Synergistic interaction between ABA and IAA due to moderate soil drying promotes grain filling of inferior spikelets in rice.

Poor grain filling of inferior spikelets is becoming a severe problem in some super rice varieties with large panicles. Moderate soil drying (MD) after pollination has been proven to be a practical strategy to promote grain filling. However, the molecular mechanisms underlying this phenomenon remain largely unexplored. Here, transcriptomic analysis of the most active grain filling stage revealed that both starch metabolism and phytohormone signaling were significantly promoted by MD treatment, accompanied by increased enzyme activities of starch synthesis and elevated abscisic acid (ABA) and indole-3-acetic acid (IAA) content in the inferior spikelet. Moreover, the IAA biosynthesis genes OsYUC11 and OsTAR2 were upregulated, while OsIAA29 and OsIAA24, which encode two repressors of auxin signaling, were downregulated by MD, implying a regulation of both IAA biosynthesis and auxin signal transduction in the inferior spikelet by MD. A notable improvement in grain filling of the inferior spikelet was found in the aba8ox2 mutant, which is mutated in an ABA catabolism gene. In contrast, overexpression of OsABA8ox2 significantly reduced grain filling. Interestingly, not only the IAA content, but also the expression of IAA biosynthesis and auxin-responsive genes displayed a similar trend to that in the inferior spikelet under MD. In addition, several OsTPP genes were downregulated in the inferior spikelets of both MD/ABA-treated wild-type plants and the aba8ox2 mutant, resulting in lower trehalose content and higher levels of -6-phosphate (T6P), thereby increasing the expression of OsTAR2, a target of T6P. Taken together, our results suggest that the synergistic interaction of ABA-mediated accumulation of IAA promotes grain filling of inferior spikelets under MD.

The chromatin accessibility landscape of pistils and anthers in rice.

Transcription activation is tightly associated with the openness of chromatin and allows direct contact between transcriptional regulators and their targeted DNA for gene expression. However, there are limited studies on the annotation of open chromatin regions (OCRs) in rice (Oryza sativa), especially those in reproductive organs. Here, we characterized OCRs in rice pistils and anthers with an assay for transposase-accessible chromatin using sequencing. Despite a large overlap, we found more OCRs in pistils than in anthers. These OCRs were enriched in gene transcription start sites (TSSs) and showed tight associations with gene expression. Transcription factor (TF) binding motifs were enriched at these OCRs as validated by TF chromatin immunoprecipitation followed by sequencing. Pistil-specific OCRs provided potential regulatory networks by binding directly to the targets, indicating that pistil-specific OCRs may be indicators of cis-regulatory elements in regulating pistil development, which are absent in anthers. We also found that open chromatin of pistils and anthers responded differently to low temperature (LT). These data offer a comprehensive overview of OCRs regulating reproductive organ development and LT responses in rice.

Intratumoral and Peritumoral Radiomics Based on Preoperative MRI for Evaluation of Programmed Cell Death Ligand-1 Expression in Breast Cancer.

BACKGROUND: Programmed cell death ligand-1 (PD-L1) is a promising target for immune checkpoint blockade therapy in breast cancer. However, the preoperative evaluation of PD-L1 expression in breast cancer is rarely explored. PURPOSE: To determine the ability of radiomics signatures based on preoperative dynamic contrast-enhanced (DCE) MRI to evaluate PD-L1 expression in breast cancer. STUDY TYPE: Retrospective. POPULATION: 196 primary breast cancer patients with preoperative MRI and postoperative pathological evaluation of PD-L1 expression, divided into training (n = 137, 28 PD-L1-positive) and test cohorts (n = 59, 12 PD-L1-positive). FIELD STRENGTH/SEQUENCE: 3.0T; volume imaging for breast assessment DCE sequence. ASSESSMENT: Radiomics features were extracted from the first phase of DCE-MRI by using the minimum redundancy maximum relevance method and least absolute shrinkage and selection operator algorithm. Three radiomics signatures were constructed based on the intratumoral, peritumoral, and combined intra- and peritumoral regions. The performance of the signatures was assessed using area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity, and accuracy. STATISTICAL TESTS: Univariable and multivariable logistic regression analysis, t-tests, chi-square tests, Fisher exact test or Yates correction, ROC analysis, and one-way analysis of variance. P < 0.05 was considered significant. RESULTS: In the test cohort, the combined radiomics signature (AUC, 0.853) exhibited superior performance compared to the intratumoral (AUC, 0.816; P = 0.528) and peritumoral radiomics signatures (AUC, 0.846; P = 0.905) in PD-L1 status evaluation, although the differences did not reach statistical significance. DATA CONCLUSION: Intratumoral and peritumoral radiomics signatures based on preoperative breast MRI showed some potential accuracy for the non-invasive evaluation of PD-L1 status in breast cancer. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

