T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Persistent Organic Pollutants (POPs) have the characteristics of resistance to environmental degradation, bioaccumulation and long-distance migration potential. Maternal exposure to POPs during pregnancy can enter the fetal blood circulation through the placental barrier, and have a potential impact on the functional development of the nervous system of the offspring. This in turn leads to the occurrence and development of neurological defects and diseases in adulthood. The purpose of this paper is to elucidate the effects of exposure to three major POPs (organochlorine compounds, perfluoroalkyl and polyfluoroalkyl substances, and polybrominated diphenyl ethers) during pregnancy on the functional development of the nervous system (social emotions, cognition, language, exercise, and adaptability) in children, and to provide reference for subsequent studies.

Objective To compare the differences in lipid metabolism between platinum-resistant and platinum-sensitive ovarian cancer patients at stage Ⅲ-Ⅳ,to analyze the differential intestinal flora using 16S rRNA sequen-cing,and to explore the associations among intestinal flora,lipid metabolism characteristics and platinum resistance in ovarian cancer.Methods Patients diagnosed with ovarian cancer at stage Ⅲ-Ⅳ through surgical pathology were selected,including a platinum-resistant group(11 cases)and a platinum-sensitive group(11 cases).The differences in lipid metabolism between the two groups were compared.The differences in gut microbiota between the two groups were investigated using fecal 16S rRNA sequencing.The association among gut microbiota,lipid metabolism characteristics,and platinum resistance in ovarian cancer was analyzed.Results Significant differ-ences were observed in lipid metabolism-related indicators[total cholesterol(TC),high-density lipoprotein choles-terol(HDL-C),non-high-density lipoprotein cholesterol(n-HDL),low-density lipoprotein cholesterol(LDL-C),apolipoprotein(B)]between the two groups,with higher levels in the platinum-resistant group.The Shannon in-dex(P=0.008 3)and Simpson index(P=0.008 2)both showed higher diversity of gut microbiota in platinum-resistant ovarian cancer patients compared to the platinum-sensitive group.However,based on OTUs species clus-tering and relative abundance statistics,certain bacterial abundances differed significantly between the groups.Spe-cies such as Parabacteroides,Akkermansia,Blautia,Lachnoclostridium,Fusicatenibacter,and Megamonas had sig-nificantly higher abundances in the platinum-sensitive ovarian cancer group,and Akkermansia(a lipid metabolism-related bacterial group)was the most prevalent.Conclusion The platinum-resistant group of ovarian cancer ex-hibits significantly higher levels of lipid metabolism and gut microbiota diversity compared to the platinum-sensitive group.This suggests that the increase in lipid metabolism levels and fecal microbiota diversity may be associated with the development of platinum resistance.However,certain microbial taxa are reduced in abundance in the plat-inum-resistant group,such as the distinct Akkermansia genus(a lipid metabolism-related microbial community),which may serve as one of the factors inducing platinum-resistance in ovarian cancer.

Persistent Organic Pollutants (POPs) have the characteristics of resistance to environmental degradation, bioaccumulation and long-distance migration potential. Maternal exposure to POPs during pregnancy can enter the fetal blood circulation through the placental barrier, and have a potential impact on the functional development of the nervous system of the offspring. This in turn leads to the occurrence and development of neurological defects and diseases in adulthood. The purpose of this paper is to elucidate the effects of exposure to three major POPs (organochlorine compounds, perfluoroalkyl and polyfluoroalkyl substances, and polybrominated diphenyl ethers) during pregnancy on the functional development of the nervous system (social emotions, cognition, language, exercise, and adaptability) in children, and to provide reference for subsequent studies.

