Socioeconomic disparities and regional environment are associated with cervical lymph node metastases in children and adolescents with differentiated thyroid cancer: developing a web-based predictive model.

Purpose: To establish an online predictive model for the prediction of cervical lymph node metastasis (CLNM) in children and adolescents with differentiated thyroid cancer (caDTC). And analyze the impact between socioeconomic disparities, regional environment and CLNM. Methods: We retrospectively analyzed clinicopathological and sociodemographic data of caDTC from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2019. Risk factors for CLNM in caDTC were analyzed using univariate and multivariate logistic regression (LR). And use the extreme gradient boosting (XGBoost) algorithm and other commonly used ML algorithms to build CLNM prediction models. Model performance assessment and visualization were performed using the area under the receiver operating characteristic (AUROC) curve and SHapley Additive exPlanations (SHAP). Results: In addition to common risk factors, our study found that median household income and living regional were strongly associated with CLNM. Whether in the training set or the validation set, among the ML models constructed based on these variables, the XGBoost model has the best predictive performance. After 10-fold cross-validation, the prediction performance of the model can reach the best, and its best AUROC value is 0.766 (95%CI: 0.745-0.786) in the training set, 0.736 (95%CI: 0.670-0.802) in the validation set, and 0.733 (95%CI: 0.683-0.783) in the test set. Based on this XGBoost model combined with SHAP method, we constructed a web-base predictive system. Conclusion: The online prediction model based on the XGBoost algorithm can dynamically estimate the risk probability of CLNM in caDTC, so as to provide patients with personalized treatment advice.

Monkeypox: An outbreak of a rare viral disease.

Monkeypox is a viral zoonotic disease rarely found outside Africa. Monkeypox can be spread from person to person through close contact with an infected person, and the rate of transmission is not very high. In addition, monkeypox and variola virus are both pox viruses, and the spread of monkeypox virus was also controlled to some extent by the smallpox campaign, so monkeypox was not widely paid attention to. However, as smallpox vaccination is phased out in various countries or regions, people's resistance to orthopoxviruses is decreasing, especially among people who have not been vaccinated against smallpox. This has led to a significant increase in the frequency and geographical distribution of human monkeypox cases in recent years, and the monkeypox virus has become the orthopoxvirus that poses the greatest threat to public health. Since the last large-scale monkeypox infection was detected in 2022, the number of countries or territories affected has exceeded 100. Many confirmed and suspected cases of monkeypox have been found in individuals who have not travelled to affected areas, and the route of infection is not obvious, making this outbreak of monkeypox a cause for concern globally. The purpose of this systematic review is to further understand the pathophysiological and epidemiological characteristics of monkeypox, as well as existing prevention and treatment methods, with a view to providing evidence for the control of monkeypox.

Acrylamide-Induced Hepatotoxicity Through Oxidative Stress: Mechanisms and Interventions.

Significance: Acrylamide (AA) widely exists in the environment. Studies have demonstrated that AA has neurotoxicity and potential carcinogenicity in humans, and genotoxicity and severe hepatotoxicity in animals. As the critical metabolism organ, the liver is the primary attacking target of AA. This review summarizes the recent advances in hepatotoxicity mechanism through AA-induced oxidative stress in rodent livers and hepatic cell lines, and this is beneficial to assess the risks of AA exposure and explore effective intervention methods for AA hepatotoxicity. Recent Advances: Accumulating evidence has indicated that AA-induced oxidative stress is responsible for its hepatotoxicity. The changes in homological and biochemical indexes such as activities of hepatic antioxidant enzymes have been elucidated with the occurrence and development of oxidative stress. Also, the molecular mechanisms underlying AA-induced hepatotoxicity through oxidative stress have been mainly explained by apoptosis, inflammatory, and autophagic pathways. Critical Issues: This review is focusing on the molecular mechanism of hepatotoxicity through AA-induced oxidative stress, and this can provide a theoretical basis for the assessment of AA-induced health risk and finding potential intervention targets. Future Directions: Epigenetic modifications such as microRNAs (miRNAs) and modulation of the gut microbiome involved in the AA toxification pathway must be investigated, and they will provide novel insights to unravel the toxification mechanism and intervention strategy for AA hepatotoxicity. Antioxid. Redox Signal. 38, 1122-1137.