Overexpression of LaGRAS enhances phosphorus acquisition via increased root growth of phosphorus-deficient white lupin.

The GRAS transcription factors play an indispensable role in plant growth and responses to environmental stresses. The GRAS gene family has extensively been explored in various plant species; however, the comprehensive investigation of GRAS genes in white lupin remains insufficient. In this study, bioinformatics analysis of white lupin genome revealed 51 LaGRAS genes distributed into 10 distinct phylogenetic clades. Gene structure analyses revealed that LaGRAS proteins were considerably conserved among the same subfamilies. Notably, 25 segmental duplications and a single tandem duplication showed that segmental duplication was the major driving force for the expansion of GRAS genes in white lupin. Moreover, LaGRAS genes exhibited preferential expression in young cluster root and mature cluster roots and may play key roles in nutrient acquisition, particularly phosphorus (P). To validate this, RT-qPCR analysis of white lupin plants grown under +P (normal P) and -P (P deficiency) conditions elucidated significant differences in the transcript level of GRAS genes. Among them, LaGRAS38 and LaGRAS39 were identified as potential candidates with induced expression in MCR under -P. Additionally, white lupin transgenic hairy root overexpressing OE-LaGRAS38 and OE-LaGRAS39 showed increased root growth, and P concentration in root and leaf compared to those with empty vector control, suggesting their role in P acquisition. We believe this comprehensive analysis of GRAS members in white lupin is a first step in exploring their role in the regulation of root growth, tissue development, and ultimately improving P use efficiency in legume crops under natural environments.

Anlotinib Combined with Toripalimab as Second-Line Therapy for Advanced, Relapsed Gastric or Gastroesophageal Junction Carcinoma.

Our study aimed to explore the efficacy and safety of anlotinib-toripalimab combination therapy as a second-line treatment for advanced relapsed gastric or gastroesophageal junction carcinoma (GC/GEJC). In this single arm, single-center extension clinical trial, patients with advanced relapsed GC/GEJC received toripalimab (240 mg, intravenously over 60 minutes, once every 2 weeks) plus anlotinib (12 mg/day, orally, 2 weeks on and 1 week off, every 3 weeks) as second-line therapy. There were 29 patients who achieved partial response, and the ORR was 32.3% (95% CI, 26.6%-38.5%). Grade 3 treatment-related adverse events (TRAEs) were recorded in 7 participants (11.3%), all of which were manageable. The PFS and OS were 4.0 and 11.1 months, respectively. Patients with programmed death-ligand 1 (PD-L1) positive expression showed numerically longer OS than the negative ones although the difference was not significantly. The tumor mutational burden-high (TMB-H) group showed a significantly better OS (P = .05) than the TMB-Low (TMB-L) group. Next-generation sequencing (NGS) revealed that fibroblast growth factor receptor 2 (FGFR2) mutations positively correlated with target lesion reduction (odds ratio [OR] = 0.14; P = .02). The new regimen increased tumor-infiltration of CD8+ T and CD3+ T cells. Furthermore, a patient-derived organoid (PDO) study indicated that anlotinib could promote an immune-supportive tumor microenvironment. As conclusion, the anlotinib-toripalimab combination showed promising efficacy and favorable safety as a second-line treatment for advanced, relapsed GC/GEJC. The PD-L1 expression, TMB, and FGFR2 mutation are potential biomarkers for predicting the efficacy of this regimen (ClinicalTrials.gov registration number: NCT04713059).

