A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.

ObjectiveBased on the TCM theory of "Yang transforms materials to Qi while Yin constitutes material form"， this paper explored the effects of Zuogui Wan and Yougui Wan on the molecular mechanism of mitochondrial biogenesis during the adipogenic differentiation process of rat bone marrow mesenchymal stem cells （BMSCs） by mediating peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） and peroxisome proliferators-activated receptor γ （PPARγ）， providing theoretical support for the prevention and treatment of postmenopausal osteoporosis （PMOP） using Zuogui Wan and Yougui Wan. MethodsBMSCs were divided into a blank group， Zuogui Wan （ZGW） group， Yougui Wan （YGW） group， and Progynova group. Cell identification was performed using flow cytometry. The growth curves of BMSCs were plotted using the methylthiazolyldiphenyl-tetrazolium bromide （MTT） method， and the effects of Zuogui Wan and Yougui Wan on the proliferation of BMSCs were detected. The Oil red O staining method was used to detect lipid droplet formation. The Western blot method was used to detect the expression of adipogenesis-related factors PPARγ， CCAAT/enharcer-binding protein （C/EBP）α， C/EBPβ， lipoprotein lipase （LPL） protein， brown adipose tissue-related （BAT） proteins PGC-1α， uncoupcing protein 1 （UCP1）， PR domdin-containing protein 16 （PRDM16）， mitochondrial biogenesis-related PGC-1α， nuclear respiratory factor 1 （Nrf1）， nuclear factor E₂-related factor 2 （Nrf2）， and mitochondrial transcription factor A （TFAM）. The expression of adipogenesis-related factors PPARγ， C/EBPα， C/EBPβ， LPL genes， and the copy number of cytochrome B （CytoB mtDNA） gene was detected using real-time polymerase chain reaction （Real-time PCR）. Mitochondrial ultrastructure was detected using transmission electron microscopy. ResultsCompared with that in the blank group， the proliferation ability of BMSCs in each treatment group increased continuously as the intervention progressed， and lipid droplets significantly decreased after the drug intervention. The mRNA and protein expression levels of adipogenesis-related factors PPARγ， C/EBPα， C/EBPβ， and LPL were significantly downregulated （P<0.01）， while those of the BAT-related factors PGC-1α， UCP1， PRDM16 were significantly upregulated （P<0.01）. The number of mitochondria increased， accompanied by reduced swelling. The double membrane and cristae structure were clear， and the internal cristae rupture was reduced. The copy number of CytoB mtDNA in each treatment group was significantly increased （P<0.01）. The protein expression levels of mitochondrial biogenesis-related PGC-1α， Nrf1， Nrf2， and TFAM in each treatment group were significantly increased （P<0.01）. ConclusionBoth Zuogui Wan and Yougui Wan can prevent and treat PMOP by intervening in mitochondrial biogenesis in BMSCs through PGC-1α/PPARγ.

Objective: The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls. Methods: Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans. Results: Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase. Conclusion These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.

Objective: The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls. Methods: Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans. Results: Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase. Conclusion These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.

Objective: The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls. Methods: Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans. Results: Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase. Conclusion These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.

Objective: The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls. Methods: Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans. Results: Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase. Conclusion These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.

Objective: The purpose of this study was to explore the capacity for energy production under conditions of increased energy demand in schizophrenia (SCZ) subjects compared to healthy controls. Methods: Twelve healthy controls (33.00±6.07 years) and 12 subjects diagnosed with SCZ or schizoaffective disorder (36.00±8.33 years) matched for age and sex, were recruited for this study. Hypoxic stress was induced during MR scans to elevate the energy demand on the subjects’ bioenergetic systems. Participants breathed air with a lower oxygen concentration (FiO2=13%), maintaining their SpO2 levels (86%) during the initial phase of the scan. 31Phosphorus MR spectroscopy was employed to examine metabolite levels, including phosphocreatine (PCr), β-adenosine triphosphate (ATP), and inorganic phosphate (Pi), as well as the ratios of PCr/Pi and PCr/β-ATP, in regions such as the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and posterior cortex (POC), as well as across the entire brain, during both hypoxia and hyperoxia scans. Results: Subjects with SCZ had significantly lower levels of Pi across the brain and particularly, in the PFC, POC, and ACC during the hypoxia scan. Moreover, levels of PCr/Pi, indicative of mitochondrial energy production, were found to be higher in the same brain regions in the SCZ group. No significant differences were found in hyperoxia scan phase. Conclusion These findings suggest a deficit in the bioenergetic systems of individuals with SCZ under conditions of heightened energy demand. Further studies are warranted.

Cervi Cornu Pantotrichum is a precious animal-derived Chinese medicinal material, while there are often adulterants derived from animals not specified in the Chinese Pharmacopeia in the market, which disturbs the safety of medication. This study was conducted with the aim of strengthening the quality control of Cervi Cornu Pantotrichum and standardizing the medication. To achieve digital identification of Cervi Cornu Pantotrichum from different sources, a digital identification model was constructed based on ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UHPLC-QTOF-MS~E) combined with an adaptive boosting algorithm(Adaboost). The young furred antlers of sika deer, red deer, elk, and reindeer were processed and then subjected to polypeptide analysis by UHPLC-QTOF-MS~E. Then, the mass spectral data reflecting the polypeptide information were obtained by digital quantification. Next, the key data were obtained by feature screening based on Gini index, and the digital identification model was constructed by Adaboost. The model was evaluated based on the recall rate, F_1 composite score, and accuracy. Finally, the results of identification based on the constructed digital identification model were validated. The results showed that when the Gini index was used to screen the data of top 100 characteristic polypeptides, the digital identification model based on Adaboost had the best performance, with the recall rate, F_1 composite score, and accuracy not less than 0.953. The validation analysis showed that the accuracy of the identification of the 10 batches of samples was as high as 100.0%. Therefore, based on UHPLC-QTOF-MS~E and Adaboost algorithm, the digital identification of Cervi Cornu Pantotrichum can be realized efficiently and accurately, which can provide reference for the quality control and original animal identification of Cervi Cornu Pantotrichum.
Animals ; Algorithms ; Antlers/chemistry* ; Boosting Machine Learning Algorithms ; Chromatography, High Pressure Liquid/methods* ; Deer ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Quality Control ; Reindeer ; Tandem Mass Spectrometry/methods* ; Tissue Extracts/analysis*

