Clinicopathological, molecular, and prognostic features of colorectal carcinomas with KRAS c.34G>T (p.G12C) mutation.

Evidence indicates that combinations of anti-EGFR antibodies and KRAS p.G12C (c.34G>T) inhibitors can be an effective treatment strategy for advanced colorectal cancer. We hypothesized that KRAS c.34G>T (p.G12C)-mutated colorectal carcinoma might be a distinct tumor subtype. We utilized a prospective cohort incident tumor biobank (including 1347 colorectal carcinomas) and detected KRAS c.34G>T (p.G12C) mutation in 43 cases (3.2%) and other KRAS mutations (in codon 12, 13, 61, or 146) in 467 cases (35%). The CpG island methylator phenotype (CIMP)-low prevalence was similarly higher in KRAS c.34G>T mutants (52%) and other KRAS mutants (49%) than in KRAS-wild-type tumors (31%). KRAS c.34G>T mutants showed higher CIMP-high prevalence (14%) and lower CIMP-negative prevalence (33%) compared with other KRAS mutants (6% and 45%, respectively; p = 0.0036). Similar to other KRAS mutants, KRAS c.34G>T-mutated tumors were associated with cecal location, non-microsatellite instability (MSI)-high status, BRAF wild type, and PIK3CA mutation when compared with KRAS-wild-type tumors. Compared with BRAF-mutated tumors, KRAS c.34G>T mutants showed more frequent LINE-1 hypomethylation, a biomarker for early-onset colorectal carcinoma. KRAS c.34G>T mutants were not associated with other features, including the tumor tissue abundance of Fusobacterium nucleatum (F. animalis), pks+ Escherichia coli, Bifidobacterium, or (enterotoxigenic) Bacteroides fragilis. Among 1122 BRAF-wild-type colorectal carcinomas, compared with KRAS-wild-type tumors, multivariable-adjusted colorectal cancer-specific mortality hazard ratios (95% confidence interval) were 1.82 (1.05-3.17) in KRAS c.34G>T (p.G12C)-mutated tumors (p = 0.035) and 1.57 (1.22-2.02) in other KRAS-mutated tumors (p = 0.0004). Our study provides novel evidence for clinical and tumor characteristics of KRAS c.34G>T (p.G12C)-mutated colorectal carcinoma.

Ca2+-nano starch-lutein endowed 3D printed surimi with antioxidation and mutual reinforcing transmembrane transport mechanisms via hepg2 and caco-2 cells model.

To better enhance printing effects meanwhile casting functionality, antioxidation and absorption of bioactive component in printed Ca2+-nano starch (NS)-lutein (L)-surimi were investigated. Results shown that Ca2+-NS-L promoted surimi printability due to enhanced gel strength and denser structure. Mixing Ca2+-NS-L endowed printed surimi with antioxidation (DPPH, ABTS, hydroxyl radical, Fe2+ reduction were 42 %, 79 %, 65 %, 0.104 mg·mL-1, respectively) due to the ability of lutein with more -OH groups and conjugate bonds to capture free radicals. It also manifested in cellular antioxidation that Ca2+-NS-L-surimi regulated the level of Nrf2 to protect gene expression of antioxidases (SOD, CAT, GSH-Px increased by 30-180 %, compared to damaged cells) through keap1-Nrf2-ARE pathway. Additionally, lutein absorption and transportation of Ca2+-NS-L-surimi increased by 20 %, compared to NS-L. Possibly, combination of samples and membrane was facilitated by surface hydrophobic, promoting endocytosis. Meanwhile, digestive surimi (peptides) with acidic-alkaline amino acids and negative charges made samples be attracted and moved in bypass parts under electrostatic traction and repulsion (electrostatic domain) to promote transport process. Also, Ca2+ facilitated CaM expression in membrane and formed Ca2+ channel by combining with CaM to accelerate entry of samples into cells. Conclusively, Ca2+-NS-L both strengthened printability of surimi and antioxidation, promoting application of printed functional surimi.

