Amyloid A and lactic acid as a predictor in patients with sepsis in patients with liver cirrhosis.

BACKGROUND: Sepsis is triggered by pathogenic microorganisms, resulting in a systemic inflammatory response. Liver cirrhosis and sepsis create a vicious cycle: cirrhosis weakens immune function, raising infection risk and hindering pathogen clearance. Optimal treatment outcomes depend on understanding liver cirrhosis patients' sepsis risk factors. Thus, preventing sepsis involves addressing these risk factors. Therefore, early identification and understanding of clinical characteristics in liver cirrhosis patients with sepsis are crucial for selecting appropriate antibiotics. A case-control study using logistic regression was conducted to examine the prognostic value of amyloid A/lactate level monitoring in identifying sepsis risk factors in liver cirrhosis patients. METHODS: From March 2020 to March 2022, 136 liver cirrhosis patients treated at our hospital were divided into a sepsis group (n = 35) and a non-sepsis group (n = 101) based on sepsis complications. General clinical data were collected. Univariate analysis screened for liver cirrhosis patients' sepsis risk factors. Multivariate logistic analysis was subsequently employed to evaluate the risk factors. Sepsis patients were followed up for a month. Based on prognosis, patients were categorized into a poor prognosis group (n = 16) and a good prognosis group (n = 19). Serum amyloid A (SAA) and blood lactic acid (BLA) levels were compared between the two groups. The receiver operating characteristic (ROC) curve was used to evaluate the prognostic value of both individual and combined SAA/BLA monitoring. RESULTS: Patient data, including age, diabetes history, liver cancer, hepatic artery embolization, recent antibiotic use, invasive procedures within two weeks, APACHE II Scoring, ALB and SAA and BLA levels, were compared between the sepsis and non-sepsis groups, showing significant differences (P < 0.05). Logistic regression identified factors such as age ≥ 70, recent antibiotic use, recent invasive procedures, history of liver cancer, hepatic artery embolization history, high APACHE II scores, decreased albumin, and elevated SAA and BLA levels as independent sepsis risk factors in liver cirrhosis patients (P < 0.05). Among the 35 sepsis patients, 16 had a poor prognosis, representing an incidence rate of 45.71%. Serum SAA and BLA levels were significantly higher in the poor prognosis group than in the good prognosis group (P < 0.05). The AUC for serum SAA and BLA was 0.831 (95%CI: 0.738-0.924), 0.720 (95%CI: 0.600-0.840), and 0.909 (95%CI: 0.847-0.972), respectively. The combined diagnostic AUC was significantly higher than that of single factor predictions (P < 0.05). The predictive value ranked as follows: joint detection > SAA > BLA. CONCLUSION: In treating liver cirrhosis, prioritize patients with advanced age, a history of hepatic artery embolization, recent invasive operations, history of liver cancer, recent antibiotic exposure, high APACHE II scores and low albumin. Closely monitoring serum SAA and BLA levels in these patients can offer valuable insights for early clinical prevention and treatment.

Intracellular Gelation-Mediated Living Bacteria for Advanced Biotherapeutics in Mouse Models.

Despite its significant potential in various disease treatments and diagnostics, microbiotherapy is consistently plagued by multiple limitations ranging from manufacturing challenges to in vivo functionality. Inspired by the strategy involving nonproliferating yet metabolically active microorganisms, we report an intracellular gelation approach that can generate a synthetic polymer network within bacterial cells to solve these challenges. Specifically, poly(ethylene glycol dimethacrylate) (PEGDA, 700 Da) monomers are introduced into the bacterial cytosol through a single cycle of freeze-thawing followed by the initiation of intracellular free radical polymerization by UV light to create a macromolecular PEGDA gel within the bacterial cytosol. The molecular crowding resulting from intracytoplasmic gelation prohibits bacterial division and confers robust resistance to simulated gastrointestinal fluids and bile acids while retaining the ability to secrete functional proteins. Biocompatibility assessments demonstrate that the nondividing gelatinized bacteria are effective in alleviating systemic inflammation triggered by intravenous Escherichia coli injection. Furthermore, the therapeutic efficacy of gelatinized Lactobacillus rhamnosus in colitis mice provides additional support for this approach. Collectively, intracellular gelation indicates a universal strategy to manufacture next-generation live biotherapeutics for advanced microbiotherapy.

