GbyE: an integrated tool for genome widely association study and genome selection based on genetic by environmental interaction.

BACKGROUND: The growth and development of organism were dependent on the effect of genetic, environment, and their interaction. In recent decades, lots of candidate additive genetic markers and genes had been detected by using genome-widely association study (GWAS). However, restricted to computing power and practical tool, the interactive effect of markers and genes were not revealed clearly. And utilization of these interactive markers is difficult in the breeding and prediction, such as genome selection (GS). RESULTS: Through the Power-FDR curve, the GbyE algorithm can detect more significant genetic loci at different levels of genetic correlation and heritability, especially at low heritability levels. The additive effect of GbyE exhibits high significance on certain chromosomes, while the interactive effect detects more significant sites on other chromosomes, which were not detected in the first two parts. In prediction accuracy testing, in most cases of heritability and genetic correlation, the majority of prediction accuracy of GbyE is significantly higher than that of the mean method, regardless of whether the rrBLUP model or BGLR model is used for statistics. The GbyE algorithm improves the prediction accuracy of the three Bayesian models BRR, BayesA, and BayesLASSO using information from genetic by environmental interaction (G × E) and increases the prediction accuracy by 9.4%, 9.1%, and 11%, respectively, relative to the Mean value method. The GbyE algorithm is significantly superior to the mean method in the absence of a single environment, regardless of the combination of heritability and genetic correlation, especially in the case of high genetic correlation and heritability. CONCLUSIONS: Therefore, this study constructed a new genotype design model program (GbyE) for GWAS and GS using Kronecker product. which was able to clearly estimate the additive and interactive effects separately. The results showed that GbyE can provide higher statistical power for the GWAS and more prediction accuracy of the GS models. In addition, GbyE gives varying degrees of improvement of prediction accuracy in three Bayesian models (BRR, BayesA, and BayesCpi). Whatever the phenotype were missed in the single environment or multiple environments, the GbyE also makes better prediction for inference population set. This study helps us understand the interactive relationship between genomic and environment in the complex traits. The GbyE source code is available at the GitHub website ( https://github.com/liu-xinrui/GbyE ).

Recognizing Functional Groups of MES/APG Mixed Surfactants for Enhanced Solubilization toward Benzo[a]pyrene.

Benzo[a]pyrene is difficult to remove from soil due to its high octanol/water partition coefficient. The use of mixed surfactants can increase solubility but with the risk of secondary soil contamination, and the compounding mechanism is still unclear. This study introduced a new approach using environmentally friendly fatty acid methyl ester sulfonate (MES) and alkyl polyglucoside (APG) to solubilize benzo[a]pyrene. The best result was obtained when the ratio of MES/APG was 7:1 under 6 g/L total concentration, with an apparent solubility (Sw) of 8.58 mg/L and a molar solubilization ratio (MSR) of 1.31 for benzo[a]pyrene, which is comparable to that of Tween 80 (MSR, 0.95). The mechanism indicates that the hydroxyl groups (-OH) in APG form "O-H···OSO2-" hydrogen bonding with the sulfonic acid group (-SO3-) of MES, which reduces the electrostatic repulsion between MES molecules, thus facilitating the formation of large and stable micelles. Moreover, the strong solubilizing effect on benzo[a]pyrene should be ascribed to the low polarity of ester groups (-COOCH3) in MES. Functional groups capable of forming hydrogen bonds and having low polarity are responsible for the enhanced solubilization of benzo[a]pyrene. This understanding helps choose suitable surfactants for the remediation of PAH-contaminated soils.

Mutation of Disulfide Bond Sites Reduces the Immunoreactivity of Cra a 4 by Changing the Structural Characteristics.

Sarcoplasmic calcium-binding protein (Cra a 4) from Crassostrea angulata belongs to the EF-hand superfamily, and understanding of its structure-allergenicity relationship is still insufficient. In this study, chemical denaturants were used to destroy the structure of Cra a 4, showing that disruption of the structure reduced its IgG-/IgE-binding activity. To explore which critical amino acid site affects the allergenicity of Cra a 4, the mutants were obtained by site-directed mutations in the disulfide bonds site (C97), conformational epitopes (I105, D114), or Ca2+-binding region (D106, D110) and their IgG-/IgE-binding activity was reduced significantly using serological tests. Notably, C97A had the lowest immunoreactivity. In addition, two conformational epitopes of Cra 4 were verified. Meanwhile, the increase of the α-helical content, surface hydrophobicity, and surface electrostatic potential of C97A affected its allergenicity. Overall, the understanding of the structure-allergenicity relationship of Cra a 4 allowed the development of a hypoallergenic mutant.

