance by inhibiting the out-pumping function of P-gp. RESULTS: In this study, we developed a drug delivery system incorporating PTX onto polyethylene glycol (PEG)-modified and oxidized sodium alginate (OSA)-functionalized graphene oxide (GO) nanosheets (NSs), called PTX@GO-PEG-OSA. Owing to pH/thermal-sensitive drug release properties, PTX@GO-PEG-OSA could induced more obvious antitumor effects on GC, compared to free PTX. With near infrared (NIR)-irradiation, PTX@GO-PEG-OSA could generate excessive reactive oxygen species (ROS), attack mitochondrial respiratory chain complex enzyme, reduce adenosine-triphosphate (ATP) supplement for P-gp, and effectively inhibit P-gp's efflux pump function. Since that, PTX@GO-PEG-OSA achieved better therapeutic effect on PTX-resistant GC without evident toxicity. CONCLUSIONS: In conclusion, PTX@GO-PEG-OSA could serve as a desirable strategy to reverse PTX's resistance, combined with chemo/photothermal/photodynamic therapy.

Enhanced recovery after surgery in laparoscopic distal gastrectomy: Protocol for a prospective single-arm clinical trial.

BACKGROUND: The enhanced recovery after surgery (ERAS) programme is feasible and effective in reducing the length of hospital stay, overall complication rates and medical costs when applied to cases involving colonic and rectal resections. However, a recent prospective, randomised, open, parallel-controlled trial (Chinese Laparoscopic Gastrointestinal Surgery Study-01 trial), initiated by our team, indicated that under conventional peri-operative management, the reduction of the post-operative hospital stay of laparoscopic distal gastrectomy (LDG) is quite limited compared with open gastrectomy. Thus, if we could provide valuable clinical evidence for demonstrating the efficacy of the ERAS programme for gastric cancer patients undergoing LDG, it would significantly enhance the peri-operative management of gastrectomy and benefit the patients. METHODS: In this prospective single-arm trial, patients who are 18-75 years of age with gastric adenocarcinoma diagnosed with cT1-4aN0-3M0 and expected to undergo curative resection through LDG, are considered eligible for this study. All participants underwent LDG with peri-operative management under the ERAS programme. The primary outcome measures included the post-operative hospital stays and rehabilitative rate of the post-operative day 4. The secondary outcome measures are morbidity and mortality (time frame: 30 days), post-operative recovery index (time frame: 30 days), post-operative pain intensity (time frame: 3 days) and the medical costs from surgery to discharge. CONCLUSION: With reasonable and scientific designing, the trial may be a great help to further discuss the benefit of ERAS programme and thus improving the peri-operative management of patients with gastrectomy.

Identification of Differentially Methylated miRNA Genes During Compatible and Incompatible Interactions Between Soybean and Soybean Cyst Nematode.

DNA methylation is a widespread epigenetic mark that affects gene expression and transposon mobility during plant development and stress responses. However, the role of DNA methylation in regulating the expression of microRNA (miRNA) genes remains largely unexplored. Here, we analyzed DNA methylation changes of miRNA genes using a pair of soybean (Glycine max) near-isogenic lines (NILs) differing in their response to soybean cyst nematode (SCN; Heterodera glycines). Differences in global DNA methylation levels over miRNA genes in response to SCN infection were observed between the isogenic lines. miRNA genes with significant changes in DNA methylation levels in the promoter and primary transcript-coding regions were detected in both lines. In the susceptible isogenic line (NIL-S), 82 differentially methylated miRNAs were identified in response to SCN infection whereas, in the resistant isogenic line (NIL-R), only 16 differentially methylated miRNAs were identified. Interestingly, gma-miR5032, gma-miR5043, gma-miR1520b, and gma-2107-ch16 showed opposite methylation patterns in the isogenic lines. In addition, the miRNA paralogs gma-miR5770a and gma-miR5770b showed hypermethylation and hypomethylation in NIL-S and NIL-R, respectively. Gene expression quantification of gma-miR5032, gma-miR5043, gma-miR1520b, and gma-miR5770a/b and their confirmed targets indicated a role of DNA methylation in regulating miRNA expression and, thus, their targets upon SCN infection. Furthermore, overexpression of these four miRNAs in NIL-S using transgenic hairy root system enhanced plant resistance to SCN to various degrees with a key role observed for miR5032. Together, our results provide new insights into the role of epigenetic mechanisms in controlling miRNA regulatory function during SCN-soybean interactions.[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Biodegradable hollow mesoporous organosilica nanotheranostics (HMON) for multi-mode imaging and mild photo-therapeutic-induced mitochondrial damage on gastric cancer.

