Establishment and validation of circulating cell-free DNA signatures for nasopharyngeal carcinoma detection.

BACKGROUND: Early detection of nasopharyngeal carcinoma (NPC) poses a significant challenge. The absence of highly sensitive and specific diagnostic biomarkers for nasopharyngeal carcinoma contributes to the unfavourable prognosis of NPC patients. Here, we aimed to establish a non-invasive approach for detecting NPC using circulating cell-free DNA (cfDNA). METHODS: We investigated the potential of next-generation sequencing (NGS) of peripheral blood cells as a diagnostic tool for NPC. We collected data on genome-wide nucleosome footprint (NF), 5'-end motifs, fragmentation patterns, CNV information, and EBV content from 553 Chinese subjects, including 234 NPC patients and 319 healthy individuals. Through case-control analysis, we developed a diagnostic model for NPC, and validated its detection capability. FINDINGS: Our findings revealed that the frequencies of NF, fragmentation, and motifs were significantly higher in NPC patients compared to healthy controls. We developed an NPC score based on these parameters that accurately distinguished NPC from non-NPC cases according to the American Joint Committee on Cancer staging system from non-NPC (validation set: area under curve (AUC) = 99.9% (95% CI: 99.8%-100%), se: 98.15%, sp: 100%). This model showed superior performance over plasma EBV DNA. Additionally, the NPC score effectively differentiated between NPC patients and healthy controls, even after clinical treatment. Furthermore, the NPC score was found to be independent of potential confounders such as age, sex, or TNM stage. INTERPRETATION: We have developed and verified a non-invasive approach with substantial potential for clinical application in detecting NPC. FUNDING: A full list of funding bodies that contributed to this study can be found in Funding section.

Quantitative expression of LNAPL pollutant concentrations in capillary zone by coupling multiple environmental factors based on random forest algorithm.

The capillary zone plays a crucial role in migration and transformation of pollutants. Light nonaqueous liquids (LNAPLs) have become the main organic pollutant in soil and groundwater environments. However, few studies have focused on the concentration distribution characteristics and quantitative expression of LNAPL pollutants within capillary zone. In this study, we conducted a sandbox-migration experiment using diesel oil as a typical LNAPL pollutant, with the capillary zone of silty sand as the research object. The variation characteristics of LNAPL pollutants (total petroleum hydrocarbon) concentration and environmental factors (moisture content, electrical conductivity, pH, and oxidationreduction potential) were essentially consistent at different locations with the same height. These characteristics differed within range of 10.0-50.0 cm and above 60.0 cm from groundwater. A model for quantitative expression of concentrations was constructed by coupling multiple environmental factors of 968 sets-7744 data via random forest algorithm. The goodness of fit (R2) for both training and test sets was greater than 0.90, and the mean absolute percentage error (MAPE) was less than 16.00 %. The absolute values of relative errors in predicting concentrations at characteristic points were less than 15.00 %. The constructed model can accurately and quantitatively express and predict concentrations in capillary zone.

Simulated Gastrointestinal Digestion and Fecal Fermentation Characteristics of Exopolysaccharides Synthesized by Schleiferilactobacillus harbinensis Z171.

Exopolysaccharides (EPSs) produced by Lactobacillus have important physiological activities and are commonly used as novel prebiotics. A strain of Lactobacillus with high EPS yield was identified as Schleiferilactobacillus harbinensis (S. harbinensis Z171), which was isolated from Chinese sauerkraut. The objective of this study was to investigate the in vitro simulated digestion and fecal fermentation behavior of the purified exopolysaccharide fraction F-EPS1A from S. harbinensis Z171 and its influence on the human intestinal flora composition. The in vitro digestion results showed that the primary structural characteristics of F-EPS1A, such as morphology, molecular weight, and monosaccharide composition remained stable after saliva and gastrointestinal digestion. Compared with the blank group, the fermentation of F-SPS1A by fecal microbiota decreased the diversity of the bacterial communities, significantly promoted the relative abundance of Bifidobacterium and Faecalibacterium, and decreased the relative abundance of Lachnospiraceae_Clostridium, Fusobacterium, and Oscillospira. Reverse transcription polymerase chain reaction (RT-PCR) analysis also showed that the population of Bifidobacterium markedly increased. Furthermore, the total short-chain fatty acid levels increased significantly, especially for butyric acid. Gas chromatography-mass spectrometry (GC-MS) results showed that F-EPS1A could be fermented by the human gut microbiota to synthesize organic acids and derivative metabolites that are beneficial to gut health. Therefore, these findings suggest that F-EPS1A could be exploited as a potential prebiotic.

