Biochemical and Transcriptome Analyses Reveal a Stronger Capacity for Photosynthate Accumulation in Low-Tillering Rice Varieties.

Moderate control of rice tillering and the development of rice varieties with large panicles are important topics for future high-yield rice breeding. Herein, we found that low-tillering rice varieties stopped tillering earlier and had a larger leaf area of the sixth leaf. Notably, at 28 days after sowing, the rice seedlings of the low-tillering group had an average single-culm above-ground biomass of 0.84 g, significantly higher than that of the multi-tillering group by 56.26%, and their NSC (non-structural carbohydrate) and starch contents in sheaths were increased by 43.34% and 97.75%, respectively. These results indicated that the low-tillering group of rice varieties had a stronger ability to store photosynthetic products in the form of starch in their sheaths, which was thus more beneficial for their large panicle development. The results of carbon and nitrogen metabolism analyses showed that the low-tillering group had a relatively strong carbon metabolism activity, which was more favorable for the accumulation of photosynthesis products and the following development of large panicles, while the multi-tillering group showed relatively strong nitrogen metabolism activity, which was more beneficial for the development and formation of new organs, such as tillers. Accordingly, in the low-tillering rice varieties, the up-regulated genes were enriched in the pathways mainly related to the synthesis of carbohydrates, while the down-regulated genes were mainly enriched in the nitrogen metabolism pathways. This study provides new insights into the mechanism of rice tillering regulation and promotes the development of new varieties with ideal plant types.

A novel laparoscopic pancreaticoduodenal training model: optimization of the learning curve and simplification of postoperative complications.

PURPOSE: Laparoscopic pancreaticoduodenectomy requires a long learning curve. A preoperative training system was established to optimize the surgeons' learning curve and reduce the incidence rate of complications at the beginning of the curve. METHODS: The laparoscopic pancreaticojejunostomy model, and choledochojejunostomy and gastrojejunostomy training systems were developed, and corresponding evaluation systems were also defined. Surgeons B and C performed laparoscopic pancreaticoduodenectomy after completing training session. Surgical outcomes, postoperative complications and their learning curves were analyzed. RESULTS: Patients operated by surgeons B and C experienced shorter operative durations following training session than those in nontrained group (called A) ( P <0.001). B and C began entering the inflection point at the 26th and 20th case in learning curve, respectively. The incidence of postoperative pancreatic fistula in group B was 3.3%, significantly lower than 13.1% in group A ( P =0.047). Patients in group B showed significantly lower incidence of biliary-enteric anastomosis leakage (0% vs. 8.2%, P =0.029) and Clavien-Dindo classification greater than or equal to 3 (3.3% vs. 14.8%, P =0.027) compared with those in group A. The incidence of surgical site infection in groups B (3.3%, P =0.004) and C (4.9%, P =0.012) was significantly lower than that in group A (19.7%). Moreover, the length of postoperative hospital stay was significantly shorter in groups B (12.5±5.9 days, P =0.002) and C (13.7±6.5 days, P =0.002) compared with group A (16.7±8.5 days). CONCLUSIONS: The laparoscopic pancreaticojejunostomy training model and evaluation system can shorten the operative duration, lower the risk of postoperative complications, and shorten the length of hospital stay.

Transcriptome Analysis Reveals the Dynamic and Rapid Transcriptional Reprogramming Involved in Heat Stress and Identification of Heat Response Genes in Rice.

High temperature is one of the most important environmental factors influencing rice growth, development, and yield. Therefore, it is important to understand how rice plants cope with high temperatures. Herein, the heat tolerances of T2 (Jinxibai) and T21 (Taizhongxianxuan2hao) were evaluated at 45 °C, and T21 was found to be sensitive to heat stress at the seedling stage. Analysis of the H2O2 and proline content revealed that the accumulation rate of H2O2 was higher in T21, whereas the accumulation rate of proline was higher in T2 after heat treatment. Meanwhile, transcriptome analysis revealed that several pathways participated in the heat response, including "protein processing in endoplasmic reticulum", "plant hormone signal transduction", and "carbon metabolism". Additionally, our study also revealed that different pathways participate in heat stress responses upon prolonged stress. The pathway of "protein processing in endoplasmic reticulum" plays an important role in stress responses. We found that most genes involved in this pathway were upregulated and peaked at 0.5 or 1 h after heat treatment. Moreover, sixty transcription factors, including the members of the AP2/ERF, NAC, HSF, WRKY, and C2H2 families, were found to participate in the heat stress response. Many of them have also been reported to be involved in biotic or abiotic stresses. In addition, through PPI (protein-protein interactions) analysis, 22 genes were identified as key genes in the response to heat stress. This study improves our understanding of thermotolerance mechanisms in rice, and also lays a foundation for breeding thermotolerant cultivars via molecular breeding.