Linear stability for a free boundary problem modeling the growth of tumor cord with time delay.

This paper was concerned with a free boundary problem modeling the growth of tumor cord with a time delay in cell proliferation, in which the cell location was incorporated, the domain was bounded in $ \mathbb{R}^2 $, and its boundary included two disjoint closed curves, one fixed and the other moving and a priori unknown. A parameter $ \mu $ represents the aggressiveness of the tumor. We proved that there exists a unique radially symmetric stationary solution for sufficiently small time delay, and this stationary solution is linearly stable under the nonradially symmetric perturbations for any $ \mu > 0 $. Moreover, adding the time delay in the model leads to a larger stationary tumor. If the tumor aggressiveness parameter is bigger, the time delay has a greater effect on the size of the stationary tumor, but it has no effect on the stability of the stationary solution.

Systems genetics of influenza A virus-infected mice identifies TRIM21 as a critical regulator of pulmonary innate immune response.

Tripartite motif 21 (TRIM21) is a cytosolic Fc receptor that targets antibody-bound, internalized pathogens for destruction. Apart from this intrinsic defense role, TRIM21 is implicated in autoimmune diseases, inflammation, and autophagy. Whether TRIM21 participates in host interactions with influenza A virus (IAV), however, is unknown. By computational modeling of body weight and lung transcriptome data from the BXD parents (C57BL/6 J (B6) and DBA/2 J (D2)) and 41 BXD mouse strains challenged by IAV, we reveal that a Trim21-associated gene network modulates the early host responses to IAV infection. Trim21 transcripts were significantly upregulated in infected mice of both B6 and D2 backgrounds. Its expression was significantly higher in infected D2 than in infected B6 early after infection and significantly correlated with body weight loss. We identified significant trans-eQTL on chromosome 14 that regulates Trim21 expression. Nr1d2 and Il3ra were among the strongest candidate genes. Pathway analysis found Trim21 to be involved in inflammation and immunity related pathways, such as inflammation signaling pathways (TNF, IL-17, and NF-κB), viral detection signaling pathways (NOD-like and RIG-I-like), influenza, and other respiratory viral infections. Knockdown of TRIM21 in human lung epithelial A549 cells significantly augmented IAV-induced expression of IFNB1, IFNL1, CCL5, CXCL10, and IFN-stimulated genes including DDX58 and IFIH1, among others. Our data suggest that a TRIM21-associated gene network is involved in several aspects of inflammation and viral detection mechanisms during IAV infection. We identify and validate TRIM21 as a critical regulator of innate immune responses to IAV in human lung epithelial cells.

Biotransformation of Organophosphate Diesters Characterized via In Vitro Metabolism and In Vivo Screening.

Organophosphate diesters (di-OPEs), as additives in industrial applications and/or transformation products of emerging environmental pollutants, such as organophosphate triesters (tri-OPEs), have been found in the environment and biological matrices. The metabolic fate of di-OPEs in biological media is of great significance for tracing the inherent and precursor toxicity variations. This is the first study to investigate the metabolism of a suite of di-OPEs by liver microsomes and to identify any metabolite of metabolizable di-OPEs in in vitro and in vivo samples. Of the 14 di-OPEs, 5 are significantly metabolizable, and their abundant metabolites with hydroxyl, carboxyl, dealkylated, carbonyl, and/or epoxide groups are tentatively identified. More than half of the di-OPEs are detectable in human serum and/or wild fish tissues, and dibenzyl phosphate (DBzP), bis(2,3-dibromopropyl) phosphate (BDBPP), and isopropyl diphenyl phosphate (ip-DPHP) are first reported at a detectable level in humans and wildlife. Using an in vitro assay and a known biotransformation rule-based integrated screening strategy, 2 and 10 suspected metabolite peaks of DEHP are found in human serum and wild fish samples, respectively, and are then identified as phase I and phase II metabolites of DEHP. This study provides a novel insight into fate and persistence of di-OPE and confirms the presence of di-OPE metabolites in humans and wildlife.