Objective:To summarize the single-center experience of serial transverse enteroplasty (STEP) in children with intestinal failure.Methods:The clinical data of 13 children who underwent STEP surgery at our department from Jan 2016 to Dec 2022 was retrospectively analyzed.Results:Eight children were females ,5 were males. There were 10 premature infants and 3 full-term infants. The gestational age was 26 +3-39 +5 weeks, and the birth weight was 860 -3 700 g. The median age of surgery was 12 months, the median length of small intestine was 70 (50-130) cm, the diameter of preoperative intestinal dilation was about 4.5 to 7.5 cm, and the operation interval was 2.5 to 3.0 cm. Continuous transverse enteroenteroplasty resulted in an average increase of 75% (66% to 100%) in the length of the dilated intestinal segment. The total length of the small intestine increases by 16.0% (12.5%-30.0%). After the operation, 12 of the 13 children (92.3%) were removed from parenteral nutrition to achieve intestinal adaptation of the remaining bowel, and the mean time of withdrawal from parenteral nutrition was 138(20-1 011) days after the operation. Intestinal dilatation occurred in 2 patients, and gastrointestinal bleeding occurred in 4 patients, which healed after conservative treatment. Conclusions:STEP operation is suitable for children with short intestinal length and obvious expansion of intestinal tube. STEP can not only reduce the diameter of the enlarged intestine, but also extend the length of the intestine, increase the feeding tolerance, improve the clinical effect of enteral nutrition, and shorten the time for children to achieve intestinal adaptation.

OBJECTIVE: To explore the genetic basis for two patients from a family with BCL11A-related intellectual disability (BCL11A-ID). METHODS: Clinical data of the proband and her family members was analyzed. Chromosomal karyotyping analysis, trio-whole exome sequencing (trio-WES) and copy number variation sequencing (CNV-seq) were carried out. For the suspected genetic variants, Sanger sequencing was used to verify, and pathogenicity assessment was conducted. RESULTS: The proband and her mother both had intellectual and language impairment, and their fetal hemoglobin (HbF) was significantly elevated. A heterozygous c.1327_c.1328delTC (p.Ser443Hisfs*128) variant was found in exon 4 of the BCL11A gene by WES, which has resulted in truncated expression of the encoded protein, and Sanger sequencing has verified that the variant was inherited from the mother. The variant was not found in related databases. The variant was predicted as pathogenic according to the guidelines from the American College of Medical Genetics and Genomics (ACMG) (PVS1+PM2+PP1). No karyotypic abnormality was found in the proband, her parents and brother, and no pathogenic CNVs was found in the proband and her parents. CONCLUSION The c.1327_c.1328delTC (p.Ser443Hisfs*128) variant may underlay the BCL11A-ID in the proband and her mother. This de novo variant has expanded the mutational spectrum of the BCL11A gene.
Humans ; Male ; Female ; Intellectual Disability/genetics* ; DNA Copy Number Variations ; Pedigree ; Mutation ; Transcription Factors/genetics* ; Mothers ; Repressor Proteins/genetics*

Peribiliary glands (PBG) is a kind of microscopic structure around the intra-hepatic bile ducts and extrahepatic bile ducts. PBG not only participates in maintaining the normal physiological function of biliary epithelial tissue, but also plays an important role in its damage and repair process. Biliary tree stem/progenitor cells in PBG are important cell sources of biliary epithelial regeneration and repair. PBG and the surrounding peribiliary vascular plexus are key influencing factors for the occurrence of ischemic-type biliary lesions (ITBL) after liver transplantation. Based on relevant literatures and clinical practice, the authors summarize the function of PBG as well as its relationship with ITBL.

The fall armyworm (FAW), Spodoptera frugiperda, is a destructive pest native to America and has recently become an invasive insect pest in China. Because of its rapid spread and great risks in China, understanding of FAW genetic background and pesticide resistance is urgent and essential to develop effective management strategies. Here, we assembled a chromosome-level genome of a male FAW (SFynMstLFR) and compared re-sequencing results of the populations from America, Africa, and China. Strain identification of 163 individuals collected from America, Africa and China showed that both C and R strains were found in the American populations, while only C strain was found in the Chinese and African populations. Moreover, population genomics analysis showed that populations from Africa and China have close relationship with significantly genetic differentiation from American populations. Taken together, FAWs invaded into China were most likely originated from Africa. Comparative genomics analysis displayed that the cytochrome p450 gene family is extremely expanded to 425 members in FAW, of which 283 genes are specific to FAW. Treatments of Chinese populations with twenty-three pesticides showed the variant patterns of transcriptome profiles, and several detoxification genes such as AOX, UGT and GST specially responded to the pesticides. These findings will be useful in developing effective strategies for management of FAW in China and other invaded areas.
Animals ; China ; Genomics ; Humans ; Male ; Pesticides ; Spodoptera/genetics* ; Transcriptome