A Randomized, Controlled Trial of Continuous Heparin Infusion to Prevent Asymptomatic Catheter-Related Thrombosis at Discharge in Infants After Cardiac Surgery: The CHIP-CRT Trial.

OBJECTIVES: There are conflicting results in preventing catheter-related thrombosis (CRT). Continuing infusion of unfractionated heparin (UFH) was a potential option for CRT. This study was to determine the effect of continuous UFH infusion on asymptomatic CRT at discharge in infants after cardiac surgery. STUDY DESIGN: This study was a randomized, placebo-controlled, clinical trial at a single center. All infants with central venous catheters after cardiac surgery, below 3 months of age, were eligible. Stratified by CRT, infants were randomly assigned to the UFH group or the normal saline group. UFH was initiated at a speed of 10 to 15 units/kg/h for infants with CRT and 2 to 3 units/kg/h without CRT. The primary outcome was to determine the rate of CRT at discharge. The secondary outcomes included thrombosis 6 months after surgery, adverse events of UFH, and post-thrombotic symptoms. RESULTS: Due to slow recruitment during the COVID-19 pandemic, this trial was prematurely stopped. Only 35 infants were randomly assigned to the UFH or control groups. There was no statistically significant difference in CRT rate at discharge (P=0.429) and 6 months after surgery (P=1.000) between groups. All CRTs except one disappeared at discharge. No thrombosis or post-thrombotic symptom was reported at follow-up evaluation. There was no difference between groups in duration of thrombus (P=0.088), D dimer (P=0.412), catheter in situ days (P=0.281), and post-thrombotic syndrome (P=1.000), except for activated partial thromboplastin time (P=0.001). CONCLUSIONS: With the early stop of this trial and limited data, it is difficult to draw a definitive conclusion about the efficacy of UFH on CRT. Meanwhile, considering the data from 6 months follow-up, in this population, asymptomatic CRT might resolve with no intervention.

MdbHLH160 is stabilized via reduced MdBT2-mediated degradation to promote MdSOD1 and MdDREB2A-like expression for apple drought tolerance.

Drought stress is a key environmental factor limiting the productivity, quality, and geographic distribution of crops worldwide. Abscisic acid (ABA) plays an important role in plant drought stress responses, but the molecular mechanisms remain unclear. Here, we report an ABA-responsive bHLH transcription factor, MdbHLH160, which promotes drought tolerance in Arabidopsis (Arabidopsis thaliana) and apple (Malus domestica). Under drought conditions, MdbHLH160 is directly bound to the MdSOD1 (superoxide dismutase 1) promoter and activated its transcription, thereby triggering reactive oxygen species (ROS) scavenging and enhancing apple drought tolerance. MdbHLH160 also promoted MdSOD1 enzyme activity and accumulation in the nucleus through direct protein interactions, thus inhibiting excessive nuclear ROS levels. Moreover, MdbHLH160 directly upregulated the expression of MdDREB2A-like, a DREB (dehydration-responsive element binding factor) family gene that promotes apple drought tolerance. Protein degradation and ubiquitination assays showed that drought and ABA treatment stabilized MdbHLH160. The BTB protein MdBT2 was identified as an MdbHLH160-interacting protein that promoted MdbHLH160 ubiquitination and degradation, and ABA treatment substantially inhibited this process. Overall, our findings provide insights into the molecular mechanisms of ABA-modulated drought tolerance at both the transcriptional and post-translational levels via the ABA-MdBT2-MdbHLH160-MdSOD1/MdDREB2A-like cascade.

A novel approach for exploring the regional features of vaginal fluids based on microbial relative abundance and alpha diversity.

Vaginal fluids are one of the most common biological samples in forensic sexual assault cases, and their characterization is vital to narrow the scope of investigation. Presently, approaches for identifying vaginal fluids in different regions are not only rare but also have certain limitations. However, the microbiome has shown the potential to identify the source of body fluids and reveal the characteristics of individuals. In this study, 16S rRNA gene high-throughput sequencing was used to characterize the vaginal microbial community from three regions, Sichuan, Hainan and Hunan. In addition, data on relative abundance and alpha diversity were used to construct a random forest model. The results revealed that the dominant genera in the three regions were Lactobacillus, followed by Gardnerella. In addition, Ureaplasma, Nitrospira, Nocardiodes, Veillonella and g-norank-f-Vicinamibacteraceae were significantly enriched genera in Sichuan, llumatobacter was enriched in Hainan, and Pseudomonas was enriched in Hunan. The random forest classifier based on combined data on relative abundance and alpha diversity had a good ability to distinguish vaginal fluids with similar dominant microbial compositions in the three regions. The study suggests that combining high-throughput sequencing data with machine learning models has good potential for application in the biogeographic inference of vaginal fluids.

