DSN-DDI: an accurate and generalized framework for drug-drug interaction prediction by dual-view representation learning.

Drug-drug interaction (DDI) prediction identifies interactions of drug combinations in which the adverse side effects caused by the physicochemical incompatibility have attracted much attention. Previous studies usually model drug information from single or dual views of the whole drug molecules but ignore the detailed interactions among atoms, which leads to incomplete and noisy information and limits the accuracy of DDI prediction. In this work, we propose a novel dual-view drug representation learning network for DDI prediction ('DSN-DDI'), which employs local and global representation learning modules iteratively and learns drug substructures from the single drug ('intra-view') and the drug pair ('inter-view') simultaneously. Comprehensive evaluations demonstrate that DSN-DDI significantly improved performance on DDI prediction for the existing drugs by achieving a relatively improved accuracy of 13.01% and an over 99% accuracy under the transductive setting. More importantly, DSN-DDI achieves a relatively improved accuracy of 7.07% to unseen drugs and shows the usefulness for real-world DDI applications. Finally, DSN-DDI exhibits good transferability on synergistic drug combination prediction and thus can serve as a generalized framework in the drug discovery field.

Rapid pulmonary 129Xe ventilation MRI of discharged COVID-19 patients with zigzag sampling.

PURPOSE: To demonstrate the feasibility of zigzag sampling for 3D rapid hyperpolarized 129Xe ventilation MRI in human. METHODS: Zigzag sampling in one direction was combined with gradient-recalled echo sequence (GRE-zigzag-Y) to acquire hyperpolarized 129Xe ventilation images. Image quality was compared with a balanced SSFP (bSSFP) sequence with the same spatial resolution for 12 healthy volunteers (HVs). For another 8 HVs and 9 discharged coronavirus disease 2019 subjects, isotropic resolution 129Xe ventilation images were acquired using zigzag sampling in two directions through GRE-zigzag-YZ. 129Xe ventilation defect percent (VDP) was quantified for GRE-zigzag-YZ and bSSFP acquisitions. Relationships and agreement between these VDP measurements were evaluated using Pearson correlation coefficient (r) and Bland-Altman analysis. RESULTS: For 12 HVs, GRE-zigzag-Y and bSSFP required 2.2 s and 10.5 s, respectively, to acquire 129Xe images with a spatial resolution of 3.96 × 3.96 × 10.5 mm3. Structural similarity index, mean absolute error, and Dice similarity coefficient between the two sets of images and ventilated lung regions were 0.85 ± 0.03, 0.0015 ± 0.0001, and 0.91 ± 0.02, respectively. For another 8 HVs and 9 coronavirus disease 2019 subjects, 129Xe images with a nominal spatial resolution of 2.5 × 2.5 × 2.5 mm3 were acquired within 5.5 s per subject using GRE-zigzag-YZ. VDP provided by GRE-zigzag-YZ was strongly correlated (R2 = 0.93, p < 0.0001) with that generated by bSSFP with minimal biases (bias = -0.005%, 95% limit-of-agreement = [-0.414%, 0.424%]). CONCLUSION: Zigzag sampling combined with GRE sequence provides a way for rapid 129Xe ventilation imaging.

Perilipin 5 protects the mitochondrial oxidative functions and improves the alcoholic liver injury in mice.

BACKGROUND AND AIMS: Alcohol consumption is a well-established risk factor for the onset and progression of hepatic steatosis. Perilipin 5 (Plin5), a lipid droplet protein, is an important protective factor against hepatic lipotoxicity induced by excessive lipolysis, but its role and molecular mechanism in alcoholic liver disease (ALD) are not fully elucidated. METHODS: The optimized National Institute on Alcohol Abuse and Alcoholism model was used to construct ALD model mice. Automatic biochemical analyser was used for Biochemical Parameters. The primary hepatocytes and Plin5-overexpressed HepG2 cells (including full-length Plin5 and Plin5 deleting 444-464 aa) were used for in vitro experiment. Haematoxylin and Eosin staining, Oil Red O staining, Bodipy 493/503 staining, Periodic Acid-Schiff staining, immunohistochemistry and JC-1 staining were used to evaluate cell morphology, lipids, glycogen, inflammation and membrane potential. Commercially kits are used to detect glycolipid metabolites, such as triglycerides, glycogen, glucose, reactive oxygen species, lactic acids, ketone bodies. Fluorescently labelled deoxyglucose, NBDG, was used for glucose intake. An XF96 extracellular flux analyser was used to determinate oxygen consumption rate in hepatocytes. The morphological and structural damage of mitochondria was evaluated by electron microscopy. Classical ultracentrifugation is used to separate the subcellular organelles of tissues and cells. Immunoblotting and qPCR were used to detect changes in mRNA and protein levels of related genes. RESULTS: Our results showed that the expression of Plin5 in mouse livers was enhanced by alcohol intake, and Plin5 deficiency aggravated the alcohol-induced liver injury. To clarify the mechanism, we found that Plin5 deficiency significantly elevated the hepatic NADH levels and ketone body production in the alcohol-treated mice. As NADH elevation could promote the reduction of pyruvate into lactate and then inhibit the gluconeogenesis, alcohol-treated Plin5-deficient mice exhibited more lactate production and severer hypoglycemia. These results implied that Plin5 deficiency impaired the mitochondrial oxidative functions in the presence of alcohol. In addition, we demonstrated that Plin5 could be recruited onto mitochondria by alcohol, while Plin5 without mitochondrial targeting sequences lost its mitochondrial protection functions. CONCLUSION: Collectively, this study demonstrated that the mitochondrial Plin5 could protect the alcohol-induced mitochondrial injury, which provides an important new insight on the roles of Plin5 in highly oxidative tissues.