Superior sodiophilicity and molecule crowding of crown ether boost the electrochemical performance of all-climate sodium-ion batteries.

Sodium-ion batteries (SIBs) as one of the promising alternatives to lithium-ion batteries have achieved remarkable progress in the past. However, the all-climate performance is still very challenging for SIBs. Herein, 15-Crown-5 (15-C-5) is screened as an electrolyte additive from a number of ether molecules theoretically. The good sodiophilicity, high molecule rigidity, and bulky size enable it to reshape the solvation sheath and promote the anion engagement in the solvated structures by molecule crowding. This change also enhances Na-ion transfer, inhibits side reactions, and leads to a thin and robust solid-electrolyte interphase. Furthermore, the electrochemical stability and operating temperature windows of the electrolyte are extended. These profits improve the electrochemical performance of SIBs in all climates, much better than the case without 15-C-5. This improvement is also adopted to µ-Sn, µ-Bi, hard carbon, and MoS2. This work opens a door to prioritize the potential molecules in theory for advanced electrolytes.

Increased serum interleukin-41 correlates with disease severity in myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease mediated by pathogenic antibodies produced by abnormally activated B cells, resulting in neuromuscular junction transmission dysfunction. Interleukin-41 (IL-41) is a novel immunomodulatory cytokine that has been implicated in various metabolic, inflammatory, and autoimmune diseases. The role of IL-41 in MG is still unclear up to now, our study aimed to investigate the level of IL-41 in MG patients and its correlation with clinical features and inflammatory indicators. METHODS: Totally, 60 MG patients and 30 healthy controls (HC) were recruited. Baseline data and laboratory parameters were routinely recorded through electronic medical systems. IL-41 levels were measured by enzyme-linked immunosorbent assay. Proportions of T-cell and B-cell subsets and natural killer cells were analyzed by flow cytometry. The correlation between serum IL-41 and MG related parameters was investigated, and the clinical value of IL-41 in the diagnosis of MG was evaluated by receiver operator characteristic curve (ROC) analysis. RESULTS: Serum IL-41 levels in MG patients were higher than in HC, and were higher in Myasthenia Gravis Foundation of America (MGFA) III + IV group than that in MGFA I + II group. Serum IL-41 was positively correlated with MG-specific activities of daily living scale (MG-ADL), MGFA classification, platelet to lymphocyte ratio (PLR), and proportion of CD19+ B cells, while it was negatively correlated with high-sensitive C-reactive protein (hs-CRP) and circulatory plasma cells in MG patients. Serum IL-41 levels increased in patients who were treated with efgartigimod during the first cycle of therapy. However, compared to disease initiation, serum IL-41 levels decreased when clinical features steadily improved. ROC analysis showed that IL-41 had a diagnostic value for MG. CONCLUSION: The present findings suggested that serum IL-41 was increased in MG patients and was positively associated with the severity of the disease. IL-41 may be essential to the immunopathological mechanism of MG and a potential biomarker for MG.

Discrimination of three commercial tuna species through species-specific peptides: From high-resolution mass spectrometry discovery to MRM validation.

The risk of tuna adulteration is high driven by economic benefits. The authenticity of tuna is required to protect both consumers and tuna stocks. Given this, the study is designed to identify species-specific peptides for distinguishing three commercial tropical tuna species. The peptides derived from trypsin digestion were separated and detected using ultrahigh-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF/MS) in data-dependent acquisition (DDA) mode. Venn analysis showed that there were differences in peptide composition among the three tested tuna species. The biological specificity screening through the National Center for Biotechnology Information's Basic Local Alignment Search Tool (NCBI BLAST) revealed that 93 peptides could serve as potential species-specific peptides. Finally, the detection specificity of species-specific peptides of raw meats and processed products was carried out by multiple reaction monitoring (MRM) mode based on a Q-Trap mass spectrometer. The results showed that three, one and two peptides of Katsuwonus pelamis, Thunnus obesus and Thunnus albacores, respectively could serve as species-specific peptides.