Comparison of Double-Stranded DNA at the 5' and 3' Ends of the G-Triplex and Its Application in the Detection of Hg(II).

Leveraging the fluorescence enhancement effect of the G-triplex (G3)/thioflavin T (ThT) catalyzed by the adjacent double-stranded DNA positioned at the 5' terminus of the G3, the G3-specific oligonucleotide (G3MB6) was utilized to facilitate the rapid detection of mercury (Hg(II)) through thymine-Hg(II)-thymine (T-Hg(II)-T) interactions. G3MB6 adopted a hairpin structure in which partially complementary strands could be disrupted with the presence of Hg(II). It prompted the formation of double-stranded DNA by T-Hg(II)-T, inducing the unbound single strand of G3MB6 to spontaneously form a parallel G3 structure, producing a solid fluorescence signal by ThT. Conversely, fluorescence was absent without Hg(II), since no double strand and formation of G3 occurred. The fluorescence intensity of G3MB6 exhibited a positive correlation with Hg(II) concentrations from 17.72 to 300 nM (R2 = 0.9954), boasting a notably low quality of limitation (LOQ) of 17.72 nM. Additionally, it demonstrated remarkable selectivity for detecting Hg(II). Upon application to detect Hg(II) in milk samples, the recovery rates went from 100.3% to 103.2%.

Plasma ofCS-modified CD44 predicts the survival of patients with lung cancer.

Plasma levels of oncofetal chondroitin sulfate (ofCS)-modified CD44 have emerged as a promising biomarker for multi-cancer detection. Here, we explored its potential to predict the survival of patients with lung cancer. A prospective observational cohort was conducted involving 274 newly diagnosed patients with lung cancer at the Sun Yat-sen University Cancer Center from 2013 to 2015. The plasma levels of ofCS-modified CD44 were measured, and Cox regression analysis was performed to assess the association between plasma-modified CD44 levels and overall survival (OS) as well as other prognostic outcomes. Prognostic nomograms were constructed based on plasma ofCS-modified CD44 levels to predict survival outcomes for patients with lung cancer. Patients with high expression ofCS-modified CD44 exhibited significantly worse outcomes in terms of OS (HR = 1.61, 95%CI = 1.13-2.29, p = 0.009) and progression-free survival (PFS). These findings were consistent across various analyses. The concordance index of the prognostic nomogram for predicting OS in both the training set and validation set were 0.723 and 0.737, respectively. Additionally, time-dependent receiver operating characteristic (ROC) curves showed that the nomogram could serve as a useful tool for predicting OS in patients with lung cancer. Plasma ofCS-modified CD44 may serve as an independent prognosis marker for patients with lung cancer. Further validation of its predictive value could enhance prognostic assessment and guide personalized treatment strategies for patients with lung cancer.

Naringenin relieves paclitaxel-induced pain by suppressing calcitonin gene-related peptide signalling and enhances the anti-tumour action of paclitaxel.

BACKGROUND AND PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) commonly causes neuropathic pain, but its pathogenesis remains unclear, and effective therapies are lacking. Naringenin, a natural dihydroflavonoid compound, has anti-inflammatory, anti-nociceptive and anti-tumour activities. However, the effects of naringenin on chemotherapy-induced pain and chemotherapy effectiveness remain unexplored. EXPERIMENTAL APPROACH: Female and male mouse models of chemotherapy-induced pain were established using paclitaxel. Effects of naringenin were assessed on pain induced by paclitaxel or calcitonin gene-related peptide (CGRP) and on CGRP expression in dorsal root ganglia (DRG) and spinal cord tissue. Additionally, we examined peripheral macrophage infiltration, glial activation, c-fos expression, DRG neuron excitability, microglial M1/M2 polarization, and phosphorylation of spinal NF-κB. Furthermore, we investigated the synergic effect and related mechanisms of naringenin and paclitaxel on cell survival of cancer cells in vitro. KEY RESULTS: Systemic administration of naringenin attenuated paclitaxel-induced pain in both sexes. Naringenin reduced paclitaxel-enhanced CGRP expression in DRGs and the spinal cord, and alleviated CGRP-induced pain in naïve mice of both sexes. Naringenin mitigated macrophage infiltration and reversed paclitaxel-elevated c-fos expression and DRG neuron excitability. Naringenin decreased spinal glial activation and NF-κB phosphorylation in both sexes but influenced microglial M1/M2 polarization only in females. Co-administration of naringenin with paclitaxel enhanced paclitaxel's anti-tumour effect, impeded by an apoptosis inhibitor. CONCLUSION AND IMPLICATIONS: Naringenin's anti-nociceptive mechanism involves CGRP signalling and neuroimmunoregulation. Furthermore, naringenin facilitates paclitaxel's anti-tumour action, possibly involving apoptosis. This study demonstrates naringenin's potential as a supplementary treatment in cancer therapy by mitigating side effects and potentiating efficacy of chemotherapy.