Time-Series Transcriptomic Analysis of Contrasting Rice Materials under Heat Stress Reveals a Faster Response in the Tolerant Cultivar.

Short-term heat stress can affect the growth of rice (Oryza sativa L.) seedlings, subsequently decreasing yields. Determining the dynamic response of rice seedlings to short-term heat stress is highly important for accelerating research on rice heat tolerance. Here, we observed the seedling characteristics of two contrasting cultivars (T11: heat-tolerant and T15: heat-sensitive) after different durations of 42 °C heat stress. The dynamic transcriptomic changes of the two cultivars were monitored after 0 min, 10 min, 30 min, 1 h, 4 h, and 10 h of stress. The results indicate that several pathways were rapidly responding to heat stress, such as protein processing in the endoplasmic reticulum, glycerophospholipid metabolism, and plant hormone signal transduction. Functional annotation and cluster analysis of differentially expressed genes at different stress times indicate that the tolerant cultivar responded more rapidly and intensively to heat stress compared to the sensitive cultivar. The MAPK signaling pathway was found to be the specific early-response pathway of the tolerant cultivar. Moreover, by combining data from a GWAS and RNA-seq analysis, we identified 27 candidate genes. The reliability of the transcriptome data was verified using RT-qPCR on 10 candidate genes and 20 genes with different expression patterns. This study provides valuable information for short-term thermotolerance response mechanisms active at the rice seedling stage and lays a foundation for breeding thermotolerant varieties via molecular breeding.

Clinical and genetic characteristics in pancreatic cancer from Chinese patients revealed by whole exome sequencing.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies worldwide, mostly as a result of the absence of early detection and specific treatment solutions. Consequently, identifying mutational profiles and molecular biomarkers is essential for increasing the viability of precision therapy for pancreatic cancer. Methods: We collected blood and tumor tissue samples from 47 Chinese pancreatic cancer patients and used whole-exome sequencing (WES) to evaluate the genetic landscape. Results: Our results showed the most frequently somatic alteration genes were KRAS (74.5%), TP53(51.1%), SMAD4 (17%), ARID1A (12.8%), CDKN2A (12.8%), TENM4 (10.6%), TTN (8.5%), RNF43(8.5%), FLG (8.5%) and GAS6 (6.4%) in Chinese PDAC patients. We also found that three deleterious germline mutations (ATM c.4852C>T/p. R1618*, WRN c.1105C>T/p. R369*, PALB2 c.2760dupA/p. Q921Tfs*7) and two novel fusions (BRCA1-RPRML, MIR943 (intergenic)-FGFR3). When compared to the Cancer Genome Atlas (TCGA) database, there is a greater mutation frequency of TENM4 (10.6% vs. 1.6%, p = 0.01), GAS6(6.4% vs. 0.5%, p = 0.035), MMP17(6.4% vs. 0.5%, p = 0.035), ITM2B (6.4% vs. 0.5%, p = 0.035) and USP7 (6.4% vs. 0.5%, p= 0.035) as well as a reduced mutation frequency of SMAD4 (17.0% vs. 31.5%, p = 0.075) and CDKN2A (12.8% vs. 47.3%, p < 0.001) were observed in the Chinese cohort. Among the 41 individuals examined for programmed cell death ligand 1(PD-L1) expression, 15 (36.6%) had positive PD-L1 expression. The median tumor mutational burden (TMB) was found to be 12muts (range, 0124). The TMB index was higher in patients with mutant-type KRAS MUT/TP53 MUT (p < 0.001), CDKN2A (p = 0.547), or SMAD4 (p = 0.064) compared to patients with wild-type KRAS/TP53, CDKN2A, or SMAD4. Conclusions: We exhibited real-world genetic traits and new alterations in Chinese individuals with cancer of the pancreas, which might have interesting implications for future individualized therapy and medication development.