Primary leptomeningeal melanocytic neoplasms: A clinicopathologic, immunohistochemical, and molecular study of 12 cases.

This study investigated the clinicopathological, immunohistochemical, and molecular features of primary leptomeningeal melanocytic neoplasms (LMNs). Twelve LMN cases were retrospectively reviewed. We performed Fluorescence in-situ hybridization (including a 4-probe FISH assay with CDKN2A and MYC assay) and Next-Generation sequencing analyses on available cases. Histologically, 2 tumours were classified as melanocytomas (MC), 2 as intermediate-grade melanocytomas (IMC), and 8 as leptomeningeal melanomas (LMM). Two rare cases of LMM were associated with large plaque-like blue nevus. One MC case was associated with Ota. Ten cases (83.3%) showed melanocytic cells with benign features diffusely proliferating within the meninges. The Ki-67 in three categories differed (MC 0-1%, IMC 0-3%, LMM 3-10%). 57.1% of LMM cases (4/7) were positive for FISH. Nine of 10 tumours harboured activating hotspot mutations in GNAQ, GNA11, or PLCB4. Additional mutations of EIF1AX, SF3B1, or BAP1 were found in 40%, 30%, and 10% of tumours, respectively. During the follow-up (median = 43 months), 5 LMM patients experienced recurrence and/or metastasis, 3 of them died of the disease and the other 2 are alive with the tumour. Our study is by far the first cohort of LMN cases tested by FISH. In addition to morphological indicators including necrosis and mitotic figures, using a combination of Ki-67 and FISH helps to differentiate between IMC and LMM, especially in LMM cases with less pleomorphic features. SF3B1 mutation is first described in 2 cases of plaque-type blue nevus associated with LMM. Patients with SF3B1 mutation might be related to poor prognosis in LMN.

The luxS deletion reduces the spoilage ability of Shewanella putrefaciens: An analysis focusing on quorum sensing and activated methyl cycle.

The luxS mutant strains of Shewanella putrefaciens (SHP) were constructed to investigate the regulations of gene luxS in spoilage ability. The potential regulations of AI-2 quorum sensing (QS) system and activated methyl cycle (AMC) were studied by analyzing the supplementation roles of key circulating substances mediated via luxS, including S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), methionine (Met), homocysteine (Hcy) and 4,5-dihydroxy-2,3-pentanedione (DPD). Growth experiments revealed that the luxS deletion led to certain growth limitations of SHP, which were associated with culture medium and exogenous additives. Meanwhile, the decreased biofilm formation and diminished hydrogen sulfide (H2S) production capacity of SHP were observed after luxS deletion. The relatively lower total volatile base nitrogen (TVB-N) contents and higher sensory scores of fish homogenate with luxS mutant strain inoculation also indicated the weaker spoilage-inducing effects after luxS deletion. However, these deficiencies could be offset with the exogenous supply of circulating substances mentioned above. Our findings suggested that the luxS deletion would reduce the spoilage ability of SHP, which was potentially attributed to the disorder of AMC and AI-2 QS system.

Value of multiple models of diffusion-weighted imaging to predict hepatic lymph node metastases in colorectal liver metastases patients.