Causal association between obesity and hypothyroidism: a two-sample bidirectional Mendelian randomization study.

Introduction: Previous observational studies have reported a positive correlation between obesity and susceptibility to hypothyroidism; however, there is limited evidence from alternative methodologies to establish a causal link. Methods: We investigated the causal relationship between obesity and hypothyroidism using a two-sample bidirectional Mendelian randomization (MR) analysis. Single-nucleotide polymorphisms (SNPs) associated with obesity-related traits were extracted from a published genome-wide association study (GWAS) of European individuals. Summarized diagnostic data of hypothyroidism were obtained from the UK Biobank. Primary analyses were conducted using the inverse variance-weighted (IVW) method with a random-effects model as well as three complementary approaches. Sensitivity analyses were performed to ascertain the correlation between obesity and hypothyroidism. Results: MR analyses of the IVW method and the analyses of hypothyroidism/myxedema indicated that body mass index (BMI) and waist circumference (WC) were significantly associated with higher odds and risk of hypothyroidism. Reverse MR analysis demonstrated that a genetic predisposition to hypothyroidism was associated with an increased risk of elevated BMI and WC, which was not observed between WC adjusted for BMI (WCadjBMI) and hypothyroidism. Discussion: Our current study indicates that obesity is a risk factor for hypothyroidism, suggesting that individuals with higher BMI/WC have an increased risk of developing hypothyroidism and indicating the importance of weight loss in reducing the risk of hypothyroidism.

Influence of Seasonings and Spice Essential Oils on Acrylamide Production in a Low Moisture Model System.

Acrylamide (AA) is a typical contaminant produced during the heating process. In the present study, two seasonings (soy sauce and rice vinegar) and three spice essential oils (chive, ginger, and pepper) were added to the asparagine (Asn)/glucose (Glc) diethylene glycol model system to investigate the production of AA in a low moisture model system. The generation of AA was significantly enhanced when low levels of soy sauce (1% and 3% v/v) were added (p < 0.05). The Asn/Glc model system was heated for 15 min with 0%, 1%, or 3% (v/v) soy sauce, containing 43 mg/L, 63 mg/L, and 53 mg/L AA, respectively. However, the addition of a high level of soy sauce (5% v/v) showed significant inhibition of AA production after heating for 10 min (p < 0.05). About 36% of AA was inhibited in the Asn/Glc/soy sauce (5%) model system after heating for 15 min. The addition of low levels of rice vinegar (1% and 3% v/v) showed comprehensive effects on AA production. Nevertheless, the addition of rice vinegar at 5% v/v had an inhibitory effect on AA generation (p < 0.05). All kinds of spice essential oils promoted the production of AA (p < 0.05). There was a dose−response relationship between the level of spice essential oils and the generation of AA. This study proposes the importance of seasonings and spice essential oils for AA production in food preparation.

Pan-cancer analysis identifies migrasome-related genes as a potential immunotherapeutic target: A bulk omics research and single cell sequencing validation.

Introduction: The migrasome is a newly discovered organelle that resembles extracellular vesicles in structure. However, the function of the migrasome in tumors, particularly in relation to tumor immunity and tumor microenvironment, is unclear. Methods: Gene expression data, copy number variation raw data, and methylation data of 33 cancer types were downloaded from The Cancer Genome Atlas database. Immunohistochemistry (IHC) based on 114 case of colorectal cancer was used to validate the expression of the migrasome hub-gene. We analyzed the expression, prognosis, genetic variation, and drug sensitivity profiles of migrasome-related genes (MRGs) in pan-cancer datasets. A migrasome score was constructed based on gene set enrichment analysis, and the correlation of migrasomes with the tumor microenvironment was assessed. The CancerSEA was used to perform a single-cell level functional analysis of the migrasome. Additionally, we also analyzed the correlation between migrasomes and tumor mutational burden (TMB), microsatellite instability (MSI), and tumor immune dysfunction and exclusion scores. Single-cell transcriptome sequencing (scRNA-seq) data was used to assess the activation state of migrasomes in the tumor microenvironment. Results: PIGK expression was significantly up-regulated in 22 of 33 tumors, and high expression of migrasome was estimated to have contributed to poor prognosis. Missense mutations are the most common type of mutation in MRGs. We identified piperlongumine as a potential drug targeting migrasomes. The migrasome score was significantly and positively correlated with the tumor immunity score and the stroma score. In most tumors, the abundance of macrophages in the tumor microenvironment was significantly and positively correlated with the migrasome score. Additionally, the migrasome scores were significantly correlated with the immune checkpoint genes in pan-cancer as well as immune checkpoint therapy-related markers including TMB and MSI. According to scRNA-seq analysis, migrasome differed significantly among cells of the tumor microenvironment. IHC confirmed low expression of ITGA5 and PIGK in colorectal cancer. Discussion: We performed the first pan-cancer analysis of migrasomes and discovered that they play an important role in tumor development and immune escape. Our study provides new insights into the role of migrasomes in tumor prognosis and immunotherapy.