Molecular Evolution of Histone Methylation Modification Families in the Plant Kingdom and Their Genome-Wide Analysis in Barley.

In this study, based on the OneKP database and through comparative genetic analysis, we found that HMT and HDM may originate from Chromista and are highly conserved in green plants, and that during the evolution from algae to land plants, histone methylation modifications gradually became complex and diverse, which is more conducive to the adaptation of plants to complex and variable environments. We also characterized the number of members, genetic similarity, and phylogeny of HMT and HDM families in barley using the barley pangenome and the Tibetan Lasa Goumang genome. The results showed that HMT and HDM were highly conserved in the domestication of barley, but there were some differences in the Lasa Goumang SDG subfamily. Expression analysis showed that HvHMTs and HvHDMs were highly expressed in specific tissues and had complex expression patterns under multiple stress treatments. In summary, the amplification and variation of HMT and HDM facilitate plant adaptation to complex terrestrial environments, while they are highly conserved in barley and play an important role in barley growth and development with abiotic stresses. In brief, our findings provide a novel perspective on the origin and evolutionary history of plant HvHMTs and HvHDMs, and lay a foundation for further investigation of their functions in barley.

Cancer stem cell-like cells-derived exosomal lncRNA CDKN2B-AS1 promotes biological characteristics in thyroid cancer via miR-122-5p/P4HA1 axis.

Introduction: Here, the discussion focused on the function and possible mechanism of cancer stem cell-like cells (CSCs)-derived exosomal CDKN2B-AS1 in thyroid cancer. Methods: Specifically, the bioinformatics analysis, dual-luciferase reporter assay and RT-qPCR were conducted to obtain the expression and regulation of CDKN2B-AS1, and the downstream miR-122-5p/P4HA1 axis. Exosomes were identified by transmission electron microscopy. The uptake of exosome by recipient cells was observed by PKH67 labeling. Functional experiments and western blot were adopted to detect the effects of exosomal CDKN2B-AS1/miR-122-5p/P4HA1 axis on thyroid cancer cells. Tumor xenograft and in vivo metastasis model combined with RT-qPCR, western blot and hematoxylin-eosin staining verified the role of CDKN2B-AS1. Results: Exosomal CDKN2B-AS1 up-regulated P4HA1 expression through miR-122-5p. CDKN2B-AS1 and P4HA1 expressions were up-regulated, and miR-122-5p expression was down-regulated in thyroid cancer. Silent CDKN2B-AS1 reduced cell viability and stemness. CDKN2B-AS1 was found to be abundant in CSCs and CSCs-derived exosomes. Exosomal CDKN2B-AS1 silencing could transfer to thyroid cancer cells to elevate E-cadherin level, and diminish P4HA1, N-cadherin and Vimentin levels, thus impeding cell migration and invasion. MiR-122-5p inhibitor reversed the function of exosomal CDKN2B-AS1, while P4HA1 silencing attenuated the effect of miR-122-5p inhibitor. Exosomal CDKN2B-AS1 affected the growth and metastasis of thyroid cancer through the miR-122-5p/P4HA1 axis. Conclusion: CSCs-derived exosomal CDKN2B-AS1 acts as an oncogene in thyroid cancer through miR-122-5p/P4HA1 axis.

Comparison of Efficacy and Safety Between Laparoscopic and Open Radical Resection for Hilar Cholangiocarcinoma-A Propensity Score-Matching Analysis.