MdHB7-like positively modulates apple salt tolerance by promoting autophagic activity and Na+ efflux.

Salt stress adversely affects the yield and quality of crops and limits their geographical distribution. Studying the functions and regulatory mechanisms of key genes in the salt stress response is important for breeding crops with enhanced stress resistance. Autophagy plays an important role in modulating the tolerance of plants to various types of abiotic stressors. However, the mechanisms underlying salt-induced autophagy are largely unknown. Cation/Ca2+ exchanger proteins enhance apple salt tolerance by inhibiting Na+ accumulation but the mechanism underlying the response to salt stress remains unclear. Here, we show that the autophagy-related gene MdATG18a modulated apple salt tolerance. Under salt stress, the autophagic activity, proline content, and antioxidant enzyme activities were higher and Na+ accumulation was lower in MdATG18a-overexpressing transgenic plants than in control plants. The use of an autophagy inhibitor during the salt treatment demonstrated that the regulatory function of MdATG18a depended on autophagy. The yeast-one-hybrid assay revealed that the homeodomain-leucine zipper (HD-Zip) transcription factor MdHB7-like directly bound to the MdATG18a promoter. Transcriptional regulation and genetic analyses showed that MdHB7-like enhanced salt-induced autophagic activity by promoting MdATG18a expression. The analysis of Na+ efflux rate in transgenic yeast indicated that MdCCX1 expression significantly promoted Na+ efflux. Promoter binding, transcriptional regulation, and genetic analyses showed that MdHB7-like promoted Na+ efflux and apple salt tolerance by directly promoting MdCCX1 expression, which was independent of the autophagy pathway. Overall, our findings provide insight into the mechanism underlying MdHB7-like-mediated salt tolerance in apple through the MdHB7-like-MdATG18a and MdHB7-like-MdCCX1 modules. These results will aid future studies on the mechanisms underlying stress-induced autophagy and the regulation of stress tolerance in plants.

Acteoside improves adipocyte browning by CDK6-mediated mTORC1-TFEB pathway.

Adipocyte browning increases energy expenditure by thermogenesis, which has been considered a potential strategy against obesity and its related metabolic diseases. Phytochemicals derived from natural products with the ability to improve adipocyte thermogenesis have aroused extensive attention. Acteoside (Act), a phenylethanoid glycoside, exists in various medicinal or edible plants and has been shown to regulate metabolic disorders. Here, the browning effect of Act was evaluated by stimulating beige cell differentiation from the stromal vascular fraction (SVF) in the inguinal white adipose tissue (iWAT) and 3T3-L1 preadipocytes, and by converting the iWAT-SVF derived mature white adipocytes. Act improves adipocyte browning by differentiation of the stem/progenitors into beige cells and by direct conversion of mature white adipocytes into beige cells. Mechanistically, Act inhibited CDK6 and mTOR, and consequently relieved phosphorylation of the transcription factor EB (TFEB) and increased its nuclear retention, leading to induction of PGC-1α, a driver of mitochondrial biogenesis, and UCP1-dependent browning. These data thus unveil a CDK6-mTORC1-TFEB pathway that regulates Act-induced adipocyte browning.

Self-Assembled Copper-Based Nanoparticles for Glutathione Activated and Enzymatic Cascade-Enhanced Ferroptosis and Immunotherapy in Cancer Treatment.