The effect of virtual reality technology in exercise and lung functions of patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a serious chronic disease worldwide, with significant negative impacts on the quality of life, family economic burden, and social healthcare burden of patients. AIMS: The aim of this study was to explore the effects of virtual reality technology on exercise function and lung function in COPD patients. METHODS: A meta-analysis of randomized controlled trials was utilized. PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, Medline, Scopus, China National Knowledge Infrastructure (CNKI), Wanfang Database, Weipu Database (VIP), and Chinese Biomedical Database (CBM) were systematically searched. We included randomized controlled trials published from the establishment of the database to August 10, 2022, on virtual reality technology in COPD patients. Literature retrieval and screening was carried out independently by two reviewers to obtain literature that met our inclusion and exclusion criteria and to extract relevant data. Two reviewers assessed the risk of bias in the included literature. A meta-analysis was performed using Revman 5.4 Software. RESULTS: A total of 10 randomized controlled trials with 539 participants were included. The results showed that virtual reality technology significantly improved the lung function of COPD patients, such as forced expiratory volume (FEV1; MD = 7.29, 95% CI [4.34, 10.24], p < .01) and forced expiratory volume/forced vital capacity (FEV1/FVC; MD = 6.71, 95% CI [4.72, 8.71], p < .01). The combined intervention with different virtual reality technology had different effects on motor function. Compared with endurance training (ET) alone, virtual reality technology combined with ET had no significant effect on the 6-minute walk test (6WMT) in COPD patients (p > .05). Compared with pulmonary rehabilitation (PR) alone, virtual reality technology combined with PR was more effective in increasing 6WMT in COPD patients (MD = 30.80, 95% CI [10.85, 50.74], p < .01). LINKING EVIDENCE TO ACTION: Virtual reality technology can help to improve lung function in COPD patients, and virtual reality combined with PR can improve exercise tolerance in COPD patients. However, due to the limited number of included studies, large-sample, multicenter, high-quality randomized controlled trial studies are needed to provide clear evidence.

Whole-genome resequencing of major populations revealed domestication-related genes in yaks.

BACKGROUND: The yak is a symbol of the Qinghai-Tibet Plateau and provides important basic resources for human life on the plateau. Domestic yaks have been subjected to strong artificial selection and environmental pressures over the long-term. Understanding the molecular mechanisms of phenotypic differences in yak populations can reveal key functional genes involved in the domestication process and improve genetic breeding. MATERIAL AND METHOD: Here, we re-sequenced 80 yaks (Maiwa, Yushu, and Huanhu populations) to identify single-nucleotide polymorphisms (SNPs) as genetic variants. After filtering and quality control, remaining SNPs were kept to identify the genome-wide regions of selective sweeps associated with domestic traits. The four methods (π, XPEHH, iHS, and XP-nSL) were used to detect the population genetic separation. RESULTS: By comparing the differences in the population stratification, linkage disequilibrium decay rate, and characteristic selective sweep signals, we identified 203 putative selective regions of domestic traits, 45 of which were mapped to 27 known genes. They were clustered into 4 major GO biological process terms. All known genes were associated with seven major domestication traits, such as dwarfism (ANKRD28), milk (HECW1, HECW2, and OSBPL2), meat (SPATA5 and GRHL2), fertility (BTBD11 and ARFIP1), adaptation (NCKAP5, ANTXR1, LAMA5, OSBPL2, AOC2, and RYR2), growth (GRHL2, GRID2, SMARCAL1, and EPHB2), and the immune system (INPP5D and ADCYAP1R1). CONCLUSIONS: We provided there is an obvious genetic different among domestic progress in these three yak populations. Our findings improve the understanding of the major genetic switches and domestic processes among yak populations.

High-Density Energetic Materials with Low Mechanical Sensitivity and Twinning Derived from Nitroimidazole Fused Ring.