Visualizing the Path of DNA through Proteins Using DREEM Imaging.

Many cellular functions require the assembly of multiprotein-DNA complexes. A growing area of structural biology aims to characterize these dynamic structures by combining atomic-resolution crystal structures with lower-resolution data from techniques that provide distributions of species, such as small-angle X-ray scattering, electron microscopy, and atomic force microscopy (AFM). A significant limitation in these combinatorial methods is localization of the DNA within the multiprotein complex. Here, we combine AFM with an electrostatic force microscopy (EFM) method to develop an exquisitely sensitive dual-resonance-frequency-enhanced EFM (DREEM) capable of resolving DNA within protein-DNA complexes. Imaging of nucleosomes and DNA mismatch repair complexes demonstrates that DREEM can reveal both the path of the DNA wrapping around histones and the path of DNA as it passes through both single proteins and multiprotein complexes. Finally, DREEM imaging requires only minor modifications of many existing commercial AFMs, making the technique readily available.

Physical symptoms and anxiety and depression in older patients with advanced cancer in China: a network analysis.

BACKGROUND: Little is understood about the association between psychosomatic symptoms and advanced cancer among older Chinese patients. METHODS: This secondary analysis was part of a multicenter cross-sectional study based on an electronic patient-reported outcome platform. Patients with advanced cancer were included between August 2019 and December 2020 in China. Participants (over 60 years) completed the MD Anderson Symptom Inventory (MDASI) and Hospital Anxiety and Depression Scale (HADS) to measure symptom burden. Network analysis was also conducted to investigate the network structure, centrality indices (strength, closeness, and betweenness) and network stability. RESULTS: A total of 1022 patients with a mean age of 66 (60-88) years were included; 727 (71.1%) were males, and 295 (28.9%) were females. A total of 64.9% of older patients with advanced cancer had one or more symptoms, and up to 80% had anxiety and depression. The generated network indicated that the physical symptoms, anxiety and depression symptom communities were well connected with each other. Based on an evaluation of the centrality indices, 'distress/feeling upset' (MDASI 5) appears to be a structurally important node in all three networks, and 'I lost interest in my own appearance' (HADS-D4) had the lowest centrality indices. The network stability was relatively high (> 0.7). CONCLUSION: The symptom burden remains high in older patients with advanced cancer in China. Psychosomatic symptoms are highly interactive and often present as comorbidities. This network can be used to provide targeted interventions to optimize symptom management in older patients with advanced cancer in China. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1900024957), registered on 06/12/2020.

Genetic Analysis of Stripe Rust Resistance in the Chinese Wheat Cultivar Luomai 163.

Stripe or yellow rust (YR) caused by Puccinia striiformis tritici (Pst) is an important foliar disease affecting wheat production globally. Resistant varieties are the most economically and environmentally effective way to manage this disease. The common winter wheat (Triticum aestivum L.) cultivar Luomai 163 exhibited resistance to Pst races CYR32 and CYR33 at the seedling stage and showed a high level adult plant resistance in the field. To understand the genetic basis of YR resistance in this cultivar, 142 F5 recombinant inbred lines (RILs) derived from cross Apav#1 × LM163 and both parents were genotyped with the 16K SNP array and bulked segregant analysis sequencing (BSA-Seq). The analysis detected a major gene, YrLM163, at the seedling stage associated with the 1BL.1RS translocation. Additionally, three genes for resistance at the adult plant stage were detected on chromosome arms 1BL (Lr46/Yr29/Pm39/Sr58), 6BS and 6BL in Luomai 163, whereas Apav#1 contributed resistance at a QTL on 2BL. These QTL explained YR disease severity variations ranging from 6.9 to 54.8%. KASP markers KASP-2BL, KASP-6BS and KASP-6BL for three novel loci QYr.hzau-2BL, QYr.hzau-6BS and QYr.hzau-6BL were developed and validated. QYr.hzau-1BL, QYr.hzau-2BL and QYr.hzau-6BS showed varying degrees of resistance to YR when present individually or in combination based on genotype and phenotype analysis of a panel of 570 wheat accessions. Six RILs combining resistance alleles of all QTL, showing higher resistance to YR in the field than Luomai 163 with disease severities of 10.7-16.0%, are important germplasm resources for breeding programs to develop YR resistant wheat varieties with good agronomic traits.

