Association between Pre-operative Body Mass Index and Surgical Infection in Perihilar Cholangiocarcinoma Patients Treated with Curative Resection: A Multi-center Study.

Background: The objective of this study was to investigate the association between pre-operative body mass index (BMI) and surgical infection in perihilar cholangiocarcinoma (pCCA) patients treated with curative resection. Methods: Consecutive pCCA patients were enrolled from four tertiary hospitals between 2008 and 2022. According to pre-operative BMI, the patients were divided into three groups: low BMI (≤18.4 kg/m2), normal BMI (18.5-24.9 kg/m2), and high BMI (≥25.0 kg/m2). The incidence of surgical infection among the three groups was compared. Multivariable logistic regression models were used to determine the independent risk factors associated with surgical infection. Results: A total of 371 patients were enrolled, including 283 patients (76.3%) in the normal BMI group, 30 patients (8.1%) in the low BMI group, and 58 patients (15.6%) in the high BMI group. The incidence of surgical infection was significantly higher in the patients in the low BMI and high BMI groups than in the normal BMI group. The multivariable logistic regression model showed that low BMI and high BMI were independently associated with the occurrence of surgical infection. Conclusions: The pCCA patients with a normal BMI treated with curative resection could have a lower risk of surgical infection than pCCA patients with an abnormal BMI.

Long-term prognosis of patients with gallbladder carcinoma after curative-intent resection based on changes in the ratio of carbohydrate antigen 19-9 to total bilirubin (CA19-9/TB): a multicenter retrospective cohort study.

BACKGROUND: The prognostic value of carbohydrate antigen 19-9 (CA19-9) is known to be affected by elevated bilirubin levels in patients with gallbladder carcinoma (GBC). The clinical significance of changes in the ratio of CA19-9 levels to total bilirubin (TB) levels in patients with GBC after curative-intent resection remains unknown. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative CA19-9/TB ratio in these patients. METHODS: Prospectively collected data on consecutive patients who underwent curative-intent resection for GBC between January 2015 and December 2020 stored in a multicenter database from 10 hospitals were analyzed in this retrospective cohort study. Based on the adjusted CA19-9 defined as the ratio of CA19-9 to TB, and using 2×10 3  U/µmol as the upper normal value, patients were divided into a normal group (with normal preoperative and postoperative adjusted CA19-9), a normalization group (with abnormal preoperative but normal postoperative adjusted CA19-9), and a non-normalization group (with abnormal postoperative adjusted CA19-9). The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). The log-rank test was used to compare OS and RFS among the groups. The Cox regression model was used to determine factors independently associated with OS and RFS. RESULTS: The normal group ( n =179 patients) and the normalization group ( n =73 patients) had better OS and RFS than the non-normalization group ( n =65 patients) (the 3-year OS rates 72.0%, 58.4% and 24.2%, respectively; the RFS rates 54.5%, 25.5% and 11.8%, respectively; both P <0.001). There were no significant differences between the normal and the normalization groups in OS and RFS (OS, P =0.255; RFS, P =0.130). Cox regression analysis confirmed that the non-normalization group was independently associated with worse OS and RFS. Subgroup analysis revealed that the non-normalization group of patients who received adjuvant therapy had significantly improved OS and RFS as compared to those who did not receive adjuvant therapy (OS, P =0.025; RFS, P =0.003). CONCLUSIONS: Patients with GBC who underwent curative-intent surgical resection with postoperative abnormal levels of adjusted CA19-9 (the CA19-9/TB ratio) were associated with poorer long-term survival outcomes. Adjuvant therapy after surgery improved the long-term outcomes of these patients.

Yeast mediates the interspecific interaction between introduced Bactrocera dorsalis and indigenous Bactrocera minax.