The innovative synthesis of 3,8-dibromo-2,9-dinitro-5,6-dihydrodiimidazo [1,2-a:2',1'-c]pyrazine and 3,9-dibromo-2,10-dinitro-6,7-dihydro-5H-diimidazo [1,2-a:2',1'-c][1,4]diazepine is described in this study. The tricyclic fused molecular structures are formed by the respective amalgamation of piperazine and homopiperazine with the imidazole ring containing nitro. Compound 1 and 2 possess excellent high-density physical properties (ρ1 = 2.49 g/cm3, ρ2 = 2.35 g/cm3) due to the presence of a fused ring structure and Br atom. In addition to their high density, they have high decomposition temperatures (Td > 290 °C) which means that they have excellent thermal stability and can be used as potential heat-resistant explosives. Low mechanical sensitivities (IS > 40 J, FS > 360 N) are observed. The twinning structure of 2 was resolved by X-ray diffraction. Non-covalent interaction analysis, Hirshfeld surfaces, 2D fingerprint plot, and Electrostatic potential analysis were used to understand the intramolecular interactions in relation to physicochemical properties. The unique structures of this type of compound provide new potential for the evolution of energetic materials.

Object geometry serves humans' intuitive physics of stability.

How do humans judge physical stability? A prevalent account emphasizes the mental simulation of physical events implemented by an intuitive physics engine in the mind. Here we test the extent to which the perceptual features of object geometry are sufficient for supporting judgments of falling direction. In all experiments, adults and children judged the falling direction of a tilted object and, across experiments, objects differed in the geometric features (i.e., geometric centroid, object height, base size and/or aspect ratio) relevant to the judgment. Participants' performance was compared to computational models trained on geometric features, as well as a deep convolutional neural network (ResNet-50), none of which incorporated mental simulation. Adult and child participants' performance was well fit by models of object geometry, particularly the geometric centroid. ResNet-50 also provided a good account of human performance. Altogether, our findings suggest that object geometry may be sufficient for judging the falling direction of tilted objects, independent of mental simulation.

Prevalence of metabolic syndrome in patients with end-stage renal disease: a systematic review and meta-analysis.

BACKGROUND: Metabolic syndrome, a significant risk factor for cardiovascular mortality in patients with end-stage renal disease, profoundly impacts patient prognosis and survival. Despite its clinical importance, the prevalence of metabolic syndrome remains unexplored in this population. Therefore, the objective of this study was to systematically assess the prevalence of metabolic syndrome among patients with end-stage renal disease and raise awareness among healthcare professionals. METHODS: We conducted a comprehensive search in CNKI, WANFANG, WeiPu, CBM, PubMed, Web of Science, EMBASE, and The Cochrane Library databases. The search time was until August 21, 2023. Standardized tables were employed for data extraction and imported into Stata 16.0 software for subsequent meta-analysis. A random-effects model was employed to estimate combined prevalence and 95% confidence intervals. Subgroup and sensitivity analyses were conducted to explore potential sources of heterogeneity, while publication bias was evaluated using a funnel plot and Egger's test. This study has been registered with PROSPERO under the registration number CRD42023456284. RESULTS: This meta-analysis comprised 35 studies involving a total of 14,202 participants. The pooled prevalence estimate for metabolic syndrome was 49.0% [95% CI (46.0,53.0)]. We conducted subgroup analyses based on participant characteristics, gender distribution, publication year, national economic status, diagnostic criteria employed, and components of metabolic syndrome. CONCLUSIONS: The prevalence of metabolic syndrome is higher among patients with end-stage renal disease, necessitating early prevention and control measures to reduce its incidence and delay the progression of the disease, thereby improving patient life expectancy.

Mucinous Cystadenocarcinoma of the Breast with Bone Metastases: First Case Report and Literature Review.

INTRODUCTION: Mucinous cystadenocarcinoma (MCA) of the breast is an extremely rare type of breast carcinoma. Since its biological characteristics, treatment options, and clinical outcomes are unclear, there is a lack of consensus regarding the optimal management of this disease. Thus, our single case report will aid our understanding of its natural history, prognostic factors, and treatment strategies. CASE PRESENTATION: We presented a 54-year-old woman with a case of advanced MCA of the breast accompanied by a huge breast mass, lymph node involvement, and distant bone metastases. We diagnosed primary breast MCA through clinical examination, imaging, and immunohistochemical assessments. Subsequently, the patient was treated with a regimen of nab-paclitaxel and bevacizumab, resulting in a significant clinical response. Progression-free survival was maintained during the 6-month follow-up period. CONCLUSION: We present the first report worldwide of a rare case of MCA of the breast with a large local mass and bone metastases. Our report adds to the limited literature on this rare breast cancer subtype and highlights the importance of accurate diagnosis and appropriate management of aggressive breast tumors.