High-efficiency Electroreduction of O2 into H2 O2 over ZnCo Bimetallic Triazole Frameworks Promoted by Ligand Activation.

Co-based metal-organic frameworks (MOFs) as electrocatalysts for two-electron oxygen reduction reaction (2e- ORR) are highly promising for H2 O2 production, but suffer from the intrinsic activity-selectivity trade-off. Herein, we report a ZnCo bimetal-triazole framework (ZnCo-MTF) as high-efficiency 2e- ORR electrocatalysts. The experimental and theoretical results demonstrate that the coordination between 1,2,3-triazole and Co increases the antibonding-orbital occupancy on the Co-N bond, promoting the activation of Co center. Besides, the adjacent Zn-Co sites on 1,2,3-triazole enable an asymmetric "side-on" adsorption mode of O2 , favoring the reduction of O2 molecules and desorption of OOH* intermediate. By virtue of the unique ligand effect, the ZnCo-MTF exhibits a 2e- ORR selectivity of ≈100 %, onset potential of 0.614 V and H2 O2 production rate of 5.55 mol gcat -1 h-1 , superior to the state-of-the-art zeolite imidazole frameworks. Our work paves the way for the design of 2e- ORR electrocatalysts with desirable coordination and electronic structure.

Crystal Engineering Enables Cobalt-Based Metal-Organic Frameworks as High-Performance Electrocatalysts for H2O2 Production.

Metal-organic frameworks (MOFs) with highly adjustable structures are an emerging family of electrocatalysts in two-electron oxygen reduction reaction (2e-ORR) for H2O2 production. However, the development of MOF-based 2e-ORR catalysts with high H2O2 selectivity and production rate remains challenging. Herein, an elaborate design with fine control over MOFs at both atomic and nano-scale is demonstrated, enabling the well-known Zn/Co bimetallic zeolite imidazole frameworks (ZnCo-ZIFs) as excellent 2e-ORR electrocatalysts. Experimental results combined with density functional theory simulation have shown that the atomic level control can regulate the role of water molecules participating in the ORR process, and the morphology control over desired facet exposure adjusts the coordination unsaturation degree of active sites. The structural regulation at two length scales leads to synchronous control over both the kinetics and thermodynamics for ORR on bimetallic ZIF catalysts. The optimized ZnCo-ZIF with a Zn/Co molar ratio of 9/1 and predominant {001} facet exposure exhibits a high 2e- selectivity of ∼100% and a H2O2 yield of 4.35 mol gcat-1 h-1. The findings pave a new avenue toward the development of multivariate MOFs as advanced 2e-ORR electrocatalysts.

Neuronal MeCP2 in the dentate gyrus regulates mossy fiber sprouting of mice with temporal lobe epilepsy.

Sprouting of mossy fibers, one of the most consistent findings in tissue from patients with mesial temporal lobe epilepsy, exhibits several uncommon axonal growth features and has been considered a paradigmatic example of circuit plasticity that occurs in the adult brain. Clarifying the mechanisms responsible may provide new insight into epileptogenesis as well as axon misguidance in the central nervous system. Methyl-CpG-binding protein 2 (MeCP2) binds to methylated genomic DNA to regulate a range of physiological functions implicated in neuronal development and adult synaptic plasticity. However, exploring the potential role of MeCP2 in the documented misguidance of axons in the dentate gyrus has not yet been attempted. In this study, a status epilepticus-induced decrease of neuronal MeCP2 was observed in the dentate gyrus (DG). An essential regulatory role of MeCP2 in the development of functional mossy fiber sprouting (MFS) was confirmed through stereotaxic injection of a recombinant adeno-associated virus (AAV) to up- or down-regulate MeCP2 in the dentate neurons. Chromatin immunoprecipitation sequencing (ChIP-seq) was performed to identify the binding profile of native MeCP2 using micro-dissected dentate tissues. In both dentate tissues and HT22 cell lines, we demonstrated that MeCP2 could act as a transcription repressor on miR-682 with the involvement of the DNA methylation mechanism. Further, we found that miR-682 could bind to mRNA of phosphatase and tensin homolog (PTEN) in a sequence specific manner, thus leading to the suppression of PTEN and excessive activation of mTOR. This study therefore presents a novel epigenetic mechanism by identifying MeCP2/miR-682/PTEN/mTOR as an essential signal pathway in regulating the formation of MFS in the temporal lobe epileptic (TLE) mice. SIGNIFICANCE STATEMENT: Understanding the mechanisms that regulate axon guidance is important for a better comprehension of neural disorders. Sprouting of mossy fibers, one of the most consistent findings in patients with mesial temporal lobe epilepsy, has been considered a paradigmatic example of circuit plasticity in the adult brain. Although abnormal regulation of DNA methylation has been observed in both experimental rodents and humans with epilepsy, the potential role of DNA methylation in this well-documented example of sprouting of dentate axon remains elusive. This study demonstrates an essential role of methyl-CpG-binding protein 2 in the formation of mossy fiber sprouting. The underlying signal pathway has been also identified. The data hence provide new insight into epileptogenesis as well as axon misguidance in the central nervous system.