Understanding and exploring the diversity of soil microorganisms in tea (Camellia sinensis) gardens: toward sustainable tea production.

Leaves of Camellia sinensis plants are used to produce tea, one of the most consumed beverages worldwide, containing a wide variety of bioactive compounds that help to promote human health. Tea cultivation is economically important, and its sustainable production can have significant consequences in providing agricultural opportunities and lowering extreme poverty. Soil parameters are well known to affect the quality of the resultant leaves and consequently, the understanding of the diversity and functions of soil microorganisms in tea gardens will provide insight to harnessing soil microbial communities to improve tea yield and quality. Current analyses indicate that tea garden soils possess a rich composition of diverse microorganisms (bacteria and fungi) of which the bacterial Proteobacteria, Actinobacteria, Acidobacteria, Firmicutes and Chloroflexi and fungal Ascomycota, Basidiomycota, Glomeromycota are the prominent groups. When optimized, these microbes' function in keeping garden soil ecosystems balanced by acting on nutrient cycling processes, biofertilizers, biocontrol of pests and pathogens, and bioremediation of persistent organic chemicals. Here, we summarize research on the activities of (tea garden) soil microorganisms as biofertilizers, biological control agents and as bioremediators to improve soil health and consequently, tea yield and quality, focusing mainly on bacterial and fungal members. Recent advances in molecular techniques that characterize the diverse microorganisms in tea gardens are examined. In terms of viruses there is a paucity of information regarding any beneficial functions of soil viruses in tea gardens, although in some instances insect pathogenic viruses have been used to control tea pests. The potential of soil microorganisms is reported here, as well as recent techniques used to study microbial diversity and their genetic manipulation, aimed at improving the yield and quality of tea plants for sustainable production.

Development of a fluorescent DNA sensor for dual detection of heavy metal ions utilising DAPI in distinct buffers.

The DNA-based biosensor utilises a thymine/guanine(T/G)-rich ODN-4 scaffold with 4',6-diamidino-2-phenylindole(DAPI) as a fluorescent emissary to monitor mercury/lead(Hg(II)/Pb(II)) ions simultaneously. Key to its bifocal detection capability is the twin unbound cytosine(C) bases strategically bridging the G-quadruplex and T-rich sequences, enabling their synergistic interplay. It facilitates the recognition of Hg(II)/Pb(II) ions, characterised by high specificity, and effectively mitigates interference from silver(Ag(I)). The G-quadruplex, guided by the C bases, induces a conformational transition in T-Hg(II)-T complexes, resulting in intense fluorescence. Pb(II) causes a spatial shift in the G-quadruplex, relaxing the T-Hg(II)-T base pairs and attenuating the fluorescence signal. The ODN-4 exhibits a robust, linear correlation with Hg(II) concentration (4.09 nmol/L to 1000 nmol/L) and Pb(II) concentration (3.22 nmol/L to 5 µmol/L). Recovery rates in milk, tap water, and rice water specimens with both ions validate method accuracy (Hg(II): 95.19% to 104.68%, Pb(II): 98.20% to 103.46%). It holds promising prospects for practical food analysis.

Germacrone alleviates breast cancer-associated osteolysis by inhibiting osteoclastogenesis via inhibition of MAPK/NF-κB signaling pathways.