Prevalence of restless legs syndrome in maintenance hemodialysis patients: A systematic review and meta-analysis.

BACKGROUND: Restless legs syndrome is associated with quality of life and risk of death in maintenance hemodialysis patients. Although relevant meta-analyses have been conducted, epidemiological studies of restless legs syndrome have increased in recent years. OBJECTIVE: Our aim was to systematically assess the prevalence of restless legs syndrome in maintenance hemodialysis patients and to evaluate the effect of different geographic regions, genders, study designs, and years of publication on the prevalence of restless legs syndrome. METHODS: PubMed, Web of Science, EMBASE, The Cochrane Library, China Knowledge Resource Integrated Database, Wanfang Database, Weipu, and Chinese Biomedical Database were searched before March 16, 2023 for the published literature. Two investigators independently performed literature screening, data extraction for eligible studies, and risk of bias assessment. A random-effects model using the stata 15.0 software was used to assess the pooled prevalence of restless legs syndrome. RESULTS: Fifty-seven articles were included in this meta-analysis, and the pooled prevalence of restless legs syndrome in 12,573 maintenance hemodialysis patients was 24.0 % (95 % CI: 21.0%-26.0 %). Maintenance hemodialysis patients from the Americas region and females had severe symptoms of restless legs syndrome, and the prevalence of restless legs syndrome increased from year to year. The prevalence of restless legs syndrome was higher in maintenance hemodialysis patients in cross-sectional studies and cohort studies compared to case-control studies. CONCLUSIONS: Maintenance hemodialysis patients have a significantly higher prevalence of restless legs syndrome. These findings may provide some reference value for hospital nursing staff to focus on the management and treatment of restless legs syndrome in maintenance hemodialysis patients.

A frameshift mutation in the SCNN1B gene in a family with Liddle syndrome: A case report and systematic review.

Liddle syndrome is an autosomal dominant form of monogenic hypertension that is caused by mutations in SCNN1A, SCNN1B or SCNN1G, which respectively encode the α, ß and γ subunits of the epithelial sodium channel. In the present study, DNA was extracted from leukocytes in peripheral blood obtained from all members of a family with Liddle syndrome. Whole­exome sequencing and Sanger sequencing were performed to assess the candidate variant and a co­segregation analysis was conducted. A frameshift mutation in SCNN1B (NM_ 000336: c.1806dupG, p.Pro603Alafs*5) in the family was identified, characterized by early­onset hypertension and hypokalemia. The mutation led to the truncation of the ß subunit of the epithelial sodium channel and a lack of the conservative PY motif. Furthermore, a systematic review of follow­up data from patients with Liddle syndrome with SCNN1B mutations was performed. The follow­up data of 108 patients with pathogenic SCNN1B mutations from 47 families were summarized. Phenotypic heterogeneity was evident in patients with Liddle syndrome and early­onset hypertension was the most frequent symptom. Patients responded well to targeted amiloride therapy with significant improvements in blood pressure and serum potassium concentration. The present study demonstrates that confirmatory genetic testing and targeted therapy can prevent premature onset of clinical endpoint events in patients with Liddle syndrome.

Influencing factors of falls among older adults in Chinese retirement institutions: A systematic review and meta-analysis.