Analysis of gene expression in early seed germination of rice: landscape and genetic regulation.

BACKGROUND: Seed germination is a crucial process, which determines the initiation of seed plant life cycle. The early events during this important life cycle transition that called early seed germination is defined as initially water uptake plus radicle growing out of the covering seed layers. However, a specific genome-wide analysis of early seed germination in rice is still obscure. RESULTS: In this study, the physiological characteristics of rice seed during seed germination are determined to define key points of early seed germination. Transcriptome analyses of early phase of seed germination provided deeper insight into the genetic regulation landscape. Many genes involved in starch-to-sucrose transition were differentially expressed, especially alpha-amylase 1b and beta-amylase 2, which were predominantly expressed. Differential exon usage (DEU) genes were identified, which were significantly enriched in the pathway of starch and sucrose metabolism, indicating that DEU events were critical for starch-to-sucrose transition at early seed germination. Transcription factors (TFs) were also dramatic expressed, including the abscisic acid (ABA) responsive gene, OsABI5, and gibberellic acid (GA) responsive genes, GAI. Moreover, GAI transactivated GA responsive gene, GAMYB in vivo, indicating a potential pathway involved in early seed germination process. In addition, CBL-interacting protein kinase (CIPK) genes, such as CIPK13, CIPK14 and CIPK17 were potentially interacted with other proteins, indicating its pivotal role at early seed germination. CONCLUSION: Taken together, gene regulation of early seed germination in rice was complex and protein-to-gene or protein-to-protein interactions were indispensable.

Clinicopathological characteristics and prognostic analysis of tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ (DCIS) and DCIS with microinvasion (DCIS-Mi) of the breast.

OBJECTIVE: Our purpose is to evaluate the correlation of TILs with clinicopathological characteristics and disease free survival (DFS) in DCIS and DCIS-Mi breast cancer (BC) patients. METHODS: We retrospectively reviewed the data of 360 DCIS patients and 125 DCIS-Mi patients treated by a single institution from 2016 to 2019. TILs are regarded as continuous variables and are divided into low (≤ 5%), medium (5-40%) and high (≥ 40%) for statistical analysis. RESULTS: In DCIS and DCIS-Mi patients, larger tumor size, higher nuclear grade, hormone receptor (HR) negativity and human epidermal growth factor receptor 2(HER2) overexpression are all related to high TILs (P < 0.05). In addition, compared with DCIS, DCIS-Mi patients were significantly associated with high TILs (P < 0.001). Based on the different results of the subtypes, we further studied the correlation between TILs and DFS in 279 cases of HER2+ patients (204 of DCIS; 75 of DCIS-Mi). In HER2+ group, DCIS-Mi was significantly associated with HR negativity (P = 0.015) and high TILs (P = 0.002) compared with DCIS patients. In the survival analysis, we found that TILs had no effect on the DFS of DCIS (P = 0.938), DCIS-Mi (P = 0.807), and HER2+ (P = 0.379) BC patients. In the univariate and multivariate cox regression analysis, the correlation between TILs and the prognosis of DFS has not been confirmed in the three BC groups (P > 0.05). CONCLUSION: TILs have played an non-negligible role in the progress of DCIS to DCIS-Mi, especially in HER2+ BC. The predictive and prognostic value of TILs still needs further research to confirm.

Development of a noncompetitive magnetic-phage anti-immunocomplex assay for detecting of organophosphorus pesticides with a thiophosphate group.