Bone is one of the most frequent sites for metastasis in breast cancer patients. Bone metastasis significantly reduces the survival time and the life quality of breast cancer patients. Germacrone (GM) can serve humans as an anti-cancer and anti-inflammation agent, but its effect on breast cancer-induced osteolysis remains unclear. This study aims to investigate the functions and mechanisms of GM in alleviating breast cancer-induced osteolysis. The effects of GM on osteoclast differentiation, bone resorption, F-actin ring formation, and gene expression were examined in vitro. RNA-sequencing and Western Blot were conducted to explore the regulatory mechanisms of GM on osteoclastogenesis. The effects of GM on breast cancer-induced osteoclastogenesis, and breast cancer cell malignant behaviors were also evaluated. The in vivo efficacy of GM in the ovariectomy model and breast cancer bone metastasis model with micro-CT and histomorphometry. GM inhibited osteoclastogenesis, bone resorption and F-actin ring formation in vitro. Meanwhile, GM inhibited the expression of osteoclast-related genes. RNA-seq analysis and Western Blot confirmed that GM inhibited osteoclastogenesis via inhibition of MAPK/NF-κB signaling pathways. The in vivo mouse osteoporosis model further confirmed that GM inhibited osteolysis. In addition, GM suppressed the capability of proliferation, migration, and invasion and promoted the apoptosis of MDA-MB-231 cells. Furthermore, GM could inhibit MDA-MB-231 cell-induced osteoclastogenesis in vitro and alleviate breast cancer-associated osteolysis in vivo human MDA-MB-231 breast cancer bone metastasis-bearing mouse models. Our findings identify that GM can be a promising therapeutic agent for patients with breast cancer osteolytic bone metastasis.

Feedback regulation of the isoprenoid pathway by SsdTPS overexpression has the potential to enhance plant tolerance to drought stress.

In order to maintain the dynamic physiological balance, plants are compelled to adjust their energy metabolism and signal transduction to cope with the abiotic stresses caused by complex and changeable environments. The diterpenoid natural compound and secondary metabolites, sclareol, derived from Salvia sclarea, has gained significant attention owing to its economic value as a spice material and diverse physiological activities. Here, we focused on the roles and regulatory mechanisms of the sclareol diterpene synthase gene SsdTPS in the resistance of S. sclarea to abiotic stresses. Our results suggested that abiotic stresses could induce the response and upregulation of SsdTPS expression and isoprenoid pathway in S. sclarea. Ectopic expression of SsdTPS conferred drought tolerance in transgenic Arabidopsis, compared with wild-type. Overexpression of SsdTPS enhanced the transcription of ABA signal transduction synthetic regulators and induced the positive feedback upregulating key regulatory genes in the MEP pathway, thereby promoting the increase of ABA content and improving drought tolerance in transgenic plants. In addition, SsdTPS-overexpressed transgenic Arabidopsis improved the responses of stomatal regulatory genes and ROS scavenging enzyme activities and gene expression to drought stress. This promoted the stomatal closure and ROS reduction, thus enhancing water retention capacity and reducing oxidative stress damage. These findings unveil the potentially positive role of SsdTPS in orchestrating multiple regulatory mechanisms and maintaining homeostasis for improved abiotic stress resistance in S. sclarea, providing a novel insight into strategies for promoting drought resistance and cultivating highly tolerant plants.

Gut microbiome changes in mouse, Mongolian gerbil, and hamster models following Clostridioides difficile challenge.

Introduction: Clostridioides difficile infection (CDI), as well as its etiology and pathogenesis, have been extensively investigated. However, the absence of suitable CDI animal models that reflect CDI symptoms and the associated gut microbiome changes in humans has limited research progress in this field. Thus, we aimed to investigate whether Mongolian gerbils, which present a range of human pathological conditions, can been used in studies on CDI. Methods: In this study, we infected Mongolian gerbils and two existing CDI model animals, mice and hamsters, with the hypervirulent ribotype 027 C. difficile strain, and comparatively analyzed changes in their gut microbiome composition via 16S rRNA gene sequencing. Methods: In this study, we infected Mongolian gerbils and two existing CDI model animals, mice and hamsters, with the hypervirulent ribotype 027 C. difficile strain, and comparatively analyzed changes in their gut microbiome composition via 16S rRNA gene sequencing. Results: The results obtained showed that C. difficile colonized the gastrointestinal tracts of the three rodents, and after the C. difficile challenge, C57BL/6J mice did not manifest CDI symptoms and their intestines showed no significant pathological changes. However, the hamsters showed explosive intestinal bleeding and inflammation and the Mongolian gerbils presented diarrhea as well as increased infiltration of inflammatory cells, mucus secretion, and epithelial cell shedding in their intestinal tissue. Further, intestinal microbiome analysis revealed significant differences with respect to intestinal flora abundance and diversity. Specifically, after C. difficile challenge, the Firmicutes/Bacteroidetes ratio decreased for C57BL/6J mice, but increased significantly for Mongolian gerbils and hamsters. Furthermore, the abundance of Proteobacteria increased in all three models, especially in hamsters, while that of Verrucomicrobia only increased significantly in C57BL/6J mice and Mongolian gerbils. Our results also indicated that differences in the relative abundances of Lactobacillaceae and Akkermansia were primarily responsible for the observed differences in response to C. difficile challenge. Conclusion: Based on the observed responses to C. difficile challenge, we concluded for the first time that the Mongolian gerbil could be used as an animal model for CDI. Additionally, the taxa identified in this study may be used as biomarkers for further studies on CDI and to improve understanding regarding changes in gut microbiome in CDI-related diseases.