As an emerging cancer treatment strategy, ferroptosis is greatly restricted by excessive glutathione (GSH) in tumor microenvironment (TME) and low reactive oxygen species (ROS) generation efficiency. Here, this work designs self-assembled copper-alanine nanoparticles (CACG) loaded with glucose oxidase (GOx) and cinnamaldehyde (Cin) for in situ glutathione activated and enzymatic cascade-enhanced ferroptosis and immunotherapy. In response to GSH-rich and acidic TME, CACG allows to effectively co-deliver Cu2+ , Cin, and GOx into tumors. Released Cin consumes GSH through Michael addition, accompanying with the reduction of Cu2+ into Cu+ for further GSH depletion. With the cascade of Cu+ -catalyzed Fenton reactions and enzyme-catalyzed reactions by GOx, CACG could get rid of the restriction of insufficient hydrogen peroxide in TME, leading to a robust and constant generation of ROS. With the high efficiency of GSH depletion and ROS production, ferroptosis is significantly enhanced by CACG in vivo. Moreover, elevated oxidative stress triggers robust immune responses by promoting dendritic cells maturation and T cell infiltration. The in vivo results prove that CACG could efficiently inhibit tumor growth in 4T1 tumor-bearing mouse model without causing obvious systemic toxicity, suggesting the great potential of CACG in enhancing ferroptosis and immunotherapy for effective cancer treatment.

Hyperoside prevents high-fat diet-induced obesity by increasing white fat browning and lipophagy via CDK6-TFEB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Hypericum perforatum L. (genus Hypericum, family Hypericaceae) is a flowering plant native to Europe, North Africa and Asia, which can be used in the treatment of psychiatric disorder, cardiothoracic depression and diabetes. Crataegus pinnatifida Bunge (genus Crataegus pinnatifida Bunge, family Rosaceae) was another traditional Chinese medicine for treating hyperlipidemia. Hyperoside (Hype), a major flavonoid glycoside component of Hypericum perforatum L. and Crataegus pinnatifida Bunge, possesses multiple physiological activities, such as anti-inflammatory and antioxidant effects. However, the role of Hype on obesity and related metabolic diseases still needs to be further investigated. AIM OF THE STUDY: We explored the effect of Hype on high-fat diet (HFD)-induced obesity and its metabolic regulation on white fat tissues. MATERIALS AND METHODS: In vivo four-week-old male C57BL/6J mice were randomly assigned to vehicle (0.5% methycellulose) and Hype (80 mg/kg/day by gavage) group under a normal chow diet (NCD) or HFD for 8 weeks. In vitro, 3T3-L1 preadipocyte cell line and primary stromal vascular fraction (SVF) cells from inguinal white adipose tissue (iWAT) of mice were used to investigate the molecular mechanisms of Hype regulation on adipocyte energy metabolism. RESULTS: Hype treatment in vivo promotes UCP1-dependent white to beige fat transition, increases glucose and lipid metabolism, and resists HFD-induced obesity. Meanwhile, Hype induces lipophagy, a specific autophagy that facilitates the breakdown of lipid droplets, and blocking autophagy partially reduces UCP1 expression. Mechanistically, Hype inhibited CDK6, leading to the increased nuclear translocation of TFEB, while overexpression of CDK6 partially reversed the enhancement of UCP1 by Hype. CONCLUSIONS: Hype protects mice from HFD-induced obesity by increasing energy expenditure of white fat tissue via CDK6-TFEB pathway.

Colon-targeted bacterial hydrogel for tumor vascular normalization and improved chemotherapy.

The endogenous H2S plays an important role in the occurrence and development of colon cancer, and is related to the abnormal blood vessels. Here, we reported on a sulfhydryl hyaluronid-based hydrogel (HA-SH) synthesized by amide reaction and further obtained a bacterial hydrogel by loading Thiobacillus denitrificans to the hydrogel for targeting adhesion to the colon. It was found that the loaded bacteria in HA-SH hydrogel can scavenge excess H2S in colon cancer, then promote tumor vascular normalization and improve the delivery of chemotherapy drug CPT to inhibit tumor progression. Both in vivo and in vitro experiments show that the self-crosslinked bacterial hydrogel has satisfactory effects in inhibiting tumor progression and promoting tumor vascular normalization in colon cancer. This study presents an efficient method to target the colon and consume overexpressed H2S in colon cancer to inhabit tumor progression, providing a new way for oral drug treatment of colon cancer.

Precise A∙T to G∙C base editing in the allotetraploid rapeseed (Brassica napus L.) genome.