BACKGROUND: Host plant-microbe associations mediate interspecific interactions amongst herbivorous insects. However, this theory has rarely been ecologically verified in tephritid fruit flies. Research on this subject can not only help predict tephritid species invasion and occurrence patterns, but also develop potential novel lures for the control of the tephritid fruit fly pests. Recently, we observed mixed infestation of Bactrocera minax and Bactrocera dorsalis larvae in citrus orchards, which prompted us to explore the underlying mechanism. RESULTS: Following oviposition by B. minax, the yeast Pichia kluyveri translocated to and proliferated inside the citrus fruit. The level of d-limonene released from citrus fruits containing P. kluyveri was 27 times higher than that released from healthy fruits. Mature B. dorsalis females were attracted to d-limonene and oviposited into fruits previously infested by B. minax. Furthermore, the interspecific interaction between B. dorsalis and B. minax within the same fruit significantly decreased the number of surviving larvae and pupal weight in B. dorsalis, but its effect on B. minax was weaker. CONCLUSION: In the studied interspecific interaction, B. minax occupies the dominant position, implying ecological significance for this species in terms of consolidating its own niche and inhibiting the invasion of exotic species. To our best knowledge, this is the first report from both ecological and physiological perspectives on a symbiotic yeast mediating the interaction between B. minax and B. dorsalis through altering fruit volatiles. © 2022 Society of Chemical Industry.

The lifestyle of Tuyuhun royal descendants: Identification and chemical analysis of buried plants in the Chashancun cemetery, northwest China.

The Tuyuhun Kingdom (AD 313-663) was one of the most famous regimes in northwest China during the early medieval period. However, the lifestyle and spiritual pursuit of their descendants who became allied with the Tang Dynasty remain enigmatic. The excavation of the Chashancun cemetery, a Tuyuhun royal descendant (AD 691) cemetery in the Qilian Mountains in northwest China, reveals a large amount of uncharred plant remains. These remains provided a rare opportunity to explore the geographical origin of the buried crops and their social implications. In total, 253,647 crops and 12,071 weeds were identified. Foxtail millet and broomcorn millet represent 61.99 and 30.83% of the total plant remains, with the rest being barley, buckwheat, beans, and hemp. The oxygen isotope and trace elements of the crop and weed remains suggest that broomcorn millet, foxtail millet, barley, buckwheat, and hemp were sourced from different regions. The assemblage of plant remains in the Chashancun cemetery suggests that millet cultivation played an important role in the livelihoods of Tuyuhun descendants, and the location of the elite Tuyuhun cemetery and multisources of different buried crops may reflect their memory of ancestors and homelands. This case study provides a unique perspective to understand the interactions among human subsistence strategy, geopolitical patterns, and local natural environments in northwest China during the late 7th century.

Gut symbiotic bacteria are involved in nitrogen recycling in the tephritid fruit fly Bactrocera dorsalis.

BACKGROUND: Nitrogen is considered the most limiting nutrient element for herbivorous insects. To alleviate nitrogen limitation, insects have evolved various symbiotically mediated strategies that enable them to colonize nitrogen-poor habitats or exploit nitrogen-poor diets. In frugivorous tephritid larvae developing in fruit pulp under nitrogen stress, it remains largely unknown how nitrogen is obtained and larval development is completed. RESULTS: In this study, we used metagenomics and metatranscriptomics sequencing technologies as well as in vitro verification tests to uncover the mechanism underlying the nitrogen exploitation in the larvae of Bactrocera dorsalis. Our results showed that nitrogenous waste recycling (NWR) could be successfully driven by symbiotic bacteria, including Enterobacterales, Lactobacillales, Orbales, Pseudomonadales, Flavobacteriales, and Bacteroidales. In this process, urea hydrolysis in the larval gut was mainly mediated by Morganella morganii and Klebsiella oxytoca. In addition, core bacteria mediated essential amino acid (arginine excluded) biosynthesis by ammonium assimilation and transamination. CONCLUSIONS: Symbiotic bacteria contribute to nitrogen transformation in the larvae of B. dorsalis in fruit pulp. Our findings suggest that the pattern of NWR is more likely to be applied by B. dorsalis, and M. morganii, K. oxytoca, and other urease-positive strains play vital roles in hydrolysing nitrogenous waste and providing metabolizable nitrogen for B. dorsalis.

Shift in subsistence crop dominance from broomcorn millet to foxtail millet around 5500 BP in the western Loess Plateau.