Jiawei Yanghe Decoction Regulates Bone-Lipid Balance through the BMP-SMAD Signaling Pathway to Promote Osteogenic Differentiation of Bone Mesenchymal Stem Cells.

Background: The Jiawei Yanghe decoction (JWYHD) is a traditional Chinese medicine formula for the treatment of osteoporosis, but its therapeutic mechanism has not been fully elucidated, and the therapeutic target of the intervention disease needs to be further verified. The dysfunction of bone mesenchymal stem cells (BMSCs) is considered to be an important pathogenesis of postmenopausal osteoporosis (PMOP). The purpose of this study was to explore how JWYHD regulates BMSC differentiation through the BMP-SMAD signal pathway. Methods: In the in vivo study, we used an ovariectomized PMOP rat (n = 36, 2-month-old, 200 ± 20 g) model and femur micro-CT analysis to study the effect of JWYHD on bone loss in rats. By immunofluorescence, the translocation expression of BMP2, a key protein in the pathway, was detected. Serum bone metabolism was detected by an enzyme-linked immunosorbent assay (ELISA). Alkaline phosphatase (ALP) activity was detected by alkaline phosphatase staining (ALPS), osteogenesis and matrix mineralization were detected by alizarin red staining (ARS), the adipogenic ability of BMSCs was detected by oil red staining (ORS), and CFU is used to detect the ability of cells to form colonies. The expression of related proteins was detected by western blotting. Results: In vivo and in vitro, the OP phenotypes of SD rats induced by ovariectomy (OVX) included impaired bone mineral density and microstructure, abnormal bone metabolism, and impaired MSC differentiation potential. JWYHD treatment reversed this trend and restored the differentiation potential of MSCs. JWYHD medicated serum and direct intervention of drugs activated the BMP-SMAD signaling pathway, promoted the osteogenic differentiation of BMSCs, and inhibited their adipogenic differentiation. Conclusions: Our data identified that JWYHD is an effective alternative drug for the treatment of PMOP that functions to stimulate the differentiation of BMSCs into osteoblasts in the BMP-SMAD signaling-dependent mechanism.

Blueberry Anthocyanins Extract Attenuates Acrylamide-Induced Oxidative Stress and Neuroinflammation in Rats.

Acrylamide (AA) is a widespread environmental and dietary-derived neurotoxin, which can induce oxidative stress and associated inflammation in the brain. Anthocyanins widely occur as natural antioxidant and anti-inflammatory phytochemicals. Herein, the protective effects of blueberry anthocyanins extract (BAE) against AA-induced neurotoxicity were investigated in rats. The rats were pretreated with BAE (175 mg/kg body weight/day) by oral gavage for the first 7 days, followed by the co-administration of BAE and AA (35 mg/kg body weight/day) by oral gavage for the next 12 days. Results showed that BAE significantly decreased the malondialdehyde (MDA) production, and increased glutathione (GSH) and antioxidant enzyme levels; and it also suppressed microglial activation, astrocytic reaction, and pro-inflammatory cytokine expressions. Furthermore, BAE elevated the extracellular signal-related kinase (ERK)/cAMP response elements binding protein (CREB)/brain-derived neurotrophic factor (BDNF) pathway, and relieved the accumulation of amyloid beta (Aß) 1-42 and 1-40 after AA exposure. Consequently, AA-induced neuronal necrosis and downregulation of synaptosomal-associated protein 25 (SNAP-25) were attenuated by BAE in the hippocampus and cerebral cortex. In conclusion, BAE can exert a protective function on neurons and synapses against AA-induced oxidative stress and neuroinflammation.