Organophosphorus pesticides (OPs) are widely used in agriculture and the monitoring of their residues is very important to protect human health. Immunoassays are important tools for the analysis of small molecules. Generally, noncompetitive mode of immunoassay is considered to be more sensitive than competitive mode. In this study, peptides that can identify immunocomplex of OPs were screened from a phage display library. Subsequently, a second-generation peptide library was constructed and peptides with better performance were isolated. Then, a rapid and sensitive noncompetitive magnetic-phage anti-immunocomplex assay (MPHAIA) for OPs was developed based on the best phage-peptide and single chain antibody immunomagnetic beads. The MPHAIA showed broad specificity for OPs with a thiophosphate group. The half-saturated concentration (SC50) values and limits of detection (LODs) of MPHAIA to 12 OPs were ranged from 15.04 to 105.48 ng/mL and 4.07-14.19 ng/mL, respectively. The accuracy and reliability of MPHAIA were verified by gas chromatography-tandem mass spectrometry (GC-MS/MS) parallel analysis of six kinds of OPs in spiked cucumber samples. The recovery rates were in range of 81.2-116.3% with coefficient of variation from 4.1% to 14.1%, which were consistent with the results of GC-MS/MS.

Regulation of gene expression involved in the remobilization of rice straw carbon reserves results from moderate soil drying during grain filling.

Carbon reserves in rice straw before flowering contribute greatly to grain filling. Moderate soil drying imposed at the post-anthesis stage significantly promotes carbon reserve remobilization in straws of rice, but the regulation of this process at the proteomic and transcriptomic level remains poorly understood. In this study, we applied moderate soil drying (MD) to rice at the post-anthesis stage, which was followed by dynamic proteomic and transcriptomic studies using SWATH-MS and RNA-seq analysis. MD treatment upregulated the proteins alpha-glucosidase, beta-glucosidase and starch phosphorylase, which are responsible for starch degradation. Furthermore, MD treatment enhanced the expression of proteins involved in the sucrose synthesis pathway, including SPS8 and SPP1. In addition, various monosaccharide transporters (MSTs) and sucrose transporter 2 (SUT2), which are pivotal in carbon reserve remobilization, were also upregulated in straw by MD treatment. Differentially expressed transcription factors, including GRAS, TCP, trihelix, TALE, C3H, and NF-YC, were predicted to interact with other proteins to mediate carbon reserve remobilization in response to MD treatment. Further correlation analysis revealed that the abundances of most of the differentially expressed proteins were not correlated with the corresponding transcript levels, indicating that the carbon reserve remobilization process was probably regulated by posttranscriptional modification. Our results provide insights into the molecular mechanisms underlying the regulation of carbon reserve remobilization from straw to grain in rice under MD conditions.

Apatinib in Combination with S-1 as First-Line Treatment in Patients with Advanced Metastatic Gastric Cancer: Results from an Open, Exploratory, Single-Arm, Phase II Trial.

LESSONS LEARNED: Apatinib combined with S-1 was not superior to other chemotherapy regimens as first-line therapy for advanced gastric cancer. There was a tendency for patients with lymph node metastasis to have prolonged median progression-free survival and median overall survival, compared with patients with liver metastasis. BACKGROUND: The best choice of first-line chemotherapy regimen for patients with metastatic gastric cancer is still debated. We combined apatinib and S-1 as a new first-line therapy to treat advanced gastric cancer. The efficacy and safety of the combination were assessed, with the goal of determining the most appropriate subgroup of patients who could benefit from this new regimen. METHODS: This study was an open, exploratory single-arm, phase II trial. Enrolled patients received apatinib plus S-1 treatment (apatinib, 500 mg, once a day [qd], days 1-21; S-1, 40 mg/m2 , bid, days 1-14). The primary endpoints were progression-free survival (PFS) and safety of this new regimen. Next-generation sequencing was used to explore potential biomarkers. RESULTS: A total of 30 patients were enrolled. The median progression-free survival (mPFS) was 4.21 months (95% confidence interval [CI], 2.29-6.13 months). The median overall survival (mOS) was 7.49 months (95% CI, 4.81-10.17 months). Patients with lymph node metastasis had prolonged mPFS and mOS when compared with those with liver metastasis (mPFS, 4.21 vs. 1.84 months; mOS, 8.21 vs. 6.31 months, p = .08). The most common grade 3 to 4 adverse events were abdominal pain, dizziness, and diarrhea. Gene mutation profiles between the two subgroups were significantly different. CONCLUSION: Apatinib combined with S-1 was not superior to other chemotherapy regimens as first-line therapy for advanced gastric cancer. Toxicity was consistent with known profiles when given as monotherapy. There was a tendency toward prolonged mPFS and mOS in patients with lymph node metastasis compared with patients with liver metastasis, which could support the need to design a future clinical trial with a better defined patient population.

