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Abstract Background Organoid technology is an emerging and rapidly growing field that shows promise in studying organ development and screening therapeutic regimens. Although organoids have been proposed for a decade, concerns exist, including batch‐to‐batch variations, lack of the native microenvironment and clinical applicability. Main body The concept of organoids has derived patient‐derived tumour organoids (PDTOs) for personalized drug screening and new drug discovery, mitigating the risks of medication misuse. The greater the similarity between the PDTOs and the primary tumours, the more influential the model will be. Recently, ‘tumour assembloids’ inspired by cell‐coculture technology have attracted attention to complement the current PDTO technology. High‐quality PDTOs must reassemble critical components, including multiple cell types, tumour matrix, paracrine factors, angiogenesis and microorganisms. This review begins with a brief overview of the history of organoids and PDTOs, followed by the current approaches for generating PDTOs and tumour assembloids. Personalized drug screening has been practised; however, it remains unclear whether PDTOs can predict immunotherapies, including immune drugs (e.g. immune checkpoint inhibitors) and immune cells (e.g. tumour‐infiltrating lymphocyte, T cell receptor‐engineered T cell and chimeric antigen receptor‐T cell). PDTOs, as cancer avatars of the patients, can be expanded and stored to form a biobank. Conclusion Fundamental research and clinical trials are ongoing, and the intention is to use these models to replace animals. Pre‐clinical immunotherapy screening using PDTOs will be beneficial to cancer patients. Key Points The current PDTO models have not yet constructed key cellular and non‐cellular components. PDTOs should be expandable and editable. PDTOs are promising preclinical models for immunotherapy unless mature PDTOs can be established. PDTO biobanks with consensual standards are urgently needed.

Liuzhou river snail rice noodle is a local characteristic food of Liuzhou with fresh, spicy, sour and “smelly”. With the rapid development of pre-packaged river snail rice noodle, the concerns such as unstable quality and inconsistent standards have begun to emerge. The quality and unique flavor of Liuzhou river snail rice noodle are closely related to the flavor substances of its raw materials. The detection and analysis of its flavor substances is one of the key factors to measure the quality of river snail rice noodle. In this paper, based on the features of flavor substances of raw materials such as snails, sour bamboo shoots and chili oil in Liuzhou snail powder, the sources of its flavor substances were reviewed mainly according to the current research on river snail rice noodle and the related techniques of flavor substances detection. The effects of flavor substances of raw materials and excipients were systematically expounded. The development prospect of common detection techniques of flavor substances in the analysis of flavor substances and the key flavor substances of raw materials and excipients were further reviewed. The disadvantages of the research on the flavor substances of were pointed out, and the future research direction of its flavor substances was put forward, aming to provide theoretical support for the improvement, standardization and development of new products of Liuzhou river snail rice noodle.

Abstract The gut microbiota may have an effect on the therapeutic resistance and toxicity of immune checkpoint inhibitors (ICIs). However, the associations between the highly variable genomes of gut bacteria and the effectiveness of ICIs remain unclear, despite the fact that merely a few gene mutations between similar bacterial strains may cause significant phenotypic variations. Here, using datasets from the gut microbiome of 996 patients from seven clinical trials, we systematically identify microbial genomic structural variants (SVs) using SGV-Finder. The associations between SVs and response, progression-free survival, overall survival, and immune-related adverse events are systematically explored by metagenome-wide association analysis and replicated in different cohorts. Associated SVs are located in multiple species, including Akkermansia muciniphila, Dorea formicigenerans, and Bacteroides caccae. We find genes that encode enzymes that participate in glucose metabolism be harbored in these associated regions. This work uncovers a nascent layer of gut microbiome heterogeneity that is correlated with hosts’ prognosis following ICI treatment and represents an advance in our knowledge of the intricate relationships between microbiota and tumor immunotherapy.