Spatial distribution characteristics and degradation mechanism of microorganisms in n-hexadecane contaminated vadose zone.

The damage caused by petroleum hydrocarbon pollution to soil and groundwater environment is becoming increasingly significant. The vadose zone is the only way for petroleum hydrocarbon pollutants to leak from surface into groundwater. The spatial distribution characteristics of indigenous microorganisms in vadose zone, considering presence of capillary zones, have rarely been reported. To explore the spatial distribution characteristics of indigenous microorganisms in vadose zone contaminated by petroleum hydrocarbons, a one-dimensional column migration experiment was conducted using n-hexadecane as characteristic pollutant. Soil samples were collected periodically from different heights during experiment. Corresponding environmental factors were monitored online. The microbial community structure and spatial distribution characteristics of the cumulative relative abundance were systematically analyzed using 16S rRNA sequencing. In addition, the microbial degradation mechanism of n-hexadecane was analyzed using metabolomics. The results showed that presence of capillary zone had a strong retarding effect on n-hexadecane infiltration. Leaked pollutants were mainly concentrated in areas with strong capillary action. Infiltration and displacement of NAPL-phase pollutants were major driving force for change in moisture content (θ) and electric conductivity (EC) in vadose zone. The degradation by microorganisms results in a downward trend in potential of hydrogen (pH) and oxidation-reduction potential (ORP). Five petroleum hydrocarbon-degrading bacterial phyla and 11 degradable straight-chain alkane bacterial genera were detected. Microbial degradation was strong in the area near edge of capillary zone and locations of pollutant accumulation. Mainly Sphingomonas and Nocardioides bacteria were involved in microbial degradation of n-hexadecane. Single-end oxidation involved microbial degradation of n-hexadecane (C16H34). The oxygen consumed, hexadecanoic acid (C16H32O2) produced during this process, and release of hydrogen ions (H+) were the driving factors for reduction of ORP and pH. The vadose zone in this study considered presence of capillary zone, which was more in line with actual contaminated site conditions compared with previous studies. This study systematically elucidated vertical distribution characteristics of petroleum hydrocarbon pollutants and spatiotemporal variation characteristics of indigenous microorganisms in vadose zone considered presence of capillary zone. In addition, the n-hexadecane degradation mechanism was elucidated using metabolomics. This study provides theoretical support for development of natural attenuation remediation measures for petroleum-hydrocarbon-contaminated soil and groundwater.

Se-methylselenocysteine ameliorates mitochondrial function by targeting both mitophagy and autophagy in the mouse model of Alzheimer's disease.

Background: Alzheimer's disease (AD) exerts tremendous pressure on families and society due to its unknown etiology and lack of effective treatment options. Our previous study had shown that Se-methylselenocysteine (SMC) improved the cognition and synaptic plasticity of triple-transgenic AD (3 × Tg-AD) mice and alleviated the related pathological indicators. We are dedicated to investigating the therapeutic effects and molecular mechanisms of SMC on mitochondrial function in 3 × Tg-AD mice. Methods: Transmission electron microscopy (TEM), western blotting (WB), mitochondrial membrane potential (ΔΨm), mitochondrial swelling test, and mitochondrial oxygen consumption test were used to evaluate the mitochondrial morphology and function. Mitophagy flux and autophagy flux were assessed with immunofluorescence, TEM and WB. The Morris water maze test was applied to detect the behavioral ability of mice. Results: The destroyed mitochondrial morphology and function were repaired by SMC through ameliorating mitochondrial energy metabolism, mitochondrial biogenesis and mitochondrial fusion/fission balance in 3 × Tg-AD mice. In addition, SMC ameliorated mitochondria by activating mitophagy flux via the BNIP3/NIX pathway and triggering autophagy flux by suppressing the Ras/Raf/MEK/ERK/mTOR pathway. SMC remarkably increased the cognitive ability of AD mice. Conclusions: This research indicated that SMC might exert its therapeutic effect by protecting mitochondria in 3 × Tg-AD mice.