2-(Naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone induces apoptosis via ROS-mediated MAPK, AKT, and STAT3 signaling pathways in HepG2 human hepatocellular carcinoma cells.

1,4-naphthoquinone and its derivatives have attracted widespread attention due to their multiple biological activities, such as induction of cancer cell apoptosis; however, most of these compounds have high cytotoxicity. In this study, in order to reduce their toxicity and increase their potential anti-tumor effects, we synthesized a novel 1,4-naphthoquinone derivative named 2-(naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone (NTDMNQ), and investigated its apoptotic effects and underlying mechanism. Our results showed that NTDMNQ inhibited the viability of HepG2, Hep3B, and Huh7 human hepatocellular carcinoma (HCC) cells. It also increased the accumulation of cells in the G0/G1 phase of the cell cycle by increasing the expression levels of p-p53, p21 and p27, while decreasing the levels of Cyclin D1, Cyclin E, Cyclin-dependent kinase 2 (CDK2), CDK4, and CDK6. Inhibition of reactive oxygen species (ROS) by the ROS scavenger N-acetyl-L-cysteine (NAC) decreased apoptosis in NTDMNQ-treated cells. Western blot analysis showed that NTDMNQ increased the phosphorylation of p38 and c-Jun N-terminal kinase (JNK), and decreased the phosphorylation of extracellular signal-regulated kinase (ERK), AKT, and signal transducer and activator of transcription-3 (STAT3); these effects were blocked by NAC. Both the JNK inhibitor (SP600125) and p38 inhibitor (SB203580) reversed the phosphorylation of STAT3, and the ERK inhibitor (FR180204) and AKT inhibitor (LY294002) reduced the expression of STAT3. Taken together, these findings suggest that NTDMNQ induces apoptosis via ROS-mediated MAPK, AKT and STAT3 signaling pathways in HepG2 cells, and may be a potent anticancer agent.

Influence of citral on acrylamide formation in model systems.

This work aimed to evaluate the role of citral (Cit) in the formation of acrylamide (AA) in model systems. The asparagine (Asn)/glucose (Glc), Asn/Glc/ginger essential oil (GEO), and Asn/Glc/Cit model systems were prepared and analysed by UPLC-MS/MS. Cit was implicated to be a major product that contributed to the enhancement of AA formation by GEO. The addition of Cit significantly enhanced the formation of AA in the Asn/Glc model system in a dose-dependent manner. Further analysis showed Cit rather than its oxidation product played a major role in AA formation. Cit not only directly reacted with Asn via the Maillard reaction producing AA but also promoted the formation of AA between Asn and Glc.

The simultaneous inhibition of histidine on 5-hydroxymethylfurfural and acrylamide in model systems and cookies.

5-Hydroxymethylfurfural (HMF) and acrylamide (AA) are neoformed food contaminants. In this study, the simultaneous inhibition of HMF and AA by histidine (His) were investigated. In the asparagine (Asn)/glucose (Glc) model system, the inhibition ratios of HMF and AA were in the range of 28-58% and 0-71% when 20 mmol/L His was added. In cookies, His also exhibited excellent inhibition effects on both HMF and AA. At the His concentration of 2% (w/w), the inhibition ratios of HMF and AA reached 90% and 65%. Additionally, the sensory quality of cookies was not affected significantly. Qualitative results suggested that His inhibited the formation of AA by the competitive reaction between His and Asn for Glc, as well as directly eliminated the formed HMF and AA via the carbonyl-amine reaction and the Michael addition, respectively. This study revealed that His could be applied for the inhibition of HMF and AA in heated food.

MiR-27a-5p regulates acrylamide-induced mitochondrial dysfunction and intrinsic apoptosis via targeting Btf3 in rats.