Background: Radical resection remains the most effective treatment for hilar cholangiocarcinoma (HCCA). However, due to the complex anatomy of the hilar region, the tumor is prone to invade portal vein and hepatic arteries, making the surgical treatment of HCCA particularly difficult. Successful laparoscopic radical resection of HCCA(IIIA, IIIB) requires excellent surgical skills and rich experience. Furthermore, the safety and effectiveness of this operation are still controversial. Aim: To retrospectively analyze and compare the efficacy and safety of laparoscopic and open surgery for patients with HCCA. Methods: Clinical imaging and postoperative pathological data of 89 patients diagnosed with HCCA (IIIA, IIIB) and undergoing radical resection in our center from January 2018 to March 2022 were retrospectively analyzed. Among them, 6 patients (4 were lost to follow-up and 2 were pathologically confirmed to have other diseases after surgery) were ruled out, and clinical data was collected from the remaining 83 patients for statistical analysis. These patients were divided into an open surgery group (n=62) and a laparoscopic surgery group (n=21) according to the surgical methods used, and after 1:2 propensity score matching (PSM), 32 and 16 patients respectively in the open surgery group and laparoscopic surgery group were remained. The demographic data, Bismuth type, perioperative data, intraoperative data, postoperative complications, pathological findings, and long-term survivals were compared between these two groups. Results: After 1:2 PSM, 32 patients in the open surgery group and 16 patients in the laparoscopic surgery group were included for further analysis. Baseline characteristics and pathological outcomes were comparable between the two groups. Statistically significant differences between the two groups were observed in intraoperative blood loss and operative time, as it were 400-800 mL vs 200-400 mL (P=0.012) and (407.97 ± 76.06) min vs (489.69 ± 79.17) min (P=0.001) in the open surgery group and laparoscopic surgery group, respectively. The R0 resection rate of the open group was 28 cases (87.5%), and the R0 resection rate of the laparoscopic group was 15 cases (93.75%). The two groups showed no significant difference in terms of surgical approach, intraoperative blood transfusion, incidence of postoperative complications, and short- and long-term efficacy (P>0.05). Conclusions: Laparoscopic radical resection of HCCA has comparable perioperative safety compared to open surgery group, as it has less bleeding and shorter operation time. Although it is a promising procedure with the improvement of surgical skills and further accumulation of experience, further investigations are warranted before its wider application.

Efficacy and safety of laparoscopic radical resection following neoadjuvant therapy for pancreatic ductal adenocarcinoma: A retrospective study.

BACKGROUND: Multiple studies have demonstrated that neoadjuvant chemotherapy (NACT) can prolong the overall survival of pancreatic ductal adenocarcinoma (PDAC) patients. However, most studies have focused on open surgery following NACT. AIM: To investigate the efficacy and safety of laparoscopic radical resection following NACT for PDAC. METHODS: We retrospectively analyzed the clinical data of 15 patients with pathologically confirmed PDAC who received NACT followed by laparoscopic radical surgery in our hospital from December 2019 to April 2022. All patients underwent abdominal contrast-enhanced computed tomography (CT) and positron emission tomography-CT before surgery to accurately assess tumor stage and exclude distant metastasis. RESULTS: All 15 patients with pancreatic cancer were successfully converted to surgical resection after NACT, including 8 patients with pancreatic head cancer and 7 patients with pancreatic body and tail cancer. Among them, 13 patients received the nab-paclitaxel plus gemcitabine regimen (gemcitabine 1000 mg/m2 plus nab-paclitaxel 125 mg/m2 on days 1, 8, and 15 every 4 wk) and 2 patients received the modified FOLFIRINOX regimen (intravenous oxaliplatin 68 mg/m2, irinotecan 135 mg/m2, and leucovorin 400 mg/m2 on day 1 and fluorouracil 400 mg/m2 on day 1, followed by 46-h continuous infusion of fluorouracil 2400 mg/m2). After each treatment cycle, abdominal CT, tumor markers, and circulating tumor cell counts were reviewed to evaluate the treatment efficacy. All 15 patients achieved partial remission. The surgical procedures included laparoscopic pancreaticoduodenectomy (LPD, n = 8) and laparoscopic radical antegrade modular pancreatosplenectomy (L-RAMPS, n = 7). None of them were converted to a laparotomy. One patient with pancreatic head carcinoma was found to have portal vein involvement during the operation, and LPD combined with vascular resection and reconstruction was performed. The amount of blood loss and operation times of L-RAMPS vs LPD were 435.71 ± 32.37 mL vs 343.75 ± 145.01 mL and 272.52 ± 49.14 min vs 444.38 ± 68.63 min, respectively. The number of dissected lymph nodes was 16.87 ± 4.10, and 3 patients had positive lymph nodes. One patient developed grade B postoperative pancreatic fistula (POPF) after L-RAMPS, and one patient experienced jaundice after LPD. None of the patients died after surgery. As of April 2022, progressive disease was noted in 4 patients, 2 patients had liver metastasis, and one had both liver metastasis and lymph node metastasis and died during the follow-up period. CONCLUSION: Laparoscopic radical resection of PDAC after NACT is safe and effective if it is performed by a surgeon with rich experience in LPD and in a large center of pancreatic surgery.