Comparative transcriptome analysis of coleorhiza development in japonica and Indica rice.

BACKGROUND: Coleorhiza hairs, are sheath-like outgrowth organs in the seeds of Poaceae family that look like root hair but develop from the coleorhiza epidermal cells during seed imbibition. The major role of coleorhiza hair in seed germination involves facilitating water uptake and nutrient supply for seed germination. However, molecular basis of coleorhiza hair development and underlying genes and metabolic pathways during seed germination are largely unknown and need to be established. RESULTS: In this study, a comparative transcriptome analysis of coleorhiza hairs from japonica and indica rice suggested that DEGs in embryo samples from seeds with embryo in air (EIA) as compared to embryo from seeds completely covered by water (CBW) were enriched in water deprivation, abscisic acid (ABA) and auxin metabolism, carbohydrate catabolism and phosphorus metabolism in coleorhiza hairs in both cultivars. Up-regulation of key metabolic genes in ABA, auxin and dehydrin and aquaporin genes may help maintain the basic development of coleorhiza hair in japonica and indica in EIA samples during both early and late stages. Additionally, DEGs involved in glutathione metabolism and carbon metabolism are upregulated while DEGs involved in amino acid and nucleotide sugar metabolism are downregulated in EIA suggesting induction of oxidative stress-alleviating genes and less priority to primary metabolism. CONCLUSIONS: Taken together, results in this study could provide novel aspects about the molecular signaling that could be involved in coleorhiza hair development in different types of rice cultivars during seed germination and may give some hints for breeders to improve seed germination efficiency under moderate drought conditions.

OsTPP1 regulates seed germination through the crosstalk with abscisic acid in rice.

Seed germination is essential for direct seeding in rice. It has been demonstrated that trehalose-6-phosphate phosphatase 1 (OsTPP1) plays roles in improving yield and stress tolerance in rice. In this study, the roles of OsTPP1 on seed germination in rice were investigated. The tpp1 mutant germinated slower than the wild-type (WT), which can be restored by exogenous trehalose. tpp1 seeds showed higher ABA content compared with WT seeds. The tpp1 mutant was hypersensitive to ABA and ABA catabolism inhibitor (Dinicozanole). Furthermore, two ABA catabolism genes were downregulated in the tpp1 mutant which were responsible for increased ABA concentrations, and exogenous trehalose increased transcripts of ABA catabolism genes, suggesting that OsTPP1 and ABA catabolism genes acted in the same signaling pathway. Further analysis showed that a transcription factor of OsGAMYB was an activator of OsTPP1, and expression of OsGAMYB was decreased by both the exogenous and endogenous ABA, subsequently reducing the expression of OsTPP1, which suggested a new signaling pathway required for seed germination in rice. In addition, ABA-responsive genes, especially OsABI5, were invoved in OsTPP1-mediated seed germination. Overall, our study provided new pathways in seed germination that OsTPP1 controlled seed germination through crosstalk with the ABA catabolism pathway.

Analysis of Global Methylome and Gene Expression during Carbon Reserve Mobilization in Stems under Soil Drying.