Study region: Longchuan River Basin in the Hengduan mountain region, China. Study focus: With the decrease in annual precipitation, the sediment yield on the slope and sediment delivery ratio (SDR) in the river channel, both play a critical role in runoff and sediment load change. However, the response mechanism of SDR to climate change and human activities remains unclear. The RUSLE model was used to calculate the sediment yield on the slope, and the SDR is quantified by the ratio of sediment load in the channel to the sediment yield on the slope.New hydrological insights for the region: Under climate change, the reduced annual rainfall caused a significant decrease in annual runoff and sediment load in the Longchuan River Basin (LRB), since 2003. The RUSLE model was used to calculate the sediment yield on the slope in LRB, and the sediment delivery ratio (SDR) was calculated by the ratio of sediment load to sediment yield. We found a new approach relevant to the relationship of SDR with annual runoff and sediment yield, which can indicate the response mechanism of SDR to climate change. In anthropogenic activities, reservoir interception is the main reason for the sediment load reduction, instead of the land use and land cover change. With a large reservoir built in the LRB, the average SDR is reduced by 83.04 % and the average trap efficiency of the reservoir is 0.96, which was calculated by the Brune equation. This study provides a feasible method to evaluate the effect of different factors on the runoff and sediment load change in the basin.

Abstract Minimal change disease (MCD) is the common type of nephrotic syndrome (NS) in children. Currently, there is an urgent need to explore new treatments because of the significant side effects of long-term use of glucocorticoids and immunosuppressive drugs and the failure to reduce proteinuria in some patients. Angiopoietin-like protein 3 (Angptl3) is an essential target of NS, and anti-ANGPTL3-FLD monoclonal antibody (mAb) significantly reduces proteinuria in mice with adriamycin nephropathy (AN). However, some proteinuria is persistent. Minnelide, a water-soluble prodrug of triptolide, has been used for the treatment of glomerular disease. Therefore, the present study aimed to investigate whether minnelide combined with mAb could further protect mice with AN and the underlying mechanisms. 8-week-old C57BL/6 female mice were injected with 25 mg/kg of Adriamycin (ADR) by tail vein to establish the AN model. A dose of 200 μg/kg of minnelide or 20 mg/kg of mAb was administered intraperitoneally for the treatment. In vitro, the podocytes were treated with 0.4 μg/mL of ADR for 24 h to induce podocyte injury, and pretreatment with 10 ng/mL of triptolide for 30 min or 100 ng/mL of mAb for 1 h before ADR exposure was used to treat. The results showed that minnelide combined with mAb almost completely ameliorates proteinuria and restores the ultrastructure of the podocytes in mice with AN. In addition, minnelide combined with mAb restores the distribution of Nephrin, Podocin, and CD2AP and reduces the level of inflammatory factors in mice with AN. Mechanistically, minnelide combined with mAb could further alleviate apoptosis and promote autophagy in mice with AN by inhibiting the mTOR signaling pathway. In vitro, triptolide combined with mAb increases the expression of Nephrin, Podocin, and CD2AP, alleviates apoptosis, and promotes autophagy. Overall, minnelide combined with mAb completely protects the mice with AN by promoting autophagy and inhibiting apoptosis.

Drug-induced liver injury (DILI) is one of the serious adverse drug reactions (ADRs), which belongs to immune-mediated adverse drug reactions (IM-ADRs). As an essential health drug, albendazole has rarely been reported to cause serious liver damage. A young man in his 30 s developed severe jaundice, abnormal transaminases, and poor blood coagulation mechanism after taking albendazole, and eventually developed into severe liver failure. The patient was found heterozygous of HLA-B*15:02 and HLA-B*13:01 through HLA-targeted sequencing, which may have a pathogenic role in the disease. This case report summarizes his presentation, treatment, and prognosis. A useful summary of the diagnosis and associated genetic variant information is provided.

Abstract Background Radiotherapy (RT) is the standard treatment for nasopharyngeal carcinoma (NPC). However, due to individual differences in radiosensitivity, biomarkers are needed to tailored radiotherapy to cancer patients. However, comprehensive genome-wide radiogenomic studies on them are still lacking. The aim of this study was to identify genetic variants associated with radiotherapy response in patients with NPC. Methods This was a large‑scale genome-wide association analysis (GWAS) including a total of 981 patients. 319 individuals in the discovery stage were genotyped for 688,783 SNPs using whole genome-wide screening microarray. Significant loci were further genotyped using MassARRAY system and TaqMan SNP assays in the validation stages of 847 patients. This study used logistic regression analysis and multiple bioinformatics tools such as PLINK, LocusZoom, LDBlockShow, GTEx, Pancan-meQTL and FUMA to examine genetic variants associated with radiotherapy efficacy in NPC. Results After genome-wide level analysis, 19 SNPs entered the validation stage (P