Preliminary experience on laparoscopic pancreaticoduodenal combined with major venous resection and reconstruction anastomosis.

Objective: This study aims to summarize our experience in laparoscopic pancreatoduodenectomy (LPD) combined with major venous resection and reconstruction, as well as to evaluate its safety and discuss the surgical approach. Methods: We retrospectively analyzed 14 cases of patients diagnosed with pancreatic tumors invaded the superior mesenteric vein or portal vein who had undergone LPD combined with major venous resection and reconstruction in our center from May 2016 to May 2020. Clinical data of these 14 patients were collected and analyzed, including general information (age, gender, pathological diagnosis, body mass index, etc.), intraoperative data (operation time, intraoperative blood loss, transit rate, blood transfusion, tumor diameter, R0 resection rate, cleaning lymph node number, removal vessel length, venous reconstruction time), and postoperative results (gastrointestinal function recovery, postoperative hospital time, complications, and fatality rate). Patients were followed up after surgery, and data were collected for statistical analysis. Results: A total of 14 patients (9 males and 5 females) received LPD combined with major venous resection and reconstruction by arterial approach. The mean age was 52.5 (43-74) years old. Three of these 14 patients had routine wedge resection, 9 had opposite-to-end anastomosis after venous resection, 2 had artificial venous replacement, and the average length of removal vessel was 3.1 (2-4.5) cm. The operation time was 395 (310-570) min; the venous blocking time was 29.7 (26-50) min; the hospitalization stay was 13.6 (9-39) days. There was no grade B or C postoperative pancreatic fistula (POPF) that occurred, only one patient had biochemical fistula. One patient had upper gastrointestinal bleeding after subcutaneous injection of low molecular weight (LMW) heparin, and the condition was alleviated after conservative treatment, and one had pulmonary infection. The 12-month disease-free survival rate was 85.7%, and the 12-month overall survival rate was 92.8%. No patients had 30-day re-admission or death. Conclusion: On the basis of the surgeon's proficiency in open pancreatoduodenectomy combined with venous resection and reconstruction and standard LPD, the arterial approach for LPD combined with major venous resection and reconstruction is safe and feasible.

Association of a Modified Blumgart Anastomosis With the Incidence of Pancreatic Fistula and Operation Time After Laparoscopic Pancreatoduodenectomy: A Cohort Study.

Objective: To explore the association between a modified Blumgart anastomosis technique and the operative time and surgical complications. Methods: This is a retrospective cohort study that analyzed the data of patients who underwent laparoscopic pancreaticoduodenectomy from January 2015 to March 2021. The primary outcome was to explore the association between the modified Blumgart anastomosis technique and operative time. Results: A total of 282 patients were enrolled. There were 177 cases of pancreatic duct-to-mucosa anastomosis in the traditional surgery group, and 105 cases of the modified three-step Blumgart anastomosis in the modified group. There were no statistically significant differences in the general and intraoperative characteristics found between the two groups (P > 0.05). The surgical method was an independent predictor of operative time. Overall complications postsurgery were less common in the modified group than in the traditional group. The incidence of postoperative pancreatic fistula was higher in the traditional group than in the modified group (45 cases (25.4%) and 11 cases (10.5%), respectively). Fourteen cases (7.9%) in the traditional group and four case (3.8%) in the modified group had postoperative pancreatic fistula of grades B + C. The two groups had statistically significant differences (P < 0.05). The results of the linear regression showed that the type of surgical method was associated with operation time (95% CI, -73.074 to -23.941, ß: -0.438, P < 0.001). Conclusion: This modified three-step Blumgart pancreaticojejunostomy was associated with the operation time.