In rice (Oryza sativa), a specific temporary source organ, the stem, is important for grain filling, and moderate soil drying (MD) enhanced carbon reserve flow from stems to increase grain yield. The dynamics and biological relevance of DNA methylation in carbon reserve remobilization during grain filling are unknown. Here, we generated whole-genome single-base resolution maps of the DNA methylome in the stem. During grain filling under MD, we observed an increase in DNA methylation of total cytosines, with more hypomethylated than hypermethylated regions. Genes responsible for DNA methylation and demethylation were up-regulated, suggesting that DNA methylation changes in the stem were regulated by antagonism between DNA methylation and demethylation activity. In addition, methylation in the CG and CHG contexts was negatively associated with gene expression, while that in the CHH context was positively associated with gene expression. A hypermethylated/up-regulated transcription factor of MYBS2 inhibited MYB30 expression and possibly enhanced ß-Amylase5 expression, promoting subsequent starch degradation in rice stems under MD treatment. In addition, a hypermethylated/down-regulated transcription factor of ERF24 was predicted to interact with, and thereby decrease the expression of, abscisic acid 8'-hydroxylase1, thus increasing abscisic acid concentration under MD treatment. Our findings provide insight into the DNA methylation dynamics in carbon reserve remobilization of rice stems, demonstrate that MD increased this remobilization, and suggest a link between DNA methylation and gene expression in rice stems during grain filling.

Comprehensive epigenome and transcriptome analysis of carbon reserve remobilization in indica and japonica rice stems under moderate soil drying.

Moderate soil drying (MD) imposed at the post-anthesis stage significantly improves carbon reserve remobilization in rice stems, increasing grain yield. However, the methylome and transcriptome profiles of carbon reserve remobilization under MD are obscure in indica and japonica rice stems. Here, we generated whole-genome single-base resolution maps of the DNA methylome in indica and japonica rice stems. DNA methylation levels were higher in indica than in japonica and positively correlated with genome size. MD treatment had a weak impact on the changes in methylation levels in indica. Moreover, the number of differentially methylated regions was much lower in indica, indicating the existence of cultivar-specific methylation patterns in response to MD during grain filling. The gene encoding ß-glucosidase 1, involved in the starch degradation process, was hypomethylated and up-regulated in indica, resulting in improved starch to sucrose conversion under MD treatment. Additionally, increased expression of MYBS1 transactivated the expression of AMYC2/OsAMY2A in both indica and japonica, leading to enhanced starch degradation under MD. In contrast, down-regulated expression of MYB30 resulted in increased expression of BMY5 in both cultivars. Our findings decode the dynamics of DNA methylation in indica and japonica rice stems and propose candidate genes for improving carbon reserve remobilization.

Combined indigenous yeast strains produced local wine from over ripen Cabernet Sauvignon grape in Xinjiang.

Cabernet Sauvignon grape produced in Xinjiang (China) is often overripe, with unusually high sugar content, which impedes utilization. We aimed to establish the optimal combination of indigenous yeast strains to produce a new sweet wine from the overripe grape. Five yeast strains with pronounced enological characteristics were selected from 88 indigenous yeast isolates. Using a series of co-fermentation experiments with different inoculated strategies, we achieved optimal co-fermentation with a combination of strains SC19 and NS68, later identified as Saccharomyces cerevisiae and Pichia kudriavzevii, respectively, simultaneously inoculated in a 1:1 ratio at the early stage of fermentation. The combination was characterized by vigorous fermentation with high resistance to 457.13 g/L sugar and high alcohol yield (16.01% vol). The sweet wine contained 17 aromatic compounds with odor activity value (OAV) ≥ 1 and pronounced sweet fruit, floral, herbaceous, and caramel odors. The co-fermentation has a good potential for utilization of overripe Cabernet Sauvignon grape.

Transcriptomic analysis of grain filling in rice inferior grains under moderate soil drying.