Acrylamide (AA), a potential carcinogen, is commonly formed in foods rich in carbohydrates at high heat. It is known that AA-induced mitochondrial dysfunction is responsible for its toxicity. Previously we found AA exposure increased miR-27a-5p expression in livers of SD rats. Here, the regulation mechanism of miR-27a-5p in mitochondrial dysfunction was investigated in rat liver cell lines (IAR20) and SD rats. The results showed that the overexpressed miR-27a-5p contributes to modulating mitochondrial dysfunction and Btf3 is identified as its target gene. The knockdown of Btf3 increases the cleaved PARP1 level and the phosphorylation of ATM and p53, which results in mitochondria-dependent apoptosis. Therefore, the miR-27a-5p-Btf3-ATM-p53 axis might play a vital role in the promotion of AA-induced cell apoptosis through disrupting mitochondrial structure and function. This would provide a potential target for the assessment and intervention of AA toxicity.

Triacylglycerol and Fatty Acid Compositions of Blackberry, Red Raspberry, Black Raspberry, Blueberry and Cranberry Seed Oils by Ultra-Performance Convergence Chromatography-Quadrupole Time-of-Flight Mass Spectrometry.

The triacylglycerol (TAG) compositions of blackberry, red raspberry, black raspberry, blueberry and cranberry seed oils were examined using ultra-performance convergence chromatography-quadrupole time-of-flight mass spectrometry (UPC2-QTOF MS). A total of 52, 53, 52, 59 and 58 TAGs were detected and tentatively identified from the blackberry, red raspberry, black raspberry, blueberry and cranberry seed oils, respectively, according to their accurate molecular weight in MS1 and fragment ion profiles in MS2. OLL was the most abundant TAG in the blackberry, red raspberry and black raspberry seed oils. Furthermore, the fatty acid compositions of the five berry seed oils were directly determined by gas chromatography coupled with mass spectrometry (GC-MS). In addition, the seed oils had total phenolic contents ranging 13.68-177.06 µmol GAE (gallic acid equivalent)/L oil, and significant scavenging capacities against DPPH, peroxyl, and ABTS+ radicals. These results indicated that the combination of UPC2 and QTOF MS could effectively identify and semi-quantify the TAGs compositions of the berry seed oils with sn-position information for the fatty acids. Understanding the TAGs compositions of these berry seed oils could improve the utilization of these potentially high nutritional value oils for human health.

Active and Robust Composite Films Based on Gelatin and Gallic Acid Integrated with Microfibrillated Cellulose.

BACKGROUND: Gelatin is a renewable, biodegradable, and inexpensive food polymer. The insufficient mechanical and functional properties of gelatin-based films (GBF) restrict their commercial application in food packaging. This work proposed a facile strategy to prepare an active and robust GBF that has the potential to be used in food packaging. METHODS: A strong and active GBF was prepared based on the principle of supramolecular chemistry via the incorporation of gallic acid (GA) as an active crosslinking agent and of microfibrillated cellulose (MFC) as a reinforcing agent. RESULTS: Under the appropriate concentration (1.0 wt%), MFC was evenly dispersed in a gelatin matrix to endow the film with low surface roughness and compact structure. Compared with the GF, the tensile strength and elongation at break of the resultant film reached 6.09 MPa and 213.4%, respectively, representing the corresponding improvement of 12.8% and 27.6%. Besides, a significantly improved water vapor barrier (from 3.985 × 10-8 to 3.894 × 10-8 g·m-1·Pa-1·s-1) and antioxidant activity (from 54.6% to 86.4% for ABTS radical scavenging activity; from 6.0% to 89.1% for DPPH radical scavenging activity) of GBFs were also observed after introducing the aromatic structure of GA and nano-/microfibrils in MFC. Moreover, the UV blocking performance and thermal stability of GGF and GGCFs were also enhanced. CONCLUSIONS: this work paves a promising way toward facile preparation of multifunctional GBFs that have great potential to be used in fabricating active and safe food packaging materials for food preservation.

18ß-Glycyrrhetinic Acid Has Anti-Cancer Effects via Inducing Apoptosis and G2/M Cell Cycle Arrest, and Inhibiting Migration of A549 Lung Cancer Cells.