The Mutational, Epigenetic, and Transcriptional Effects Between Mixed High-Energy Particle Field (CR) and 7Li-Ion Beams (LR) Radiation in Wheat M1 Seedlings.

Ionizing radiation (IR) is an effective approach for mutation breeding. Understanding the mutagenesis and transcriptional profiles induced by different mutagens is of great significance for improving mutation breeding efficiency. Here, using RNA sequencing and methylation-sensitive amplification polymorphism (MSAP) approaches, we compared the genetic variations, epigenetics, and transcriptional responses induced by the mixed high-energy particle field (CR) and 7Li-ion beam (LR) radiation in M1 seedlings of two wheat genotypes (Yangmai 18 and Yangmai 20). The results showed that, in both wheat genotypes, CR displayed significantly a higher mutation efficiency (1.79 × 10-6/bp) than that by LR (1.56 × 10-6/bp). The induced mutations were not evenly distributed across chromosomes and varied across wheat genotypes. In Y18 M1, the highest number of mutations were detected on Chr. 6B and Chr. 6D, whilst in Y20 M1, Chr. 7A and Chr. 3A had the highest mutations. The transcript results showed that total of 4,755 CR-regulated and 1,054 LR-regulated differentially expressed genes (DEGs) were identified in the both genotypes. Gene function enrichment analysis of DEGs showed that these DEGs overlapped or diverged in the cascades of molecular networks involved in "phenylpropanoid biosynthesis" and "starch and sucrose metabolism" pathways. Moreover, IR type specific responses were observed between CR an LR irradiation, including specific TFs and response pathways. MSAP analysis showed that DNA methylation level increased in LR treatment, while decreased at CR. The proportion of hypermethylation was higher than that of hypomethylation at LR, whereas a reverse pattern was observed at CR, indicating that DNA methylation plays critical roles in response to IR irradiation. All these results support that the response to different IRs in wheat includes both common and unique pathways, which can be served as a useful resource to better understand the mechanisms of responses to different IRs in other plants.

Cancer stem cell-like cells-derived exosomal CDKN2B-AS1 stabilizes CDKN2B to promote the growth and metastasis of thyroid cancer via TGF-ß1/Smad2/3 signaling.

As CDKN2B-AS1 is demonstrated to exert promotive effects on thyroid cancer (TC), this research aims to investigate the role of cancer stem cell-like cells (CSCs)-derived exosomal CDKN2B-AS1 in TC and the underlying regulatory mechanism. Specifically, CDKN2B expression and the correlation of CDKN2B with CDKN2B-AS1 in TC were determined via bioinformatics analysis and further verified by qRT-PCR. After transfection or co-culture with CSCs-derived exosomes, viability, migration, and invasion of TPC-1 and SW579 cells were evaluated by CCK-8, wound healing, and transwell assays, respectively. The uptake of exosomes by TC cells was detected by PKH67 labeling. In vivo tumor formation and metastasis models were established. Tumor volume and weight were calculated. Metastasis loci in lung tissues were observed by hematoxylin-eosin staining. The expression levels of CDKN2B-AS1, CDKN2B, and epithelial-mesenchymal transition- and TGF-ß1/Smad2/3 signaling-related factors were detected by qRT-PCR or Western blot. Concretely, CDKN2B and CDKN2B-AS1 were highly expressed in TC, and there was a positive correlation between the two. In addition, CDKN2B-AS1 promoted the translation and stability of CDKN2B. Furthermore, CDKN2B-AS1 was highly expressed in CSCs and CSCs-derived exosomes which could be absorbed by TC cells. CDKN2B silencing inhibited viability, migration, invasion, protein levels of CDKN2B, N-cadherin and Vimentin, and TGF-ß1/Smad2/3 signaling, while promoting E-cadherin expression in TC cells. CSCs-derived exosomal CDKN2B-AS1 did oppositely and reversed the effects of CDKN2B silencing on TC cells. CDKN2B silencing impeded tumor growth and metastasis in TC mice, while TGF-ß1 performed inversely and impaired the effects of CDKN2B silencing. Collectively, CSCs-derived exosomal CDKN2B-AS1 stabilizes CDKN2B to promote growth and metastasis of TC via TGF-ß1/Smad2/3 signaling.