Moderate soil drying imposed at the post-anthesis stage significantly increases starch accumulation in inferior grains of rice, but how this process is regulated at the level of gene expression remains unclear. In this study, we applied moderate drying (MD) treatments to the soil at the post-anthesis stage and followed the dynamics of the conversion process of soluble sugars to starch in inferior grains using RNA-seq analysis. An elevated level of ABA induced by MD was consistently associated with down-regulation of ABA8ox2, suggesting that lower expression of this gene may be responsible for the higher ABA content, potentially resulting in better filling in inferior grains. In addition, MD treatments up-regulated genes encoding five key enzymes involved sucrose-to-starch conversion and increased the activities of enzymes responsible for soluble-sugar reduction and starch accumulation in inferior grains. Differentially expressed transcription factors, including NAC, GATA, WRKY, and M-type MADS, were predicted to interact with other proteins in mediating filling of inferior grains as a response to MD. Transient expression analysis showed that NAC activated WAXY expression by binding to its promoter, indicating that NAC played a key role in starch synthesis of inferior grains under MD treatment. Our results provide new insights into the molecular mechanisms that regulate grain filling in inferior grains of rice under moderate soil drying.

Regulation of Gene Expression in the Remobilization of Carbon Reserves in Rice Stems During Grain Filling.

Carbon reserves in rice straw (stem and sheath) before flowering contribute to a significant portion of grain filling. However, the molecular mechanism of carbon reserve remobilization from straw to grains remains unclear. In this study, super rice LYP9 and conventional rice 9311 showed different carbon reserve remobilization behaviors. The transcriptomic profiles of straws of LYP9 and 9311 were analyzed at three stages of grain filling. Among the differentially expressed genes (DGs), 5,733 genes were uniquely up- or down-regulated at 30 days after anthesis (DAA) between LYP9 and 9311 in comparison with 681 at 10 DAA and 495 at 20 DAA, suggesting that the gene expression profile of LYP9 was very different from that of 9311 at the late stage of grain filling. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Ontology (GO) classification of DGs both showed that the carbohydrate catabolic pathway, plant hormone signal transduction and photosynthesis pathway were enriched in DGs, suggesting their roles in carbon reserve remobilization, which explains to a certain extent the difference in non-structural carbohydrate content, photosynthesis and ABA content between the two cultivars during grain filling. Further comparative analysis and confirmation by quantitative real-time PCR and enzyme assays suggest that genes involved in trehalose synthesis (trehalose-phosphate phosphatase and trehalose 6-phosphate synthase/phosphatase), starch degradation (ß-amylase) and sucrose synthesis (sucrose-phosphate synthase and sucrose synthase) were important for carbon reserve remobilization, whereas ABA content was determined by the counteraction of NCED1 and ABA8ox1 genes. The higher expression level of all these genes and ABA content in 9311 resulted in better efficiency of carbon reserve remobilization in 9311 than in LYP9.

Case report: A rare immune-related adverse effect: hepatic cavernous hemangioma induced by camrelizumab.

Background: Camrelizumab, a programmed death 1 (PD-1) inhibiting antibody, has demonstrated efficacy in various malignancies and received approval in multiple countries. Despite its therapeutic benefits, camrelizumab is associated with a unique spectrum of immune-related adverse effects (irAEs), predominantly reactive cutaneous capillary endothelial proliferation (RCCEP). However, visceral manifestations of such endothelial proliferations, particularly hepatic cavernous hemangiomas, have not been extensively documented. Methods: This case series retrospectively reviews six patients who developed hepatic hemangiomas following treatment with camrelizumab in combination with other chemotherapeutic agents. The series highlights the clinical course, imaging findings, management strategies, and outcomes associated with this complication. A detailed analysis was conducted to discern the potential causal relationship between camrelizumab therapy and the development of hepatic hemangiomas. Results: All six patients, after varying cycles of camrelizumab-based therapy, presented with hepatic lesions identified as cavernous hemangiomas on imaging. These findings were atypical for metastatic disease and were further complicated by significant clinical events, including massive intra-abdominal bleeding post-biopsy. Discontinuation of camrelizumab led to a reduction in the size of the hemangiomas in two cases, suggesting a potential link between the drug and the development of these vascular lesions. The incidence of RCCEP remained high, and the use of other agents such as bevacizumab did not mitigate the occurrence of hepatic hemangiomas, indicating a possible unique pathogenic mechanism associated with camrelizumab. Conclusion: Hepatic cavernous hemangioma may represent a rare but clinically significant irAE associated with camrelizumab therapy. This series underscores the importance of vigilant monitoring and a high index of suspicion for atypical hepatic lesions in patients undergoing treatment with PD-1 inhibitors. Further studies are warranted to elucidate the pathophysiology of this complication and to establish guidelines for the management and surveillance of patients receiving camrelizumab.