Broomcorn and foxtail millet were the most important crops in northern China during the Neolithic period. Although the significance of broomcorn millet in human subsistence exceeded that of foxtail millet during the early Neolithic, this pattern was reversed by the end of Neolithic period. However, the process underlying this shift remains unclear. The recent excavation of the Gedachuan (GDC) in Zhangjiachuan county has revealed an abundance of relics including millet crop remains from relatively continuous strata of the Yangshao and Qijia cultures, and therefore provides a unique opportunity to examine how and when foxtail millet replaced broomcorn millet as the dominant crop in the western Loess Plateau during the Neolithic period. In this study, we identify 1,738 and 2,686 broomcorn and foxtail millet remains, respectively, from 74 flotation samples, accounting for 38.81% and 59.98% of total plant remains, respectively. Compared with 23 direct dates of carbonized crop grains in GDC, we propose that the weight of foxtail millet in plant subsistence of GDC first exceeded that of broomcorn millet as early as ∼5,500 BP, filling an important gap in the archaeobotanical record from the western Loess Plateau. Further comparative analysis of multidisciplinary data suggests the shift in significance of these two millet crops during the late Neolithic may have been triggered by variations in human settlement intensity and climate change in the western Loess Plateau. The results of this study also suggest that the Banpo Phase of Yangshao Culture survived in the western Loess Plateau as late as ∼5,600 BP.

Sex-Biased Population Admixture Mediated Subsistence Strategy Transition of Heishuiguo People in Han Dynasty Hexi Corridor.

The Hexi Corridor was an important arena for culture exchange and human migration between ancient China and Central and Western Asia. During the Han Dynasty (202 BCE-220 CE), subsistence strategy along the corridor shifted from pastoralism to a mixed pastoralist-agriculturalist economy. Yet the drivers of this transition remain poorly understood. In this study, we analyze the Y-chromosome and mtDNA of 31 Han Dynasty individuals from the Heishuiguo site, located in the center of the Hexi Corridor. A high-resolution analysis of 485 Y-SNPs and mitogenomes was performed, with the Heishuiguo population classified into Early Han and Late Han groups. It is revealed that (1) when dissecting genetic lineages, the Yellow River Basin origin haplogroups (i.e., Oα-M117, Oß-F46, Oγ-IMS-JST002611, and O2-P164+, M134-) reached relatively high frequencies for the paternal gene pools, while haplogroups of north East Asian origin (e.g., D4 and D5) dominated on the maternal side; (2) in interpopulation comparison using PCA and Fst heatmap, the Heishuiguo population shifted from Southern-Northern Han cline to Northern-Northwestern Han/Hui cline with time, indicating genetic admixture between Yellow River immigrants and natives. By comparison, in maternal mtDNA views, the Heishuiguo population was closely clustered with certain Mongolic-speaking and Northwestern Han populations and exhibited genetic continuity through the Han Dynasty, which suggests that Heishuiguo females originated from local or neighboring regions. Therefore, a sex-biased admixture pattern is observed in the Heishuiguo population. Additionally, genetic contour maps also reveal the same male-dominated migration from the East to Hexi Corridor during the Han Dynasty. This is also consistent with historical records, especially excavated bamboo slips. Combining historical records, archeological findings, stable isotope analysis, and paleoenvironmental studies, our uniparental genetic investigation on the Heishuiguo population reveals how male-dominated migration accompanied with lifestyle adjustments brought by these eastern groups may be the main factor affecting the subsistence strategy transition along the Han Dynasty Hexi Corridor.

PUM1 is upregulated by DNA methylation to suppress antitumor immunity and results in poor prognosis in pancreatic cancer.