BACKGROUND: CuS-modified hollow mesoporous organosilica nanoparticles (HMON@CuS) have been preferred as non-invasive treatment for cancer, as near infrared (NIR)-induced photo-thermal effect (PTT) and/or photo-dynamic effect (PDT) could increase cancer cells' apoptosis. However, the certain role of HMON@CuS-produced-PTT&PDT inducing gastric cancer (GC) cells' mitochondrial damage, remained unclear. Moreover, theranostic efficiency of HMON@CuS might be well improved by applying multi-modal imaging, which could offer an optimal therapeutic region and time window. Herein, new nanotheranostics agents were reported by Gd doped HMON decorated by CuS nanocrystals (called HMON@CuS/Gd). RESULTS: HMON@CuS/Gd exhibited appropriate size distribution, good biocompatibility, L-Glutathione (GSH) responsive degradable properties, high photo-thermal conversion efficiency (82.4%) and a simultaneous reactive oxygen species (ROS) generation effect. Meanwhile, HMON@CuS/Gd could efficiently enter GC cells, induce combined mild PTT (43-45 °C) and PDT under mild NIR power density (0.8 W/cm2). Surprisingly, it was found that PTT might not be the only factor of cell apoptosis, as ROS induced by PDT also seemed playing an essential role. The NIR-induced ROS could attack mitochondrial transmembrane potentials (MTPs), then promote mitochondrial reactive oxygen species (mitoROS) production. Meanwhile, mitochondrial damage dramatically changed the expression of anti-apoptotic protein (Bcl-2) and pro-apoptotic protein (Bax). Since that, mitochondrial permeability transition pore (mPTP) was opened, followed by inducing more cytochrome c (Cyto C) releasing from mitochondria into cytosol, and finally activated caspase-9/caspase-3-depended cell apoptosis pathway. Our in vivo data also showed that HMON@CuS/Gd exhibited good fluorescence (FL) imaging (wrapping fluorescent agent), enhanced T1 imaging under magnetic resonance imaging (MRI) and infrared thermal (IRT) imaging capacities. Guided by FL/MRI/IRT trimodal imaging, HMON@CuS/Gd could selectively cause mild photo-therapy at cancer region, efficiently inhibit the growth of GC cells without evident systemic toxicity in vivo. CONCLUSION: HMON@CuS/Gd could serve as a promising multifunctional nanotheranostic platform and as a cancer photo-therapy agent through inducing mitochondrial dysfunction on GC.

A deformable model for navigated laparoscopic gastrectomy based on finite elemental method.

Background: Accurate registration for surgical navigation of laparoscopic surgery is highly challenging due to vessel deformation. Here, we describe the design of a deformable model with improved matching accuracy by applying the finite element method (FEM).Material and methods: ANSYS software was used to simulate an FEM model of the vessel after pull-up based on laparoscopic gastrectomy requirements. The central line of the FEM model and the central line of the ground truth were drawn and compared. Based on the material and parameters determined from the animal experiment, a perigastric vessel FEM model of a gastric cancer patient was created, and its accuracy in a laparoscopic gastrectomy surgical scene was evaluated.Results: In the animal experiment, the FEM model created with Ogden foam material exhibited better results. The average distance between the two central lines was 6.5mm, and the average distance between their closest points was 3.8 mm. In the laparoscopic gastrectomy surgical scene, the FEM model and the true artery deformation demonstrated good coincidence.Conclusion: In this study, a deformable vessel model based on FEM was constructed using preoperative CT images to improve matching accuracy and to supply a reference for further research on deformation matching to facilitate laparoscopic gastrectomy navigation.

Impact of diabetes on prognosis of gastric cancer patients performed with gastrectomy.