BACKGROUND: The incidence of falling has always been high among the elderly, and it was easy to cause injuries to the elderly and seriously affect their quality of life. There were many studies have been conducted on risk factors affecting the fall of the elderly, but the results widely, retirement institutions as a gathering place for the elderly, there was currently no comprehensive analysis of the factors related to elderly falls in pension institutions. This study aimed to explore the influencing factors of falls among older adults in Chinese nursing homes. METHODS: Chinese and English databases were searched for literature published from database inception to 5 April 2023 on the influencing factors of falls among older adults in Chinese nursing homes. Two reviewers independently screened articles, extracted data, and assessed the quality of the included studies. Meta-analysis was performed using RevMan 5.4 software. RESULTS: Eleven studies involving 3503 participants were included in the meta-analysis. The pooled estimate of falls among older adults in Chinese nursing homes was 32% [95% confidence interval (95%CI) (24.0%, 39.0%)]. The main influencing factors for falls among older adults in Chinese nursing homes were age (Odds Ratio (OR) = 1.53), gender (OR = 5.50), visual impairment (OR = 2.30), sedative-hypnotics (OR = 2.36), fear of falling (OR = 2.95), hypertension (OR = 3.72), static balance (OR = 2.02), three or more chronic diseases (OR = 5.63), cognitive status (OR = 2.64), walking aid use (OR = 1.98), fall-related chronic diseases (OR = 2.48), self-awareness of abilities (OR = 2.43), and frequent reminders for fall prevention (OR = 0.10). CONCLUSION: Falls among older adults in Chinese nursing homes were common, and there were many influencing factors. Timely screening and intervention should be implemented to reduce the adverse consequences of falls on older adults. TRIAL REGISTRATION: Registration number: CRD42023421099.

Identification of Triazolo-quinazolinone Derivatives as Novel and Potent Chitinase OfChi-h Inhibitors Based on Structure-Based Virtual Screening.

Insect chitinase, OfChi-h, from Ostrinia furnacalis, is considered as a promising target for the development of green pesticides. On the basis of the crystal structure of OfChi-h, we successfully obtained a triazolo-quinazolinone scaffold as the novel class of OfChi-h inhibitor via a structure-based virtual screening approach. Rational compound screening enabled us to acquire a potent OfChi-h inhibitor TQ19 with a Ki value of 0.33 µM. Furthermore, the in vivo biological activity of target compounds was assayed. The results showed that compounds TQ8 and TQ19 could dramatically inhibit the growth and development of Ostrinia nubilalis larvae, and most of the compounds showed higher insecticidal activity than hexaflumuron. This present work reveals that triazolo-quinazolinone derivatives can serve as novel candidates for insect growth regulators.

Prevalence of alexithymia in cancer patients: a systematic review and meta-analysis.

PURPOSE: To systematically evaluate the prevalence of alexithymia in cancer patients and to compare the prevalence of alexithymia in different countries, genders, and cancer types. METHODS: We thoroughly searched PubMed, EMBASE, Web of Science, The Cochrane Library, CINAHL, PsychINFO, China Integrated Knowledge Resource Database, Wanfang Database, Weipu Database, and Chinese Biomedical Database for studies on the prevalence of alexithymia in cancer patients from the inception to April 2, 2023. Based on the Stata 15.0 software package, the prevalence of alexithymia in cancer patients was estimated using a random-effects model in this meta-analysis. RESULTS: Eighteen studies with a total of 3,196 participants met the eligibility criteria for the meta-analysis. In 18 studies, 37.0% (95% CI: 28.0% - 46.0%) of cancer patients had alexithymia. 13 studies identified that the pooled mean score of alexithymia in cancer patients was 56.91 (95% CI: 54.44% to 59.37%). The prevalence of alexithymia was higher in cancer patients in developing countries (39.7%, 95% CI: 28.7% to 50.7%), males (40.0%, 95% CI: 24.0% to 55.9%), and colorectal cancer patients (47.3%, 95% CI: 21.3% to 93.3%). CONCLUSIONS: Our study found that the pooled prevalence of alexithymia in cancer patients was 37.0%, and higher in developing countries, males, and patients with colorectal cancer. Understanding the current status of alexithymia in cancer patients, timely identification and treatment by medical practitioners can improve the prognosis of cancer patients. CLINICAL TRIAL REGISTRATION: The protocol was registered in PROSPERO [CRD42023414665].

Curcumin Induces Apoptosis by Suppressing XRCC4 Expression in Hepatocellular Carcinoma.