ACETATE RINGER'S SOLUTION VERSUS NORMAL SALINE SOLUTION IN SEPSIS: A RANDOMIZED, CONTROLLED TRIAL.

ABSTRACT: Background: Normal saline solution (NSS) and Ringer's acetate solution (RAS) are commonly given to critically ill patients as a fundamental fluid therapy. However, the effect of RAS and NSS on sepsis patient outcomes remains unknown. Methods: We conducted a single-center prospective open-label parallel controlled trial to enroll adult patients (>18 years old) diagnosed with sepsis. Participants received either RAS or NSS for intravenous infusion for 5 days. The primary outcome was the incidence of major adverse kidney events within 28 days (MAKE28). Secondary outcomes included 30-/90-day mortality, acute kidney injury, and hyperchloremia. The patients were then reclassified as NSS-only, RAS-only, and RAS + NSS groups according to the type of fluid they had received before enrollment. Thereafter, a secondary post hoc analysis was performed. Results: Two hundred fifty-five septic patients were screened, and 143 patients (51.0% in RAS group and 49.0% in NSS group) were enrolled in the study. Each group received a median of 2 L of fluid administration during five interventional days. Of the patients, 39.3% had received 500 mL (500-1,000 mL) of balanced salt solutions (BSSs) before intensive care unit (ICU) admission. There was no statistical difference among the RAS and NSS group on the primary outcome MAKE28 in the initial analysis (23.3% vs. 20.0%; OR, 1.2 [0.6 to 2.2]; P = 0.69). MAKE28 was observed in 23.3% of RAS-only versus 27.3% of NSS-only group patients (0.82 [0.35-1.94], P = 0.65) in the secondary post hoc analysis. The patients in the NSS-only group had a longer invasive mechanical ventilation days and a trend toward the accumulation of serum chloride. Conclusion: This study observed no statistically significant difference on MAKE28 and secondary outcomes among sepsis patients receiving RAS and NSS. However, it is unclear whether the large amount of fluid resuscitation before ICU admission and carrier NSS narrowed the difference between BSSs and NSSs.

Bulk and single-cell sequencing identified a prognostic model based on the macrophage and lipid metabolism related signatures for osteosarcoma patients.

The introduction of multidrug combination chemotherapy has significantly advanced the long-term survival prospects for osteosarcoma (OS) patients over the past decades. However, the escalating prevalence of chemoresistance has emerged as a substantial impediment to further advancements, necessitating the formulation of innovative strategies. Our present study leveraged sophisticated bulk and single-cell sequencing techniques to scrutinize the OS immune microenvironment, unveiling a potential association between the differentiation state of macrophages and the efficacy of OS chemotherapy. Notably, we observed that a heightened presence of lipid metabolism genes and pathways in predifferentiated macrophages, constituting the major cluster of OS patients exhibiting a less favorable response to chemotherapy. Subsequently, we developed a robust Macrophage and Lipid Metabolism (MLMR) risk model and a nomogram, both of which demonstrated commendable prognostic predictive performance. Furthermore, a comprehensive investigation into the underlying mechanisms of the risk model revealed intricate associations with variations in the immune response among OS patients. Finally, our meticulous drug sensitivity analysis identified a spectrum of potential therapeutic agents for OS, including AZD2014, Sapitinib, Buparlisib, Afuresertib, MIRA-1, and BIBR-1532. These findings significantly augment the therapeutic arsenal available to clinicians managing OS, presenting a promising avenue for elevating treatment outcomes.

The safety and efficacy of TACE combined with HAIC, PD-1 inhibitors, and tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: a retrospective study.