BACKGROUND: 18ß-glycyrrhetinic acid (18ß-Gly), which is extracted from licorice root, has various pharmacological properties; however, its anti-cancer effects on lung cancer cells have not been fully established. PURPOSE: In this study, we investigated the underlying molecular mechanisms of 18ß-Gly. RESULTS: Our results showed that 18ß-Gly had significant cytotoxic effects and no apparent side effects. 18ß-Gly induced mitochondria-dependent apoptosis of A549 lung cancer cells. In addition, after treatment with 18ß-Gly, intracellular reactive oxygen species (ROS) levels were significantly increased, and G2/M cell cycle arrest and inhibition of cell migration were induced via the mitogen-activated protein kinase (MAPK)/signal transducer and activator of transcription 3 (STAT3)/nuclear factor kappa (NF-κB) signaling pathways. After pretreatment with the ROS scavenger N-acetyl-L-cysteine or MAPK inhibitors, the expression levels of phosphorylated p38 (p-p38), phosphorylated c-Jun N-terminal kinase, inhibitor of nuclear factor kappa B, cleaved caspase-3 (cle-cas-3), cleaved poly (ADP ribose) polymerase (cle-PARP), p-p53, p27, p21, and E-cadherin were decreased; and levels of phosphorylated extracellular signal-regulated kinase, p-STAT3, NF-κB, Bcl-2, cyclin B1, cyclase-dependent kinase 1/2 (CDK1/2), N-cadherin, vimentin, and snail homolog 1 (SNAI 1) were increased. In addition, the percentage of cells in the G2/M phase was decreased, and inhibition of migration was reduced. CONCLUSION: In summary, 18ß-Gly induced apoptosis and G2/M cell cycle arrest and inhibited migration via the ROS/MAPK/STAT3/NF-κB signaling pathways in A549 lung cancer cells. Therefore, 18ß-Gly is a novel promising candidate for the treatment of lung cancer.

Acrylamide Induces Abnormal mtDNA Expression by Causing Mitochondrial ROS Accumulation, Biogenesis, and Dynamics Disorders.

Acrylamide, a well-documented neurotoxicant, is commonly found as a byproduct of the Maillard reaction in carbohydrate-rich foods. Numerous studies have indicated that acrylamide-induced apoptosis accompanied by mitochondrial dysfunction contributes to its neurotoxicity. However, the mechanisms of how acrylamide causes mitochondrial impairment is not well understood. In this study, we observed destroyed redox balance, accumulated mitochondrial reactive oxygen species (ROS), damaged mitochondrial structures, and activated apoptosis in astrocytes following acrylamide treatment. Furthermore, acrylamide decreased the expression of mitochondrial biogenesis- and dynamics-related genes, including PGC-1α, TFAM, Mfn2, and Opa1, and altered the expression of mitochondrial DNA (mtDNA)-encoded mitochondrial respiratory chain complexes, along with the inhibited mitochondrial respiration. Pretreatment with a mitochondrial ROS scavenger mitoquinone dramatically restored the expressions of PGC-1α, TFAM, Mfn2, and Opa1; protected the mitochondrial structure; and decreased acrylamide-induced apoptosis. Further in vivo experiments confirmed that acrylamide decreased the expressions of PGC-1α, TFAM, Mfn2, and Opa1 in rat brain tissues. These results revealed that acrylamide triggered the mitochondrial ROS accumulation to interfere with mitochondrial biogenesis and dynamics, causing mtDNA damage and finally resulting in mitochondrial dysfunction and apoptosis.

Recent trends and advances in the epidemiology, synergism, and delivery system of lycopene as an anti-cancer agent.

Dietary interventions are key nutritional strategies to prevent, improve, and prolong the survival of cancer patients. Lycopene, one of the strongest natural antioxidants, and its biologically active metabolites, have shown significant potential to prevent a variety of cancers, including prostate, breast, and stomach cancers, making it a promising anti-cancer agent. We review the potential regulatory mechanisms and epidemiological evidences of lycopene and its metabolites to delay the progression of cancers at different developmental stages. Recent studies have revealed that lycopene and its metabolites mediate multiple molecular mechanisms in cancer treatment such as redox homeostasis, selective anti-proliferation, apoptosis, anti-angiogenesis, tumour microenvironment regulation, and anti-metastasis and anti-invasion. Gut microbes and cholesterol metabolism are also the potential regulation targets of lycopene and its metabolites. As a dietary supplement, the synergistic interaction of lycopene with other drugs and nutrients is highlighted especially due to its binding activity with other nutrients in the diet found central to the fight against cancer. Furthermore, the application of several of novel lycopene delivery carriers are on the rise including nanoemulsions, nanostructured liposomes, and polymer nanoparticles for cancer prevention as discussed in this review with future needed development. Moreover, the synergistic mechanism between lycopene and other nutrients or drugs and novel delivery systems of lycopene should now be deeply investigated to improve its clinical application in cancer intervention in the future.