Camrelizumab Combined With Gemcitabine and Albumin-Bound Paclitaxel for Neoadjuvant Therapy in the Treatment of Progressive Gallbladder Cancer: A Case Report.

Background: The roles of immune checkpoint inhibitors in the treatment of gallbladder cancer are still unclear and challenged by controversial findings. Recent research has shown that immune checkpoint inhibitors in combination with chemotherapy may alleviate disease progression. Case Summary: A 45-year-old female patient with gallbladder cancer accompanied by multiple abdominal lymph node metastasis was treated with camrelizumab combined with paclitaxel for injection (albumin-bound) and gemcitabine (AG) to downstage the tumor before a radical surgery could be performed. The postoperative quality of life was superior to the preoperative level. Conclusion: Camrelizumab + AG offers a new therapeutic option for gallbladder cancer with multiple abdominal lymph node metastasis, which, however, warrants further validation in clinical trials.

Recent Advances in Bioinspired Hydrogels with Environment-Responsive Characteristics for Biomedical Applications.

The development of hydrogel-integrated soft materials via the incorporation of therapeutic medicines into biocompatible hydrogels, serving as host, will significantly contribute to advances in medical diagnosis and treatment. Furthermore, intelligent hydrogels having the ability to respond to local environmental conditions offer a promising approach for the development of novel solutions in the biomedical field. Bioinspired intelligent hydrogels are now becoming a potentially powerful biomaterial class for tissue engineering, drug delivery, and medical device. Recent advances include bioinspired intelligent hydrogels that possess unique mechanical and optical properties as a result of their nature-inspired complex-structured design. This review highlights the latest advances in intelligent bionic hydrogels, as well as strategies targeting smart response of their characteristics across multiple dimensions (such as temperature, light, pH, among others). Finally, the potential development and prospective application of mimicking the natural intelligence of multifunctional medical hydrogels are also discussed.

ipa1 improves rice drought tolerance at seedling stage mainly through activating abscisic acid pathway.

KEY MESSAGE: ipa1 enhances rice drought tolerance mainly through activating the ABA pathway. It endows rice seedlings with a more developed root system, smaller leaf stomata aperture, and enhanced carbon metabolism. Drought is a major abiotic stress to crop production. IPA1 (IDEAL PLANT ARCHITECTURE 1)/OsSPL14 encodes a transcription factor and has been reported to function in both rice ideal plant architecture and biotic resistance. Here, with a pair of IPA1 and ipa1-NILs (Near Iso-genic Lines), we found that ipa1 could significantly improve rice drought tolerance at seedling stage. The ipa1 plants had a better-developed root system and smaller leaf stomatal aperture. Analysis of carbon-nitrogen metabolism-associated enzyme activity, gene expression, and metabolic profile indicated that ipa1 could tip the carbon-nitrogen metabolism balance towards an increased carbon metabolism pattern. In both the control and PEG-treated conditions, ABA content in the ipa1 seedlings was significantly higher than that in the IPA1 seedlings. Expression of the ABA biosynthesis genes was detected to be up-regulated, whereas the expression of ABA catabolism genes was down-regulated in the ipa1 seedlings. In addition, based on yeast one-hybrid assay and dual-luciferase assay, IPA1 was found to directly activate the promoter activity of OsHOX12, a transcription factor promoting ABA biosynthesis, and OsNAC52, a positive regulator of the ABA pathway. The expression of OsHOX12 and OsNAC52 was significantly up-regulated in the ipa1 plants. Combined with the previous studies, our results suggested that ipa1 could improve rice seedling drought tolerance mainly through activating the ABA pathway and that regulation of the ipa1-mediated ABA pathway will be an important strategy for improving drought resistance of rice.

Sequential therapy with combined trans-papillary endoscopic naso-pancreatic and endoscopic retrograde pancreatic drainage for pancreatic pseudocysts.