BACKGROUND: Pancreatic carcinoma (PAAD) is a highly malignant cancer with a poor prognosis and high mortality rate. Pumilio homologous protein 1 (PUM1) promotes cell growth, invasion, and metastasis and suppresses apoptosis in many different kinds of cancers, such as non-small-cell lung carcinoma (NSCLC), ovarian cancer and lymphocyte leukemia. However, the underlying mechanism and potential role of PUM1 in PAAD have not been investigated. METHODS: Bioinformatics analysis was performed using multiple databases [The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), BBCancer, Human Protein Atlas (HPA), MethSurv, cBioPortal, The Cancer Imaging Archive (TCIA), xCell, Gene Expression Omnibus (GEO)] to explore the diagnostic and prognostic role of PUM1, and the relationship between expression of PUM1 and prognosis of patients with PAAD. The analysis was further validated using the Kaplan-Meier plotter. RESULTS: PUM1 plays a role in both diagnostic and prognostic prediction. The PUM1 mRNA expression level correlates with both the prognosis and incidence of pancreatic cancer. PUM1 can serve as a potential diagnostic indicator for pancreatic cancer. Furthermore, the DNA methylation levels of PUM1 affects its oncogene function in pancreatic cancer. PUM1 can also inhibit the immune microenvironment by altering immune cell infiltration, which affects immunotherapy response in pancreatic cancer. CONCLUSIONS: PUM1 takes a crucial part in the immune microenvironment and immunotherapy response of PAAD and is potentially useful for the development of novel diagnostic and treatment strategies.

Human Positive Coactivator 4 Affects the Progression and Prognosis of Pancreatic Ductal Adenocarcinoma via the mTOR/P70s6k Signaling Pathway.

INTRODUCTION: Pancreatic cancer is one of the deadliest cancers in the world, and pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all cases. Human positive coactivator 4 (PC4) is a transcriptional coactivator that has been associated with the development and progression of several tumors. However, no studies investigated the potential role of PC4 in PDAC. METHODS: We investigated PC4 expression in 81 PDAC tissue samples using immunohistochemistry and studied the impact of PC4 expression and the molecular mechanisms of this altered expression on PDAC tumorigenesis and proliferation both in vitro and in vivo. RESULTS: PC4 overexpression was correlated with a poor outcome in PDAC patients. The RNAi-mediated knockdown of PC4 expression in CFPAC-1 and AsPC-1 cell lines reduced cell proliferation and tumor growth. The loss of PC4 in PDAC inhibits cell growth by inducing cell cycle arrest at the G1/S transition and suppressing the mTOR/p70s6k pathway. DISCUSSION/CONCLUSION: Our findings reveal for the first time that PC4 exerts oncogenic functions by activating mTOR/p70s6k signaling pathway-mediated cell proliferation, implying that PC4 is a promising therapeutic target for PDAC.

PUM1 knockdown prevents tumor progression by activating the PERK/eIF2/ATF4 signaling pathway in pancreatic adenocarcinoma cells.

Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with very poor prognosis. Therefore, it is important to fully understand the molecular mechanism underlying its occurrence and development. Pumilio RNA-binding family member 1 (PUM1) has been reported to function as an oncogene in ovarian cancer and nonsmall cell lung cancer. However, its role and mechanism in PDAC have not been fully illuminated. Here, we found that the PUM1 protein levels were higher in PDAC tissues than in adjacent tissues and that PUM1 levels were significantly associated with TNM stage and overall survival time, indicating a correlation between high PUM1 expression and poor prognosis in patients with PDAC. In vitro and in vivo assays showed that PUM1 knockdown inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), and promoted apoptosis in MIA PaCa-2 and PANC-1 cells. Through cDNA microarrays and ingenuity pathway analysis, we found that the activation of the eIF2 signaling pathway significantly correlated with PUM1 knockdown. These results were further confirmed by the increased levels of key components of the eIF2 signaling pathway, p-PERK, p-EIF2A, and ATF4 in PUM1 knockdown cells. We also found that PUM1 levels have a significant negative correlation with p-PERK levels in PDAC tissues and that PERK overexpression inhibited cell proliferation, migration, invasion, and EMT, and promoted apoptosis in vitro. Moreover, a PERK inhibitor alleviated the effects of PUM1 knockdown on cell proliferation, apoptosis, migration, invasion, and EMT. Taken together, our results revealed that PUM1 knockdown suppressed cell growth, invasion, and metastasis, and promoted apoptosis by activating the PERK/eIF2/ATF4 signaling pathway in PDAC cells. PUM1 could be a potential target to develop pharmaceuticals and novel therapeutic strategies for the treatment of PDAC.