BACKGROUND: About 10%-31% of colorectal liver metastases (CRLM) patients would concomitantly show hepatic lymph node metastases (LNM), which was considered as sign of poor biological behavior and a relative contraindication for liver resection. Up to now, there's still lack of reliable preoperative methods to assess the status of hepatic lymph nodes in patients with CRLM, except for pathology examination of lymph node after resection. AIM: To compare the ability of mono-exponential, bi-exponential, and stretched-exponential diffusion-weighted imaging (DWI) models in distinguishing between benign and malignant hepatic lymph nodes in patients with CRLM who received neoadjuvant chemotherapy prior to surgery. METHODS: In this retrospective study, 97 CRLM patients with pathologically confirmed hepatic lymph node status underwent magnetic resonance imaging, including DWI with ten b values before and after chemotherapy. Various parameters, such as the apparent diffusion coefficient from the mono-exponential model, and the true diffusion coefficient, the pseudo-diffusion coefficient, and the perfusion fraction derived from the intravoxel incoherent motion model, along with distributed diffusion coefficient (DDC) and α from the stretched-exponential model (SEM), were measured. The parameters before and after chemotherapy were compared between positive and negative hepatic lymph node groups. A nomogram was constructed to predict the hepatic lymph node status. The reliability and agreement of the measurements were assessed using the coefficient of variation and intraclass correlation coefficient. RESULTS: Multivariate analysis revealed that the pre-treatment DDC value and the short diameter of the largest lymph node after treatment were independent predictors of metastatic hepatic lymph nodes. A nomogram combining these two factors demonstrated excellent performance in distinguishing between benign and malignant lymph nodes in CRLM patients, with an area under the curve of 0.873. Furthermore, parameters from SEM showed substantial repeatability. CONCLUSION: The developed nomogram, incorporating the pre-treatment DDC and the short axis of the largest lymph node, can be used to predict the presence of hepatic LNM in CRLM patients undergoing chemotherapy before surgery. This nomogram was proven to be more valuable, exhibiting superior diagnostic performance compared to quantitative parameters derived from multiple b values of DWI. The nomogram can serve as a preoperative assessment tool for determining the status of hepatic lymph nodes and aiding in the decision-making process for surgical treatment in CRLM patients.

[The Study of Recombinant Interfering Lentiviruses and Overexpressed Adenovirus Vectors Targeting Human c-Cbl Gene： Construction, Identification and Efficacy].

OBJECTIVE: To construct recombinant lentivirus and adenovirus which regulate the expression of c-Cbl gene and evaluate their efficacy. METHODS: The interference lentivirus and overexpressed adenovirus targeting human c-Cbl gene were constructed by gene recombination technology. Quantitative PCR and western blotting were used to detect the expression changes in c-Cbl gene and its transcription after leukemia cells (HL60,THP1) were infected by virus. RESULTS: Three recombinant interfering lentiviral vectors targeting human c-Cbl genes to successfully constructed and were identified by DNA sequencing, and the titers of the packaged viruses were all greater than 1×108 TU/ml. Among them, shRNA-2 lentivirus had the highest interference efficiency, and the expression of c-Cbl gene and CBL protein were decreased about 95% and 60% respectively after leukemia cells were infected with shRNA-2; In addition, the recombinant overexpression adenovirus targeting human c-Cbl gene was packaged successfully with the virus titer greater than 1×109 TU/ml. When leukemia cells were infected with adenovirus, the expression of c-Cbl gene and CBL protein were up-regulated about 10 times and 1.5 times respectively. CONCLUSION: Both recombinant interfering lentivirus and overexpression adenovirus can efficiently infect leukemia cells and affect the expressions of c-Cbl gene and CBL protein. It will lay a preliminary foundation for the subsequent study on the function of c-Cbl gene in tumor cells.

A custom next-generation sequencing panel for 1p/19q codeletion and mutational analysis in gliomas.

The World Health Organization has updated their classification system for the diagnosis of gliomas, combining histological features with molecular data including isocitrate dehydrogenase 1 and codeletion of chromosomal arms 1p and 19q. 1p/19q codeletion analysis is commonly performed by fluorescence in situ hybridization (FISH). In this study, we developed a 57-gene targeted next-generation sequencing (NGS) panel including 1p/19q codeletion detection mainly to assess diagnosis and potential treatment response in melanoma, gastrointestinal stromal tumor, and glioma patients. Loss of heterozygosity analysis was performed using the NGS method on 37 formalin-fixed paraffin-embedded glioma tissues that showed 1p and/or 19q loss determined by FISH. Conventional methods were applied for the validation of some glioma-related gene mutations. In 81.1% (30 of 37) and 94.6% (35 of 37) of cases, 1p and 19q were found to be in agreement whereas concordance for 1p/19q codeletion and no 1p/19q codeletion was found in 94.7% (18 of 19) and 94.4% (17 of 18) of cases, respectively. Overall, comparing NGS results with those of conventional methods showed high concordance. In conclusion, the NGS panel allows reliable analysis of 1p/19q codeletion and mutation at the same time.