Rapeseed is an important source of oilseed crop in the world. Achieving genetic improvement has always been the major goal in rapeseed production. Single nucleotide substitution is the basis of most genetic variation underpinning important agronomic traits. Nowadays, Cas-base editing acts as an efficient tool to mediate single-base substitution at the target site. In this study, four adenine base editors (ABE) were modified to achieve adenosine base editing at different genome sites in allotetraploid Brassica napus. We designed 18 small guide RNAs to target phytoene desaturase (PDS), acetolactate synthase (ALS), CLAVATA3 (CLV3), CLV2, TRANSPARENT TESTA12 (TT12), carotenoid isomerase (CRTISO), designated de-etiolated-2 (DET2), BRANCHED1 (BRC1), zeaxanthin epoxidase (ZEP) genes, respectively. Among the four ABE systems, pBGE17 had the highest base-editing efficiency, with an average editing efficiency of 3.51%. Target sequencing results revealed that the editing window ranged from A5 to A8 of the protospacer-adjacent motif (PAM) sequence. Moreover, the ABEmax-nCas9NG system with NG PAM was developed, with a base-editing efficiency of 1.22%. These results revealed that ABE system developed in this study could efficiently induce A to G substitution and the ABE-nCas9NG system could broaden editing window in oilseed rape.

A heterogenic membrane-based biomimetic hybrid nanoplatform for combining radiotherapy and immunotherapy against breast cancer.

Radiotherapy is adopted to obliterate multiple malignant tumors clinically, which might also induce antitumor immune response. However, traditional radiotherapy is not enough to ablate tumors and activate long-term immunological response. Here, we developed a hybrid nanoplatform (MGTe) composed of GTe (glutathione (GSH) decorated Te nanoparticles) and fusing tumor cell membranes (TM) and bacterial outer membranes (BM). In this nanoplatform, GTe was designed for radiotherapy sensitization, concurrently the fusion of TM and BM was expected for amplifying antitumor immune. With a high-Z element, MGTe could enhance radiosensitivity by reactive oxygen species (ROS) production and cancer cell immunogenic death (ICD) under X-ray irradiation, which would also trigger antitumor immune. At meanwhile, TM and BM would further enlarge the immunological effects through antigen presenting cells (APCs) maturation and cytotoxic T lymphocytes (CTLs) stimulation. In this synergistic strategy, the combination of MGTe and X-ray showed significant tumor inhibition by radiation-driven immunotherapy, which will find great potential as an attractive clinical alternative to fight against tumor with reduced side effects.

Discovery of Novel Variants on the CHD7 Gene: A Case Series of CHARGE Syndrome.

Background: CHARGE syndrome (CS) is a single-gene genetic disorder with multiple organ malformations caused by a variant of the chromodomain helicase DNA-binding protein 7 (CHD7) gene on chromosome 8q12.1. In this study, we aimed to investigate new variants that have emerged in these cases compared with typical CS and the relationship between the genes and phenotypes. Methods: Patients with suspected genetic diseases were subjected to Whole Exome Sequencing (WES) at a genetics laboratory in Guangzhou. The average sequencing coverage depth was >200 ×, and 96% was >20 ×. The variant interpretation was manipulated according to the American College of Medical Genetics (ACMG) guidelines. Molecular data on databases for ClinVar and CHD7 were also collected and collated. We reviewed the currently described CHD7 variants and analyzed the genetic variation and phenotypic heterogeneity. Results: Data of 12 patients with CS from four hospitals in China were collected. According to gestational age, most of them (8/12) were near-term babies with a lower birth weight than their peers, averaging 2.62 kg. In this study, the most common phenotypes were respiratory tract malformations (11/12), heart malformations (10/12), and central nervous system malformations (9/12). Two fetuses were confirmed to have brain or heart abnormalities during prenatal testing, while 10/12 were found to have abnormalities during prenatal testing. The maximum Acute Physiology and Chronic Health Evaluation (APACHE II) score at admission was 19, and the average was 11.58. Five variants in the CHD7 gene c.7012C > T (p.Q2338*), c.7868delC (p.P2623Rfs*16), c.5405-3C > G, c.6936 + 2T > C, and c.8077-2A > G) were novel and were located in exons 33, 36, and introns 25, 32, and 37, respectively. There may be a positive correlation between exon location and phenotype. Conclusion: Five novel variants were discovered. These expanded the mutational spectrum of the CHD7 gene and the phenotype of CS. There may be a correlation between the new mutation sites and the phenotype, which has some reference value for the evaluation of mutation sites.