BACKGROUND: Endoscopic retrograde pancreatic drainage (ERPD) and stent implantation has become the major treatment method for pancreatic pseudocysts. However, it is associated with a high recurrence rate and infection. AIM: To manage pancreatic pseudocysts by sequential therapy with endoscopic naso-pancreatic drainage (ENPD) combined with ERPD and evaluate the treatment outcome. METHODS: One hundred and sixty-two cases of pancreatic pseudocyst confirmed by endoscopic examination at our hospital between January 2014 and January 2020 were retrospectively analyzed. There were 152 cases of intubation via the duodenal papilla, of which 92 involved pancreatic duct stent implantation and 60 involved sequential therapy with combined ENPD and ERPD (two-step procedure). The success rate of the procedure, incidence of complications (infection, bleeding, etc.), recurrence, and length and cost of hospitalization were compared between the two groups. RESULTS: The incidence of infection was significantly higher in the ERPD group (12 cases) than in the two-step procedure group (2 cases). Twelve patients developed infection in the ERPD group, and anti-infection therapy was effective in five cases but not in the remaining seven cases. Infection presented as fever and chills in the two-step procedure group. The reoperation rate was significantly higher in the ERPD group with seven cases compared with zero cases in the two-step procedure group (P < 0.05). Similarly, the recurrence rate was significantly higher in the ERPD group (19 cases) than in the two-step procedure group (0 cases). CONCLUSION: Sequential therapy with combined ENPD and ERPD is safe and effective in patients with pancreatic pseudocysts.

High-Efficiency, Dual-Band Beam Splitter Based on an All-Dielectric Quasi-Continuous Metasurface.

Metasurface-based beam splitters attracted huge interest for their superior properties compared with conventional ones made of bulk materials. The previously reported designs adopted discrete metasurfaces with the limitation of a discontinuous phase profile. In this paper, we propose a dual-band beam splitter, based on an anisotropic quasi-continuous metasurface, by exploring the optical responses under x-polarized (with an electric field parallel to the direction of the phase gradient) and y-polarized incidences. The adopted metasurface consists of two identical trapezoidal silicon antenna arrays with opposite spatial variations that lead to opposite phase gradients. The operational window of the proposed beam splitter falls in the infrared and visible region, respectively, for x- and y-polarized light, resulting from the different mechanisms. When x-polarized light is incident, the conversion efficiency and total transmission of the beam splitter remains higher than 90% and 0.74 within the wavelength range from 969 nm to 1054 nm, respectively. In this condition, each array can act as a beam splitter of unequal power. For y-polarized incidence, the maximum conversion efficiency and transmission reach approximately 100% and 0.85, while the values remain higher than 90% and 0.65 in the wavelength range from 687 nm to 710 nm, respectively. In this case, each array can be viewed as an effective beam deflector. We anticipate that it can play a key role in future integrated optical devices.

IPA1 Negatively Regulates Early Rice Seedling Development by Interfering with Starch Metabolism via the GA and WRKY Pathways.

Ideal Plant Architecture 1 (IPA1) encodes SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 14 (SPL14) with a pleiotropic effect on regulating rice development and biotic stress responses. To investigate the role of IPA1 in early seedling development, we developed a pair of IPA1/ipal-NILs and found that seed germination and early seedling growth were retarded in the ipa1-NIL. Analysis of the soluble sugar content, activity of amylase, and expression of the α-amylase genes revealed that the starch metabolism was weakened in the ipa1-NIL germinating seeds. Additionally, the content of bioactive gibberellin (GA) was significantly lower than that in the IPA1-NIL seeds at 48 h of imbibition. Meanwhile, the expression of GA synthesis-related gene OsGA20ox1 was downregulated, whereas the expression of GA inactivation-related genes was upregulated in ipa1-NIL seeds. In addition, the expression of OsWRKY51 and OsWRKY71 was significantly upregulated in ipa1-NIL seeds. Using transient dual-luciferase and yeast one-hybrid assays, IPA1 was found to directly activate the expression of OsWRKY51 and OsWRKY71, which would interfere with the binding affinity of GA-induced transcription factor OsGAMYB to inhibit the expression of α-amylase genes. In summary, our results suggest that IPA1 negatively regulates seed germination and early seedling growth by interfering with starch metabolism via the GA and WRKY pathways.