VqNAC44 enhances stilbene synthesis and disease resistance in Chinese wild grape by interacting with VqMYB15.

As significant phytoalexins, stilbene compounds can improve the stress resistance of grapes under biotic and abiotic stress conditions and have biological effects such as antitumour, antioxidant, immune regulation and cardiovascular protection activities in humans. RESVERATROL SYNTHASE (RS), also known as STILBENE SYNTHASE (STS), is the critical enzyme regulating stilbene synthesis and has been identified in a few plant species. However, the regulatory mechanisms of stilbene synthesis are uncertain. In this study, an NAC family transcription factor from Vitis quinquangularis, named VqNAC44, was characterized as an indirect regulator of stilbene synthesis. It is worth noting that VqNAC44 did not bind to the STS promoter nor did it interact with the STS protein but interacted with the MYB transcription factor VqMYB15. This interaction between VqMYB15 and VqNAC44 was validated by a yeast two-hybrid assay and bimolecular fluorescence complementation. Overexpressing VqNAC44 in Arabidopsis thaliana significantly increased its tolerance to biotic and abiotic stresses. Transient overexpression of VqNAC44 and VqMYB15 in grape leaves resulted in increased expression of the STS gene and increased production of stilbene compounds. The experimental results confirmed that VqNAC44 regulated stilbene synthesis by interacting with VqMYB15, thereby enhancing the plant stress resistance.

Radiomics analysis from magnetic resonance imaging in predicting the grade of nonfunctioning pancreatic neuroendocrine tumors: a multicenter study.

OBJECTIVES: To explore the potential of radiomics features to predict the histologic grade of nonfunctioning pancreatic neuroendocrine tumor (NF-PNET) patients using non-contrast sequence based on MRI. METHODS: Two hundred twenty-eight patients with NF-PNETs undergoing MRI at 5 centers were retrospectively analyzed. Data from center 1 (n = 115) constituted the training cohort, and data from centers 2-5 (n = 113) constituted the testing cohort. Radiomics features were extracted from T2-weighted images and the apparent diffusion coefficient. The least absolute shrinkage and selection operator was applied to select the most important features and to develop radiomics signatures. The area under receiver operating characteristic curve (AUC) was performed to assess models. RESULTS: Tumor boundary, enhancement homogeneity, and vascular invasion were used to construct the radiological model to stratify NF-PNET patients into grade 1 and 2/3 groups, which yielded AUC of 0.884 and 0.684 in the training and testing groups. A radiomics model including 4 features was constructed, with an AUC of 0.941 and 0.871 in the training and testing cohorts. The fusion model combining the radiomics signature and radiological characteristics showed good performance in the training set (AUC = 0.956) and in the testing set (AUC = 0.864), respectively. CONCLUSION: The developed model that integrates radiomics features with radiological characteristics could be used as a non-invasive, dependable, and accurate tool for the preoperative prediction of grade in NF-PNETs. CLINICAL RELEVANCE STATEMENT: Our study revealed that the fusion model based on a non-contrast MR sequence can be used to predict the histologic grade before operation. The radiomics model may be a new and effective biological marker in NF-PNETs. KEY POINTS: The diagnostic performance of the radiomics model and fusion model was better than that of the model based on clinical information and radiological features in predicting grade 1 and 2/3 of nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs). Good performance of the model in the four external testing cohorts indicated that the radiomics model and fusion model for predicting the grades of NF-PNETs were robust and reliable, indicating the two models could be used in the clinical setting and facilitate the surgeons' decision on risk stratification. The radiomics features were selected from non-contrast T2-weighted images (T2WI) and diffusion-weighted imaging (DWI) sequence, which means that the administration of contrast agent was not needed in grading the NF-PNETs.