PD-1 Immune Checkpoint Inhibitor Therapy Malignant Tumor Based on Monotherapy and Combined Treatment Research.

Recently, immunotherapy has become the fourth pillar of cancer treatment in addition to surgery therapy, chemotherapy, and radiation therapy. The inhibitors of programed cell death protein 1 (PD-1) and its ligand PD-L1 are the new stars in immunotherapy, as they can overcome tumor immunosuppression. However, the efficacy of PD-1 inhibitors still needs to be further developed for clinical treatment. Therefore, research into treatment with anti-PD-1 drugs has emerged as a new development field. This review provides novel insights into the role and mechanism of PD-1 combination anti-tumor therapy, thereby promoting its clinical application in anti-tumor immunotherapy.

Structure and function of soil bacterial communities in the monoculture and mixed plantation of Pinus massoniana and Castanopsis hystrix in southern subtropical China.

Establishing monoculture of native broadleaved tree species and mixed coniferous broadleaved plantations is the tendency for forest management in subtropical China. The variations of structure and function of soil bacterial community in monoculture and mixed tree plantations are still not clear. We examined soil bacterial community structure and function under different soil layers (0-20, 20-40 and 40-60 cm) in three planted forests, including broadleaved Castanopsis hystrix, coniferous Pinus massoniana and their mixed plantation, in south subtropical China, using 16S rRNA gene high-throughput sequencing and PICRUSt prediction. The results showed that soil bacterial community structure of mixed plantation and P. massoniana plantation were similar but being significant different from that in C. hystrix plantation. The diversity, biological pathways metabolic function, and nitrogen cycling function of soil bacterial community in C. hystrix plantation were lower than those in P. massoniana plantation and mixed plantation. Soil total nitrogen, nitrate nitrogen and C/N were the main factors driving the variations of soil bacterial community structure and function among different forest types. Our results suggested that the mixed plantation of C. hystrix and P. massoniana is better than C. hystrix plantation in this area in terms of soil bacterial community structure and function.

Clinical acupuncture therapy for chronic cholecystitis: A protocol for systematic review and meta-analysis.

ABSTRACT: Chronic cholecystitis is a common chronic disease in clinical practice. The incidence of chronic cholecystitis is gradually increasing due to changes in eating habits and even if acute infections aren't treated in time, it can cause serious complications, continue to plague people's daily life and become an economic burden to society. Currently, the curative effect of chronic cholecystitis under the control of western medicine is still lacking and there are adverse reactions. However, based on current clinical controlled trials acupuncture therapy for chronic cholecystitis has gradually become a complementary treatment. Therefore, this systematic review aims to explore the safety and feasibility of acupuncture therapy in the treatment of chronic cholecystitis. METHODS: We will search the following databases: Medline, PubMed, Cochrane Database of Systematic Reviews, Embase, Chinese Biomedical Literatures Database, China National Knowledge Infrastructure, Wang Fang Database, Chinese Scientific Journal Database from inception to February 2021 without any language restriction. At the same time, relevant literature will be searched manually. The main search terms include: "Acupuncture," "Cholecystitis." Data entry will be completed by 2 researchers separately. After entry, cross-checking will be performed to ensure the authenticity of the information. The main outcome criteria include: including the total effective rate of the patient; the traditional Chinese medicine symptom score of the patient includes: abdominal pain, tenderness in the right upper abdomen, and so on; secondary outcome criteria include: gallbladder contraction function and gallbladder thickness, VAS scores, recurrence rate, adverse reactions; use Cochrane risk bias assessment to evaluate and score the included randomized controlled trial; meta-analysis will be performed using RevMan 5.4.0 software. The heterogeneity test is based on the thresholds of P and I2, In order to use solid or random effects models. RESULTS: This systematic review only evaluates the safety and limitations of acupuncture therapy in the treatment of chronic cholecystitis. We will report the full text in the near future. CONCLUSION: This study will explore the safety and limitations of acupuncture therapy in the treatment of chronic cholecystitis, so that acupuncture therapy will be more widely used clinically. TRIAL REGISTRATION NUMBER: INPLASY202120020.