Objective: To assess the effectiveness and safety of transarterial chemoembolization (TACE) in combination with hepatic artery infusion chemotherapy (HAIC)、PD-1 inhibitors, and tyrosine kinase inhibitors(TKI) for unresectable hepatocellular carcinoma (HCC). Methods: A retrospective analysis was performed on 158 unresectable HCC patients admitted to the First Affiliated Hospital of Nanchang University between May 2019 and October 2022. The patients were split into two groups based on the type of treatment they received: TACE combined with HAIC,PD-1 and TKI group (THPK) and TACE combined with PD-1 and TKI group (TPK). The response was evaluated using modified solid tumor Efficacy Assessment Criteria (mRECIST). Kaplan-Meier curves were used to analyze the overall survival (OS). OS-influencing factors were identified using the Cox proportional risk regression model. Results: Finally, 63 patients who received THPK treatment and 60 patients who had TPK treatment were included. The THPK group had higher DCR (77.78% vs. 55.00%, P=0.007) and ORR (20.63% vs. 13.34%, P=0.282) than the TPK group did. The survival analysis curve also showed that the median OS was substantially longer in the THPK group than in the TPK group (OS: 21 months vs. 14 months, P=0.039). After multivariate Cox regression-corrected analysis, extrahepatic metastases (P=0.002) and methemoglobin >400 (P=0.041) were adverse influences on OS, but the THPK group (relative to the TPK group) was an independent favorable prognostic factor for OS (P=0.027). The results of the subgroup analysis showed that the addition of HAIC therapy to TPK treatment in patients with BCLC stage C, age ≦60 years, ECOG grade 0 and lobular distribution of tumors prolonged overall survival time and improved prognosis. Except for nausea, there was no difference in the adverse events between the two groups. Conclusion: In patients with unresectable HCC, the THPK group had a longer OS and similar adverse events compared to the TPK group. In the future, TACE-HAIC in combination with targeted and immunotherapy may be a more effective therapeutic option for hepatocellular carcinoma that cannot be surgically removed.

Study on medicinal food plants in the Gaoligongshan Biosphere Reserve, the richest biocultural diversity center in China.

BACKGROUND: Traditional knowledge associated with medicinal food plants (MFPs) plays a vital role in fighting hidden hunger and safeguarding the health of local people. MFPs resources are abundant in the Gaoligongshan area, a biosphere reserve with the richest biocultural diversity in China. Local people of different linguistic groups also have rich traditional botanical knowledge. However, there are still few comprehensive and systematic studies on MFPs there. METHODS: Ethnobotanical investigation including market survey, semi-structured interviews, free listing and key informant interviews was conducted in the Gaoligongshan area, Western Yunnan, Southwest China. A total of 13 local farmers' markets were selected and information about medicinal food plants, including food categories, medicinal and edible parts, modes of consumption, medicinal effects, and distribution were collected. The relative occurrence frequency (RFO) and cultural food significance index (CFSI) were calculated to identify the culturally significant MFPs. RESULTS: A total of 184 species of MFPs, belonging to 83 families, were collected in the Gaoligongshan area, including vegetables (77), medicinal diets (26), fruits (25), spices (18), herbal tea (13), tea substitutes (11), substitutes for staple food (8), nuts (5), oils and fats (4), and dye material (1). The most frequently used families were Fabaceae, Asteraceae and Apiaceae, with 11, 10, and 9 species, respectively. The most frequently used plant parts were the stems, followed by fruits and leaves. Based on the evaluation results of the CFSI and RFO indices, 18 species of MFPs with magnificent local cultural importance have been screened out, such as Houttuynia cordata, Eryngium foetidum, Sechium edule, Centella asiatica and Pseudocydonia sinensis. CONCLUSION: These findings have guiding significance for conservation of traditional knowledge associated with MFPs and facilitation of scientific utilization of MFPs to meet local people's needs for a healthy life.

Three New Species of Russulaceae (Russulales, Basidiomycota) from Southern China.

The characterization of natural fungal diversity impacts our understanding of ecological and evolutionary processes and can lead to novel bioproduct discovery. Russula and Lactarius, both in the order Russulales, represent two large genera of ectomycorrhizal fungi that include edible as well as toxic varieties. Based on morphological and phylogenetic analyses, including nucleotide sequences of the internal transcribed spacer (ITS), the 28S large subunit of ribosomal RNA (LSU), the second largest subunit of RNA polymerase II (RPB2), the ribosomal mitochondrial small subunit (mtSSU), and the translation elongation factor 1-α (TEF1-α) gene sequences, we here describe and illustrate two new species of Russula and one new species of Lactarius from southern China. These three new species are: R. junzifengensis (R. subsect. Virescentinae), R. zonatus (R. subsect. Crassotunicatae), and L. jianyangensis (L. subsect. Zonarii).

A hsa_circ_001726 axis regulated by E2F6 contributes to metastasis of hepatocellular carcinoma.