MiR-4521 affects the propagation of Cryptosporidium parvum in HCT-8 cells through targeting foxm1 by regulating cell apoptosis.

Cryptosporidium parvum could regulate the expression of microRNAs of epithelial cells to facilitate its intracellular propagation. MiR-4521 has been reported to play an important role during the development and progression of tumors and infectious diseases by regulating cell proliferation, apoptosis, and autophagy. However, the implication of miR-4521 during C. parvum infection was still unknown. In this study, the expression of miR-4521 was found to be upregulated in HCT-8 cells infected with C. parvum from 8 h post-infection (pi) to 48 hpi, and its upregulation would be related with the TLR/NF-κB signal pathway during C. parvum infection. One potential target of miR-4521, foxm1, was down-regulated in HCT-8 cells from 24 hpi to 48 hpi, and the expression of foxm1 was negatively regulated by miR-4521. The target relationship between miR-4521 and foxm1 was further validated by using dual luciferase reporter assay. Further studies showed that miR-4521 promoted the propagation of C. parvum in HCT-8 cells through targeting foxm1 by regulating BCL2-mediating cell apoptosis. These results contribute to further understanding of the regulatory mechanisms of host miRNAs during Cryptosporidium infection.

The impact of indirect notification of a cancer diagnosis and a risk model based on it to predict the prognosis of postoperative stage T3 esophageal cancer patients.

Chinese doctors are required to inform patients' direct relatives of a cancer diagnosis rather than the patients themselves. The disease may be hidden from patients by their family members, which could result in severe outcomes. We selected postoperative T3 esophageal cancer (EsC) patients hospitalized from June 2015 to December 2019 as research subjects. The patients were divided into a direct-notification group and an indirect-notification group. Several variables were used to evaluate both groups' 36-month progress-free survival (PFS). A risk prediction model of prognosis based on the risk score was established, which was assessed using the area under the curve (AUC) of the receiver operating characteristic curve. One hundred and thirteen patients were enrolled in the training group and forty-eight in the validation group. Cox multivariate regression analysis revealed that males, late stage, poor pathological differentiation, and indirect notification were independent worse risk factors for postoperative T3 stage EsC patients at 36-month PFS (hazard ratio (HR) = 0.454, 95% confidence interval (CI): 0.254-0.812, P = .008; HR = 1.560, 95% CI: 1.006-2.420, P = .047; HR = 0.595, 95% CI: 0.378-0.936, P = .025; HR = 2.686, 95% CI: 1.679-4.297, P < 0.001, respectively). The type of notification was the best correlation factor. The risk score was calculated as follows: risk score = 0.988 × cancer notification (indirect = 1, direct = 0)-0.790 × sex (female = 1, Male = 0) + 0.445 × stage (IIIB = 1, IIA + IIB = 0)-0.519 × pathological differentiation (moderately + well = 1, poorly = 0). The model had a sensitivity of 64.8% and specificity of 81.8%, with the AUC at 0.717 (95% CI: 0.614-0.810) in internal verification, and a sensitivity of 56.8% and specificity of 100%, with the AUC at 0.705 (95% CI: 0.651-0.849) in external validation. The model had good internal and external stability. The model showed a Brier score of 0.18. Indirect notification of a cancer diagnosis was an important negative predictor of postoperative EsC patients' PFS. The model displayed good accuracy and stability in the prediction of risk for cancer progression.

Antimicrobial peptide-producing dermal preadipocytes defend against Candida albicans skin infection via the FGFR-MEK-ERK pathway.