Double Bacteria Synergistic Catalytic Reduction System for Heavy Metal Detoxification Treatment.

Synthetic biology has promoted the development of microbial therapy, but the scope of applicable microbial species is limited and transgenic microorganisms also display safety risks for in vivo applications. Interestingly, symbiotic microorganisms in nature can achieve functional updates by metabolic cooperation. Here, we report on a nongenetic method for engineering microorganisms to construct a heavy metal ion reduction system, which was prepared by linking Shewanella oneidensis MR-1 (SO) and Lactobacillus rhamnosus GG (LGG). SO could reduce metal ions but is limited by finite substrates in vivo. LGG could metabolize glucose to lactate as a substrate for SO, promoting extracellular electron transfer by SO and heavy metal ion reduction. Meanwhile, SO could generate electron donor cytochrome C to promote metabolism of LGG, forming metabolic synergy and circulation between these two bacteria. The SO-LGG system shows splendid ability to remove heavy metal ions and inflammatory modulation in acute or chronic heavy metal poisoning.

Fine mapping and analysis of candidate genes for qFT7.1, a major quantitative trait locus controlling flowering time in Brassica rapa L.

KEY MESSAGE: qFT7.1, a major QTL for flowering time in Brassica rapa was fine-mapped to chromosome A07 in a 56.4-kb interval, in which the most likely candidate gene is BraA07g018240.3C. In Brassica rapa, flowering time (FT) is an important agronomic trait that affects the yield, quality, and adaption. FT is a complicated trait that is regulated by many genes and is affected greatly by the environment. In this study, a chromosome segment substitution line (CSSL), CSSL16, was selected that showed later flowering than the recurrent parent, a rapid-cycling inbred line of B. rapa (RcBr). Using Bulked Segregant RNA sequencing, we identified a late flowering quantitative trait locus (QTL), designated as qFT7.1, on chromosome A07, based on a secondary-F2 population derived from the cross between CSSL16 and RcBr. qFT7.1 was further validated by conventional QTL mapping. This QTL explained 39.9% (logarithm of odds = 32.2) of the phenotypic variations and was fine mapped to a 56.4-kb interval using recombinant analysis. Expression analysis suggested that BraA07g018240.3C, which is homologous to ATC (encoding Arabidopsis thaliana CENTRORADIALIS homologue), a gene for delayed flowering in Arabidopsis, as the most promising candidate gene. Sequence analysis demonstrated that two synonymous mutations existed in the coding region and numerous bases replacements existed in promoter region between BraA07g018240.3C from CSSL16 and RcBr. The results will increase our knowledge related to the molecular mechanism of late flowering in B. rapa and lays a solid foundation for the breeding of late bolting B. rapa.

Research progress in AIE-based crystalline porous materials for biomedical applications.

Crystalline porous materials (CPMs) not only present the precise integration of molecular building blocks into extensible structures with periodic frameworks and regular pores, but also provide limited molecular spaces for the interactions of guest molecules, electrons and photons. Incorporating aggregation-induced emission (AIE)-based units into crystalline porous frameworks can result in unique luminescent properties. AIE-based CPMs have widely tunable composition, high luminescent efficiency and good photo-stability, which make them useful for biomedical applications involving bio-sensing, bio-imaging and imaging-guided therapies. This review focused on structure design and luminescent property modulation of AIE-based CPMs with highlights on their applications in biomedical fields. The prospect and challenges in the development of AIE-based CPMs from chemistry, materials to biomedical applications were also discussed.

Diosgenin Ameliorates Non-alcoholic Fatty Liver Disease by Modulating the Gut Microbiota and Related Lipid/Amino Acid Metabolism in High Fat Diet-Fed Rats.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disease closely associated with dietary habits. Diosgenin is abundant in yam, a common food and traditional Chinese medicine. The molecular mechanism of diosgenin on NAFLD has been preliminarily explored. However, the effect of diosgenin on metabolism and gut microbiota in NAFLD has not been reported. This study confirmed that diosgenin could suppress excessive weight gain, reduce serum levels of total cholesterol and triglycerides, and decrease liver fat accumulation in high-fat diet-induced NAFLD rats. Moreover, fecal metabolomics analysis suggested diosgenin improved abnormal lipid and amino acid metabolism. Bile acids, including lithocholic acid and ursodeoxycholic acid 3-sulfate that function as excretion, absorption, and transport of fats, were remarkably regulated by diosgenin. Aromatic amino acid and lysine metabolism was regulated by diosgenin as well. 16S rRNA gene sequencing analysis demonstrated that diosgenin restored gut microbiota disorder, especially Globicatella, Phascolarctobacterium, Pseudochrobactrum, and uncultured_bacterium_f_Prevotellaceae at the genus level. Additionally, these regulated bacterial genera showed significant correlations with lipid and amino acid metabolism-related biomarkers. This study further confirmed the significant effect of diosgenin on NAFLD, and provided a new perspective for the mechanism.