Curcumin is a chemical with various pharmacological activities used for cancer treatment. It inhibits hepatocellular carcinoma (HCC) by inducing apoptosis. Here, the mechanism underlying the effect of curcumin on the apoptosis of HCC cells was studied. Cell counting kit-8 and plate cloning assays were used to assess the proliferation of HCC cells, and acridine orange/ethidium bromide and Annexin V/PI staining were used to analyze their apoptosis. HCC xenograft tumor models were established to validate anti-cancer effects of curcumin. Expression levels of XRCC4 protein in tumor tissues were assessed by immunohistochemistry. Correlation between XRCC4 expression and the prognosis of patients with HCC was analyzed by integrating publicly available gene expression data. Curcumin inhibited HCC cells proliferation in a dose-dependent manner. Compared with the control group, curcumin significantly promoted the apoptosis of HCC cells in vitro and in vivo. Immunohistochemical analysis revealed that curcumin downregulated XRCC4 expression levels in HCC tissues. Prognosis of HCC patients with high XRCC4 expression was poorer than that of patients with low XRCC4 expression. Therefore, curcumin exerts anti-cancer effects by inhibiting cell proliferation and promoting cell apoptosis in HCC. This may be due to curcumin interference in the repair process of the nonhomologous DNA terminal link of HCC cells by downregulating XRCC4 expression.

Three-Week Versus 4-Week Schedule of nab-Paclitaxel in Patients With Metastatic Breast Cancer: A Randomized Phase II Study.

BACKGROUND: This head-to-head study compared a 3-week versus 4-week schedule of nab-paclitaxel in patients with metastatic breast cancer (mBC). METHODS: Patients with HER2-negative mBC were enrolled and randomly assigned (1:1) to receive nab-paclitaxel for a 3-week schedule (125 mg/m2 on days 1 and 8) or a 4-week schedule (same dose on days 1, 8, and 15) until disease progression or treatment intolerance. Patients with intolerable toxicities were allowed to receive a maintenance regimen after benefiting from nab-paclitaxel. The primary endpoint was progression-free survival (PFS). RESULTS: Ninety-four patients were included in the analysis (n = 47 in each arm). A longer median PFS (mPFS) was observed in the 3-week versus the 4-week schedule in the overall population (not reached vs. 6.8 months; hazard ratio [HR] = 0.44; P = .029). Patients in the 2 arms had a similar overall survival (28.0 vs. 25.8 months), objective response rate (51.1% vs. 48.9%), and disease control rate (93.6% vs. 80.9%). The 3-week schedule was associated with a lower rate of toxicity-related treatment discontinuation (8.5% vs. 29.8%) and dose delays (6.4% vs. 23.4%). CONCLUSION: This study demonstrated the better antitumor activity and safety profile of a 3-week over 4-week nab-paclitaxel schedule in HER2-negative mBC, suggesting that a 3-week schedule may be a better treatment regimen in clinical practice (ClinicalTrials.gov Identifier: NCT04192331).

Iron-chelated semiconducting oligomer nanoparticles for NIR-II fluorescence imaging-guided enhanced chemodynamic/photothermal combination therapy.

Chemodynamic therapy (CDT) has attracted increasing attention owing to its high tumor specificity and low number of side effects. However, the low absolute concentration of reactive oxygen species (ROS) within tumor cells restricts the CDT efficacy. Herein, we use dihydroartemisinin (DHA) to enhance the CDT efficacy and combine photothermal therapy (PTT) to further improve the anticancer effect. To achieve such a goal, an iron-containing semiconducting oligomer nanoparticle (DHA@FePSOD) is prepared by loading DHA into a Fe3+-chelated NIR-II fluorescent semiconducting oligomer (FePSOD). The Fe3+ ion within DHA@FePSOD can be reduced to the Fe2+ ion by glutathione (GSH) and subsequently catalyze the decomposition of hydrogen peroxide (H2O2) into the highly toxic hydroxyl radical (˙OH) for CDT. The loaded DHA may be further reduced by Fe2+ and generate a DHA radical to enhance the CDT efficacy. In addition, DHA@FePSOD shows a good photothermal effect and intense NIR-II fluorescence signal under 808 nm laser irradiation. Both in vitro and in vivo studies prove the better anticancer effect of DHA@FePSOD than FePSOD, which is attributed to the loaded DHA. Furthermore, DHA@FePSOD can effectively accumulate into a tumor and delineate the tumor via NIR-II fluorescence imaging. This study thus provides an efficient approach for developing a NIR-II fluorescence imaging-guided enhanced chemodynamic/photothermal combination therapeutic nanoplatform.