Dermal fibroblasts (dFBs) defend against deep bacterial skin infections by differentiating into preadipocytes (pAds) that produce the antimicrobial peptide cathelicidin; this differentiation is known as the dermal reactive adipogenesis response. However, the role of dFBs in fungal infection remains unknown. Here, we found that cathelicidin-producing pAds were present in high numbers in skin lesions from patients with cutaneous Candida granulomas. Second, we showed that dermal Candida albicans (C. albicans) infection in mice robustly triggered the dermal reactive adipogenesis response and induced cathelicidin expression, and inhibition of adipogenesis with pharmacological inhibitors of peroxisome proliferator-activated receptor γ (PPARγ) impaired skin resistance to C. albicans. In vitro, C. albicans products induced cathelicidin expression in pAds, and differentiating pAds markedly suppressed the growth of C. albicans by producing cathelicidin. Finally, we showed that C. albicans induced an antimicrobial response in pAds through the FGFR-MEK-ERK pathway. Together, our data reveal a previously unknown role of dFBs in the defense against skin infection caused by C. albicans.

Association between self-disclosure and benefit finding of Chinese cancer patients caregivers: the mediation effect of coping styles.

PURPOSE: To examine the relationship between self-disclosure, coping styles, and benefit finding (BF) among caregivers of cancer patients. The study also aimed to identify the factors influencing BF and the impact of coping styles on the relationship between self-disclosure and BF. METHODS: Convenience sampling was used to select 300 caregivers of cancer patients aged greater than 18 years from October 2022 to April 2023 in Chengdu, China. The demographic and clinical characteristics questionnaire, the Benefit Finding Scale (BFS), the Distress Disclosure Index Scale (DDI), and the Simple Coping Style Scale (SCSQ) for caregivers were included in this study. Descriptive statistics, t-tests, one-way analysis of variance, Pearson's correlation analyses, and multiple linear regression models were used. The effect of mediation was tested by the PROCESS macro (Model 4) for SPSS 26.0 by Hayes using 5000 bootstrap samples. RESULTS: There were 292 valid questionnaires (effective response rate 97.33%). The total scores of BF, self-disclosure, negative coping style, and positive coping style of caregivers were 67.77 ± 14.78, 38.23 ± 8.59, 19.68 ± 5.98, and 9.88 ± 4.18, respectively; Pearson's correlation analysis showed that BF was positively correlated with self-disclosure, positive coping, and negatively correlated with negative coping; multiple linear regression analysis showed that self-disclosure, positive coping, and negative coping were influential factors of BF. The results revealed that the effect of self-disclosure on BF was partly mediated by coping styles. It also confirmed that the mediation effect accounted for 54.03% of the total effect. CONCLUSION: The BF of caregivers is at a moderate level. Self-disclosure may influence BF partly because of coping styles.

Tumor regression grade combined with post-therapy lymph node status: A novel independent prognostic factor for patients treated with neoadjuvant therapy followed by surgery in locally advanced gastroesophageal junction and gastric carcinoma.

BACKGROUND: Tumor regression grade (TRG) is a measure of histopathological response to neoadjuvant therapy (NAT). Post-therapy lymph node (ypN) metastasis was reported as a prognostic factor. However, the evaluation of the treatment effectiveness of NAT has not been well studied. Here, we explored whether TRG combined with ypN status could be a prognostic factor for gastroesophageal junction (GEJ) and gastric cancer (GC). Besides, we aimed at making clear the association of different neoadjuvant regimens with different TRG and ypN status. METHODS: 376 patients with GEJ or GC accepting NAT in Peking University Cancer Hospital were retrospectively collected from January 1, 2003 to June 30, 2021. According to TRG and ypN status, patients were innovatively categorized into four groups: TRG0N0, TRG1-3N0, TRG0-1N+, and TRG2-3N+. We applied Kaplan-Meier method and log-rank test to testify the differences in disease free survival (DFS) and overall survival (OS) among four groups. Univariate and multivariate analyses were performed to examine the relationships between TRG combined with ypN status and prognosis. RESULTS: We observed significant survival differences among the four groups (p < 0.001, respectively). Median DFS and OS of patients with TRG0N0, TRG1-3N0, and TRG0-1N+ were not reached, whereas these of patients with TRG2-3N+ were 17.37 months (95% CI, 14.14-20.60 months) and 39.97 months (95% CI, 27.05-52.89 months). TRG combined with ypN status was still an independent predictor for both DFS (p < 0.001) and OS (p < 0.001) in multivariate analysis. Chi-squared test showed TRG combined with ypN status was significantly associated with different preoperative treatments (p < 0.001). Patients receiving immunotherapy achieved the highest TRG0N0 rate (31.9%). CONCLUSION: Our results demonstrate that TRG combined with ypN status is a novel independent predictor of both DFS and OS in resectable, locally advanced GEJ and GC. Neoadjuvant immunotherapy achieved the highest TRG0N0 rate.