To investigate the effects of phosphorus fertilizer on the morphological traits, active ingredients and rhizosphere soil microbial community of Polygala tenuifolia. The phosphorus fertilizer was calculated in terms of P_2O_5. Five treatments were set up: 0(CK), 17(P1), 34(P2), 51(P3), and 68(P4) kg per Mu(1 Mu≈667 m~2). A randomized block design was adopted. Samples of P. tenuifolia and its rhizosphere soil were collected under different superphosphate fertilizer treatments. Illumina high-throughput sequencing was used to analyze the rhizosphere soil microbial community, 9 morphological traits were measured and the content of 11 active ingredients were determined. The results showed that the whole plant weight, shoot fresh weight, root weight, and root peel thickness were the highest under P1 treatment, increasing by 34.41%, 38.80%, 39.21%, and 3.17% respectively compared to CK. Under P2 treatment, the plant height, stem diameter, root thickness, and core thickness were significantly higher than CK. Phosphorus fertilizer had a significant impact on the content of tenuifolin, sibiricose A5, sibiricose A6, arillanin A, 3,6'-disinapoyl sucrose, and polygalaxanthone Ⅲ. Correlation analysis results showed that the relative abundance of Arthrobacter, Bacillus, norank＿f＿Vicinamibacteraceae, norank＿o＿Vicinamibacterales, MND1 and other bacteria, as well as the relative abundance of Neocosmospora, Paraphoma and other fungi were positively correlated with root diameter, wood core diameter, the whole plant weight, root weight, shoot fresh weight of P. tenuifolia. Bacillus, Neocosmospora, Subulicystidium were significantly positively correlated with oligosaccharides such as 3,6'-disinapoyl sucrose, sibiricose A5、sibiricose A6、glomeratose A、arillanin A and tenuifoliside C. Arthrobacter, Humicola, Aspergillus, Paraphoma were positively correlated with tenuifolin and norank＿f＿Vicinamibacteraceae, norank＿o＿Vicinamibacterales, Fusarium were positively correlated with polygalaxanthone Ⅲ. Evidently, appropriate phosphorus application is conducive to the growth and quality improvement of P. tenuifolia, and can increase the abundance of beneficial microorganisms in the soil.
Rhizosphere ; Phosphorus/pharmacology* ; Soil Microbiology ; Polygala/anatomy & histology* ; Fertilizers/analysis* ; Bacteria/metabolism* ; Soil/chemistry* ; Microbiota/drug effects* ; Plant Roots/metabolism*

OBJECTIVE: To investigate the variability of bone metabolism levels among different populations and its association with knee osteoarthritis (KOA) pain. METHODS: A total of 50 people (control group) who participated in physical examination from January 2023 to June 2023 were selected, including 26 males and 24 females, wtih a mean aged of (52.14±9.04) years old ranging 41 to 65 years old. The other 50 patients with knee osteoarthritis(case group) who attended the outpatient clinic of the Orthopedics and Traumatology Department in the same time period, including 19 males and 31 females, with a mean age of (53.60±7.76) years old ranging 40 to 65 years. The two groups of Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC) and bone metabolism markers, such as 25-hydroxy-cholecalciferol[25(OH)D], β-isomerized typeⅠcollagen C-telopeptide breakdown products (β-CTX), total typeⅠprocollagen N-terminal propeptide (t-PINP), osteocalcin (OC), parathormone (PTH) levels were compared. Pearson correlation analysis was used to compare the correlation between two groups of bone metabolism related markers and WOMAC. RESULTS: The WOMAC score of the case group (39.90±2.34) was higher than that of the control group (3.60±0.57), with significant difference (P<0.05). There was no significant difference between the two groups of 25 (OH)D, β-CTX and PTH (P>0.05). The t-PINP and OC of the case group were (62.90±52.40) and (19.88±10.15) ng·ml-1, respectively, and those of the control group were (38.86±10.82) and (14.90±3.62) ng·ml^-1, respectively;the t-PINP and OC of the case group were higher than those of the control group, with significant difference (P<0.05). Pearson correlation analysis showed that t-PINP was positively correlated with WOMAC pain score in the case group (r²=0.045, P<0.01). CONCLUSION Bone metabolism levels in the serum of patients with knee osteoarthritis are different from those of healthy people, and the difference between OC and t-PINP is the most obvious, and the concentration of t-PINP levels is positively correlated with pain symptoms in patients with KOA. However, the specific mechanism of correlation between the bone metabolism levels of patients with KOA and their pain symptoms needs to be further elucidated by basic experimental research as well as by enlarging the samples.
Humans ; Female ; Male ; Middle Aged ; Osteoarthritis, Knee/metabolism* ; Aged ; Adult ; Bone and Bones/metabolism* ; Pain/etiology* ; Biomarkers/metabolism*