Effect of strip clear-cutting on the natural regeneration of Pinus tabuliformis plantations in northeastern China.

In this study, the effect of strip clear-cutting on the natural regeneration performance of mature Pinus tabuliformis plantations in the three locations in western part of the Liaoning Province was analyzed. Strip clear-cutting, with clear-cut and uncut strip widths of 15, 20, 25 m, and 10 and 18 m, respectively, was conducted in spring 2014, and control, in each study location. Field investigations were conducted in 2017. Fifteen sample plots with sizes of 4 m2 (2 m × 2 m) were established in each clear-cut strip, uncut strip, and control. One to four saplings were randomly selected to measure the current year increment, and the lengths and numbers for branch of the first whorl. Three saplings were randomly selected from the center of the strip to measure the photosynthetic rate. Three sample plots with sizes of 4 m2 (2 m × 2 m) and 1 m2 (1 m × 1 m) were developed in each strip and control to determine the biodiversity of shrubs and herbs as well as the water content of the decomposition and semi-decomposition layer. The results show that the current year increment and branch length of the first whorl can be ordered as follows: clear-cut strips > control > uncut strips. Number of the branches of the first whorl can be ordered as follows: clear-cut strips > uncut strips > control. Strip clear-cutting was a statistically significant treatment for the current year increment and length and number of branches of the first whorl. The saplings from the clear-cut strip with a width of 25 m have the largest photosynthetic capacity compared with those from the other strips and control. The transpiration rates of the large, medium, and small saplings from clear-cut strips are the largest and those of saplings from the control are the smallest. The water content of the decomposition and semi-decomposition layer in the control is the highest, but no significant difference was confirmed between the strip clear-cutting approaches.

Progress of engineered bacteria for tumor therapy.

Recently, with the rapid development of bioengineering technology and nanotechnology, natural bacteria were modified to change their physiological activities and therapeutic functions for improved therapeutic efficiency of diseases. These engineered bacteria were equipped to achieve directed genetic reprogramming, selective functional reorganization and precise spatio-temporal control. In this review, research progress in the basic modification methodologies of engineered bacteria were summarized, and representative researches about their therapeutic performances for tumor treatment were illustrated. Moreover, the strategies for the construction of engineered colonies based on engineering of individual bacteria were summarized, providing innovative ideas for complex functions and efficient anti-tumor treatment. Finally, current limitation and challenges of tumor therapy utilizing engineered bacteria were discussed.

CDK6 increases glycolysis and suppresses autophagy by mTORC1-HK2 pathway activation in cervical cancer cells.

Cervical carcinoma is a leading malignant tumor among women worldwide, characterized by the dysregulation of cell cycle. Cyclin-dependent kinase 6 (CDK6) plays important roles in the cell cycle progression, cell differentiation, and tumorigenesis. However, the role of CDK6 in cervical cancer remains controversial. Here, we found that loss of CDK6 in cervical adenocarcinoma HeLa cell line inhibited cell proliferation but induced apoptosis as well as autophagy, accompanied by attenuated expression of mammalian target of rapamycin complex 1 (mTORC1) and hexokinase 2 (HK2), reduced glycolysis, and production of protein, nucleotide, and lipid. Similarly, we showed that CDK6 knockout inhibited the survival of CDK6-high CaSki but not CDK6-low SiHa cervical cancer cells by regulation of glycolysis and autophagy process. Collectively, our studies indicate that CDK6 is a critical regulator of human cervical cancer cells, especially with high CDK6 level, through its ability to regulate cellular apoptosis and metabolism. Thus, inhibition of CDK6 kinase activity could be a powerful therapeutic avenue used to treat cervical cancers.