Hepatic Krüppel-like factor 14 regulates lipid metabolism in nonalcoholic steatohepatitis mice.

Excessive lipid accumulation is a critical characteristic in the development of nonalcoholic steatohepatitis (NASH). The underlying molecular mechanism, however, is unclear. In this study, we explored whether and how Krüppel-like factor 14 (KLF14) affects hepatic lipid metabolism in NASH. KLF14 expression was detected in NASH patients and mice fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Adeno-associated viruses and adenoviruses were used to alter hepatic KLF14 expression in vivo or in vitro to investigate how KLF14 functions in lipid regulation. The molecular mechanisms were explored using RNA-seq, luciferase reporter, and ChIP assays. The fatty liver phenotype was analyzed histopathologically, and serum and hepatocyte biochemical parameters were measured. The NASH mouse model developed quickly in C57BL/6J mice fed a CDAHFD for 8 weeks. We found that KLF14 expression was decreased in NASH patients and CDAHFD mice. Oleic acid and palmitic acid treatment also reduced KLF14 levels in hepatocytes. KLF14 knockdown downregulated the genes involved in fatty acid oxidation, promoting the progression of hepatic steatosis. In contrast, hepatic KLF14 overexpression alleviated lipid accumulation and oxidative stress in CDAHFD mice. These effects resulted from direct activation of the PPARα signaling pathway. PPARα inhibition diminished the KLF14 overexpression-reduced protective effects against steatosis in OA&PA-treated MPHs and AAV-KLF14-infected CDAHFD mice. These data reveal that hepatic KLF14 regulates lipid accumulation and oxidative stress through the KLF14-PPARα pathway as NASH progresses. KLF14 may be a novel therapeutic target for hepatic steatosis.

Ectomycorrhizal fungi, two species of Laccaria, differentially block the migration and accumulation of cadmium and copper in Pinus densiflora.

The root tips of host plant species can establish ectomycorrhizae with their fungal partners, thereby altering the responses of the host plants to heavy metal (HM) toxicity. Here, two species of Laccaria, L. bicolor and L. japonica, were investigated in symbiosis with Pinus densiflora to study their potential for promotion of phytoremediation of HM-contaminated soils in pot experiments. The results showed that L. japonica had significantly higher dry biomass than L. bicolor in mycelia grown on modified Melin-Norkrans medium containing elevated levels of cadmium (Cd) or copper (Cu). Meanwhile, the accumulations of Cd or Cu in L. bicolor mycelia were much higher than that in L. japonica at the same level of Cd or Cu. Therefore, L. japonica displayed a stronger tolerance to HM toxicity than L. bicolor in situ. Compared with non-mycorrhizal P. densiflora seedlings, inoculation with two Laccaria species significantly increased the growth of P. densiflora seedlings in absence or presence of HM. The mantle of host roots blocked the uptake and migration of HM, which led to the decrease of Cd and Cu accumulation in the P. densiflora shoots and roots, except for the root Cd accumulation of L. bicolor-mycorrhizal plants when 25 mg kg-1 Cd exposure. Furthermore, HM distribution in mycelia showed Cd and Cu are mainly retained in the cell walls of mycelia. These results provide strong evidence that the two species of Laccaria in this system may have different strategies to assist host tree against HM toxicity.