Clinical practice guideline for acupuncture and moxibustion: Female urinary incontinence.

Urinary incontinence (UI) is a common problem worldwide. It has a major impact on physical and social activities and interpersonal relationships. UI is common in women, but is under-reported and under-treated. It affects the quality of life of female patients severely. Acupuncture and moxibustion have been proposed as potentially effective interventions for female UI. Hence, for the benefit of acupuncture practitioners around the world, the World Federation of Acupuncture-moxibustion Societies initiated a project to develop a clinical practice guideline (CPG) for the use of acupuncture and moxibustion to treat female UI. This CPG was developed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, referring to the principles of the World Health Organization Handbook for Guideline Development. During the development of the CPG, the guideline development group (GDG) played an important role. The clinical questions, recommendations and therapeutic protocols were all formulated by GDG using the modified Delphi method. This CPG contains ten recommendations about the use of acupuncture and moxibustion interventions for ten clinical questions, which include nine conditional recommendations for the intervention and one conditional recommendation for either the intervention or the comparison. This CPG also provides one protocol for conventional filiform needle therapy, two therapy protocols for deep needling stimulation on lumbosacral acupoints, and four moxibustion therapy protocols, based on the protocols presented in randomized controlled trials reviewed by the GDG. Please cite this article as: Yang C, Wang SZ, Chen S, Du S, Wang GQ, Guo W, Xie XL, Peng BH, Du SH, Zhao JP. Clinical practice guideline for acupuncture and moxibustion: Female urinary incontinence. J Integr Med. 2024; 22(3): 258-269.

Clinical practice guideline for acupuncture and moxibustion: Allergic rhinitis.

Acupuncture is one of the most effective complementary therapies for allergic rhinitis (AR) and has been recommended by several clinical practice guidelines (CPGs) for AR. However, these CPGs mentioned acupuncture without making recommendations for clinical implementation and therapeutic protocols, therefore limiting the applicability of acupuncture therapies for AR. Hence, for the benefit of acupuncture practitioners around the world, the World Federation of Acupuncture-moxibustion Societies have initiated a project to develop the CPG for the use of acupuncture and moxibustion to treat AR. This CPG was developed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, referring to the principles of the World Health Organization Handbook for Guideline Development. During the development of the CPG, the guideline development group (GDG) played an important role. The clinical questions, recommendations and therapeutic protocols were all formulated by the GDG using the modified Delphi method. The CPG contains recommendations for 15 clinical questions about the use of acupuncture and moxibustion interventions. These include one strong recommendation for the intervention based on high-quality evidence, three conditional recommendations for either the intervention or standard care, and 11 conditional recommendations for the intervention based on very low quality of evidence. The CPG also provides one filiform needle acupuncture protocol and five moxibustion protocols extracted based on the protocols presented in randomized controlled trials reviewed by the GDG. Please cite this article as: Du SH, Chen S, Wang SZ, Wang GQ, Du S, Guo W, Xie XL, Peng BH, Yang C, Zhao JP. Clinical practice guideline for acupuncture and moxibustion: Allergic rhinitis. J Integr Med. 2024; 22(3): 245-257.