Helicobacter pylori (H. pylori), creating a global infection rate over 50%, presents great challenges in clinical therapies due to its complex pathological microenvironment in vivo. To improve the eradication efficacy, herein we fabricated a pharmaceutical vesicle RHL/Cl-Ch-cal where cholesterol-PEG, calcitriol and first-line antibiotic clarithromycin were co-loaded in the rhamnolipid-composed outer lipid layer. RHL/Cl-Ch-cal could quickly penetrate through gastric mucus layer to reach H. pylori infection sites, and then effectively destroyed the architecture of H. pylori biofilms, killed dispersed H. pylori and inhibited the re-adhesion of residual bacteria (called biofilms eradication tetralogy). Moreover, RHL/Cl-Ch-cal activated the host immune response to H. pylori by replenishing cholesterol to repair lipid raft on the cell membrane of host epithelial cells. Finally, RHL/Cl-Ch-cal killed the intracellular H. pylori through recovering the lysosomal acidification and assisting degradation. In experiments, RHL/Cl-Ch-cal demonstrated prominent anti-H. pylori efficacy in the classical H. pylori-infected mice model. Therefore, the study provides a "comprehensive attack" strategy for anti-H. pylori therapies including biofilms eradication tetralogy, immune activation and intracellular bacteria killing.

Objective:To explore the feasibility of technological modification and innovation of full-left/full-right liver splitting in situ for donors and examine the safety of clinical application for liver transplantation (LT).Methods:From March 2021 to June 2022, clinical and surgical data are retrospectively reviewed for 27 donors undergoing full-left/full-right liver splitting in situ and the corresponding 49 recipients undergoing full-left/full-right LT.According to the split liver technique used in donor liver surgery, they are divided into conventional split group(group A, 13 cases)and innovative split group(group B, 14 cases). The corresponding recipients are divided into two groups of recipient C(25 cases)and recipient D(24 cases). General profiles, intraoperative findings, type of vascular allocation and short-term outcomes in two groups are compared.After full-size split liver transplantation(fSLT), follow-ups continued until the end of September 2022.Results:There are 23 males and 4 females in donors.The causes of mortality for donors are traumatic head injury(12 cases)cerebrovascular accident(13 cases)and anoxia encephalopathy(2 cases). Baseline characteristics of two groups indicate that body weight and body mass index(BMI)are higher in group B and blood sodium level is lower than that in group A( P<0.05). No statistical differences exist for the others.Liver splitting time is significantly shorter in group B than that in group A(175 vs.230 min, P=0.022). No significant inter-group difference exists in type of vascular allocation.Retrohepatic inferior vena cava(IVC)is split in one case in group A and 10 cases in group B( P=0.001). Among 20 cases of right hemiliver requiring a reconstruction of segment Ⅴ/Ⅷ venous outflow, 12 cases in group A and 3 cases in group B are reconstructed with conventional independent bridging method(independent type)while another 5 cases in group B reconstruct with innovated technique by bridging Ⅴ/Ⅷ vein for splitting IVC with iliac vessel and molding all outflows as one for anastomosis(combined typ e). There is significant inter-group difference( P=0.004). No significant differences exist in operative duration, anhepatic phase or blood loss between groups C and B, except for T tube retaining in 7 cases of group A and 14 cases of group D( P=0.032). Twelve cases developed a total of 26 instances of≥Clavien-Dindo grade Ⅲ complications.Of which, 7 cases in group C and 5 cases in group D show no significant difference in postoperative morbidity.However, for serious biliary complications(≥Clavien Dindo grade Ⅲ), there are 6 cases in group C versus none in group D( P=0.016). Two cases died from postoperative complication with a postoperative mortality rate of 4.1%.Postoperative hospital stay is similar in two groups.And accumulates 6/12-month survivals were 95.9% and 87.7% for grafts and 95.9% and 92.4% for recipients respectively. Conclusions:Operative duration of full-left/full-right liver splitting in situ tends to shorten with an accumulation of a certain amount of cases.Technological modification and innovation in IVC splitting and segment Ⅴ/Ⅷ vein reconstruction should be further validated as both feasible and safe by short-term outcomes of the corresponding recipients.