The study sought to establish a sensitive and specific on-site loop-mediated isothermal amplification (LAMP) for Brucella heated using a warmer pad. LAMP primers specific to the conserved BvrR gene were designed, and the LAMP reaction was optimized. The heating characteristics of the warmer pad were investigated. The detection validity (specificity, sensitivity) of clinical samples by warmer-pad LAMP (WP-LAMP) was compared with that of qPCR. The WP-LAMP method displayed high specificity and sensitivity for five Brucella gene copies. The detection of 104 clinical samples was 97.1% concordant with quantitative polymerase chain reaction. The results showed the success of the WP-LAMP for on-site detection. The method requires no special equipment and is conducive to the prevention and control of brucellosis.

Abstract Background Genetic variants associated with acute side effects of radiotherapy in nasopharyngeal carcinoma (NPC) remain largely unknown. Methods We performed a two-stage genome-wide association analysis including a total of 1084 patients, where 319 individuals in the discovery stage were genotyped for 688,783 SNPs using whole genome-wide screening microarray. Significant variants were then validated in an independent cohort of 765 patients using the MassARRAY system. Gene mapping, linkage disequilibrium, genome-wide association analysis, and polygenic risk score were conducted or calculated using FUMA, LDBlockShow, PLINK, and PRSice software programs, respectively. Results Five SNPs (rs6711678, rs4848597, rs4848598, rs2091255, and rs584547) showed statistical significance after validation. Radiotherapy toxicity was more serious in mutant minor allele carriers of all five SNPs. Stratified analysis further indicated that rs6711678, rs4848597, rs4848598, and rs2091255 correlated with skin toxicity in patients of EBV positive, late stage (III and IV), receiving both concurrent chemoradiotherapy and induction/adjuvant chemotherapy, and with OR values ranging from 1.92 to 2.66. For rs584547, high occurrence of dysphagia was found in A allele carriers in both the discovery (P = 1.27 × 10− 6, OR = 1.55) and validation (P = 0.002, OR = 4.20) cohorts. Furthermore, prediction models integrating both genetic and clinical factors for skin reaction and dysphagia were established. The area under curve (AUC) value of receiver operating characteristic (ROC) curves were 0.657 (skin reaction) and 0.788 (dysphagia). Conclusions Rs6711678, rs4848597, rs4848598, and rs2091255 on chromosome 2q14.2 and rs584547 were found to be novel risk loci for skin toxicity and dysphagia in NPC patients receiving radiotherapy. Trial registration Chinese Clinical Trial Register (registration number: ChiCTR-OPC-14005257 and CTXY-140007-2).

Abstract The tumor microenvironment (TME) is essential for immune escape by tumor cells. It plays essential roles in tumor development and metastasis. The clinical outcomes of tumors are often closely related to individual differences in the patient TME. Therefore, reprogramming TME cells and their intercellular communication is an attractive and promising strategy for cancer therapy. TME cells consist of immune and nonimmune cells. These cells need to be manipulated precisely and safely to improve cancer therapy. Furthermore, it is encouraging that this field has rapidly developed in recent years with the advent and development of gene editing technologies. In this review, we briefly introduce gene editing technologies and systematically summarize their applications in the TME for precision cancer therapy, including the reprogramming of TME cells and their intercellular communication. TME cell reprogramming can regulate cell differentiation, proliferation, and function. Moreover, reprogramming the intercellular communication of TME cells can optimize immune infiltration and the specific recognition of tumor cells by immune cells. Thus, gene editing will pave the way for further breakthroughs in precision cancer therapy.

Sex chromosomes evolved from autosomes many times across the eukaryote phylogeny. Several models have been proposed to explain this transition, some involving male and female sterility mutations linked in a region of suppressed recombination between X and Y (or Z/W, U/V) chromosomes. Comparative and experimental analysis of a reference genome assembly for a double haploid YY male garden asparagus (Asparagus officinalis L.) individual implicates separate but linked genes as responsible for sex determination. Dioecy has evolved recently within Asparagus and sex chromosomes are cytogenetically identical with the Y, harboring a megabase segment that is missing from the X. We show that deletion of this entire region results in a male-to-female conversion, whereas loss of a single suppressor of female development drives male-to-hermaphrodite conversion. A single copy anther-specific gene with a male sterile Arabidopsis knockout phenotype is also in the Y-specific region, supporting a two-gene model for sex chromosome evolution.