OBJECTIVE: This study aimed to determine the impact of type 2 diabetes mellitus (T2DM) on clinical outcomes of gastric cancer (GC) patients and explore whether metformin use and good glycemic control could reverse it. METHODS: Clinicopathologic data of consecutive GC patients who underwent gastrectomy at Nanfang Hospital between October 2004 and December 2015 were included. Propensity score matching (PSM) was performed to balance the important factors of the disease status between non-T2DM and T2DM group. The last follow-up time was January 2019. RESULTS: A total of 1,692 eligible patients (1,621 non-T2DM vs. 71 T2DM) were included. After PSM, non-T2DM group (n=139) and T2DM group (n=71) were more balanced in baseline variables. The 5-year cancer-specific survival (CSS) rate in T2DM group (47.0%) was inferior to that in non-T2DM group (58.0%), but did not reach statistical significance [hazard ratio (HR)=1.319, 95% confidence interval (95% CI): 0.868-2.005, P=0.192]. While the 5-year progress-free survival (PFS) rate of T2DM group (40.6%) is significantly worse than that in non-T2DM group (56.3%) (HR=1.516, 95% CI: 1.004-2.290, P=0.045). Univariate and multivariate analyses showed that T2DM was an independent risk factor for PFS but not for CSS. In T2DM group, metformin use subgroup was associated with superior 5-year CSS and PFS in compared with non-metformin use subgroup, although the difference was not statistically significant (5-year CSS: 48.0%vs. 45.4%, HR=0.680, 95% CI: 0.352-1.313, P=0.246; 5-year PFS: 43.5%vs. 35.7%, HR=0.763, 95% CI: 0.400-1.454, P=0.406). The 5-year CSS rate was 47.5% in good glycemic control subgroup and 44.1% in poor glycemic control subgroup (HR=0.826, 95% CI: 0.398-1.713, P=0.605). And both two subgroups yielded a similar 5-year PFS rate (42.2%vs. 36.3%, HR=0.908, 95% CI: 0.441-1.871, P=0.792). CONCLUSIONS: DM promoted disease progress of GC after gastrectomy but had not yet led to the significant discrepancy of CSS. For GC patients with T2DM, metformin use was associated with superior survival but without statistical significance, while better glycemic control could not improve the prognosis.

A gastric cancer LncRNAs model for MSI and survival prediction based on support vector machine.

BACKGROUND: Recent studies have shown that long non-coding RNAs (lncRNAs) play a crucial role in the induction of cancer through epigenetic regulation, transcriptional regulation, post-transcriptional regulation and other aspects, thus participating in various biological processes such as cell proliferation, differentiation and apoptosis. As a new nova of anti-tumor therapy, immunotherapy has been shown to be effective in many tumors of which PD-1/PD-L1 monoclonal antibodies has been proofed to increase overall survival rate in advanced gastric cancer (GC). Microsatellite instability (MSI) was known as a biomarker of response to PD-1/PD-L1 monoclonal antibodies therapy. The aim of this study was to identify lncRNAs signatures able to classify MSI status and create a predictive model associated with MSI for GC patients. METHODS: Using the data of Stomach adenocarcinoma from The Cancer Genome Atlas (TCGA), we developed and validated a lncRNAs model for automatic MSI classification using a machine learning technology - support vector machine (SVM). The C-index was adopted to evaluate its accuracy. The prognostic values of overall survival (OS) and disease-free survival (DFS) were also assessed in this model. RESULTS: Using the SVM, a lncRNAs model was established consisting of 16 lncRNA features. In the training cohort with 94 GC patients, accuracy was confirmed with AUC 0.976 (95% CI, 0.952 to 0.999). Veracity was also confirmed in the validation cohort (40 GC patients) with AUC 0.950 (0.889 to 0.999). High predicted score was correlated with better DFS in the patients with stage I-III and lower OS with stage I-IV. CONCLUSION: This study identify 16 LncRNAs signatures able to classify MSI status. The correlation between lncRNAs and MSI status indicates the potential roles of lncRNAs interacting in immunotherapy for GC patients. The pathway of these lncRNAs which might be a target in PD-1/PD-L1 immunotherapy are needed to be further study.