BACKGROUND: CircRNAs participate in the development of hepatocellular carcinoma (HCC). This work aims to explore the key tumor promoting circRNA as a gene therapy target. METHODS: The differentially expressed gene circRNAs in HCC tumor tissues was identified by mining GSE121714 dataset. EdU staining, wound healing, transwell invasion assay, TUNEL staining and western blotting examined proliferation, migration, invasion, apoptosis and epithelial mesenchymal transition (EMT). Xenograft mouse model and orthotopic transplantation tumor mouse model were constructed to verify the role of hsa_circ_001726 in growth and metastasis of HCC. The relationship among CCT2, E2F6, hsa_circ_001726, miR-671-5p and PRMT9 was identified by RNA-fluorescence in situ hybridization, luciferase reporter assay and RNA Immunoprecipitation. RESULTS: Eleven differentially expressed circRNAs were found in HCC tumors. Among them, hsa_circ_001726 was highly expressed in HCC tumors and cells, which was transcribed from CCT2. As a transcription factor of CCT2, E2F6 knockdown inactivated CCT2 promoter and reduced hsa_circ_001726 expression. Moreover, hsa_circ_001726 elevated PRMT9 expression by sponging miR-671-5p, and then activated Notch signaling pathway. Additionally, hsa_circ_001726 deficiency repressed malignant phenotypes of HCC cells, including proliferation, migration, invasion, EMT and apoptosis. In vivo, hsa_circ_001726 deficiency reduced tumor growth and lung metastasis of HCC in xenograft mouse models and orthotopic transplantation tumor mouse models. CONCLUSION: Hsa_circ_001726 functioned as an oncogene in HCC, which was derived from CCT2 and regulated by E2F6. Hsa_circ_001726 elevated PRMT9 expression by sponging miR-671-5p, and then activated Notch signaling pathway, thereby accelerating malignant phenotypes of HCC. Therefore, targeting hsa_circ_001726 may be a new avenue for HCC treatment.

Utilizing fNIRS to investigate the impact of Baduanjin training on attentional function in post-stroke cognitive impairment patients: a study protocol for a randomized controlled trial.

BACKGROUND: Post-stroke cognitive impairment (PSCI) is a prevalent complication among stroke survivors. It not only directly impacts patients' cognitive abilities but also hampers their capacity to regain independence in daily activities, consequently diminishing their quality of life. Among the various cognitive deficits following stroke, impaired attention is the most frequently observed, influencing not only daily functioning but also higher cognitive functions like working memory, executive functioning, and language.Emerging evidence indicates that Baduanjin, a traditional Chinese exercise, may have a positive impact on enhancing attention in older adults with mild cognitive impairment and stroke survivors. However, the precise mechanisms behind this effect remain unclear. In this study, we employed Baduanjin training as an intervention to address attention decline in post-stroke cognitive impairment patients and to delve into the potential mechanisms through which Baduanjin training may enhance attention in individuals with PSCI. METHODS: In this prospective randomized controlled trial, we plan to recruit 72 participants diagnosed with post-stroke cognitive impairment (PSCI). These participants will be randomly assigned in a 1:1:1 ratio to one of three groups: Baduanjin training(left hemisphere stroke and right hemisphere stroke) and conventional treatment.The conventional treatment group will receive standard rehabilitation sessions. In addition to conventional treatment, participants in the octogenarian training groups will undergo octogenarian training sessions lasting 40 min, five times a week, over a total period of 12 weeks.The primary outcome measures will include the Montreal Cognitive Assessment (MoCA) scale and the Attentional Lateralization Index. These assessments will be conducted by a trained evaluator before the start of the intervention and at weeks 6 and 12 after the intervention begins.Secondary outcome measures will be assessed using the baseline Mandarin version of the Oxford Cognitive Screening (OCS-P) scale, the simplified Fugl-Meyer Motor Function Assessment (FMA) scale, the Pittsburgh Rehabilitation Participation (PRPS) scale, and the Activities of Daily Living (ADL) scale before and after the intervention, respectively. DISCUSSION: This trial aims to examine the impact of Baduanjin training on attentional lateralization among patients with post-stroke cognitive impairment (PSCI). Functional brain imaging utilizing near-infrared spectroscopy will be employed to investigate how Baduanjin exercise influences the structural and functional connectivity of distinct brain regions or brain networks. TRIAL REGISTRATION: Chictr.org.cn, ID: ChiCTR2300076533 . Registered on 11 October 2023.