Identification of signature of tumor-infiltrating CD8 T lymphocytes in prognosis and immunotherapy of colon cancer by machine learning.

BACKGROUND: To explore the specific marker of CD8+ T cell subsets which are closely related to the prognosis and immunotherapy of patients with colon cancer. METHODS: 18 kinds of immune cell expression profile data sets were obtained from GEO database. Compared with other immune cell types, the specific markers of CD8 (+) T cells (TI-CD8) in colorectal cancer were screened. Regression analyses were used to further screen prognostic related genes and construct a prognostic evaluation model. The patients were stratified and analyzed according to the risk scores, KRAS mutation status, stage, lymphatic infiltration and other indicators. The landscape of infiltration level, mutation and copy number variation of immune subsets in high and low TI-CD8Sig score groups were compared and analyzed. The difference of drug response between high and low TI-CD8Sig score groups was analyzed. Differential expression of the model genes was verified by the HPA database. RESULTS: Six prognostic-related CD8T cell-specific gene targets were further screened, and the prognostic evaluation model was constructed. The AUC value of the model is >0.75. FAT3 and UNC13C showed a high mutation state in the low-risk group, while USH2A, MUC5B et al. specifically showed a high mutation state in the high-risk group. Compared with the low-risk group, the high-risk group had lower effective rate of drug response. The expression of PD-1 gene was positively correlated with the level of TI-CD8Sig score. CONCLUSION: The risk assessment model based on CD8T cell-specific marker genes can effectively predict the prognosis and the drug response of patients with CRC.

Spatial Specific Janus S-Scheme Photocatalyst with Enhanced H2 O2 Production Performance.

Photocatalytic oxygen reduction reaction (ORR) for H2 O2 production in the absence of sacrificing agents is a green approach and of great significance, where the design of photocatalysts with high performance is the central task. Herein, a spatial specific S-scheme heterojunction design by introducing a novel semiconducting pair with a S-scheme mechanism in a purpose-designed Janus core-shell-structured hollow morphology is reported. In this design, TiO2 nanocrystals are grown inside the inner wall of resorcinol-formaldehyde (RF) resin hollow nanocakes with a reverse bumpy ball morphology (TiO2 @RF). The S-scheme heterojunction preserves the high redox ability of the TiO2 and RF pair, the spatial specific Janus design enhances the charge separation, promotes active site exposure, and reduces the H2 O2 decomposition to a large extent. The TiO2 @RF photocatalyst shows a high H2 O2 yield of 66.6 mM g-1  h-1 and solar-to-chemical conversion efficiency of 1.11%, superior to another Janus structure (RF@TiO2 ) with the same heterojunction but a reversed Janus spatial arrangement, and most reported photocatalysts under similar reaction conditions. The work has paved the way toward the design of next-generation photocatalysts for green synthesis of H2 O2 production.

Multistimuli-Responsive Chromism of Vinylene-Linked Bisflavin Based on the Aggregation and Redox Properties.

Multistimuli-responsive chromism was observed for vinylene-linked bisflavin 1 a with an extended π-conjugated platform. The yellow emission of a dilute solution of 1 a in CHCl3 (0.2 mM) observed at 298 K under UV excitation was changed to orange or red emission upon (1) an increase of concentration, (2) a decrease of temperature, and (3) variation of the solvent. This is in contrast to the almost non stimuli-responsive chromism of the N-methylated bisflavin analogue 1 b and monoflavin 2 a. Mechanistic investigation by 1 H NMR analysis under various conditions revealed that the extended π-conjugation platform and imide moiety of 1 a generate controllability in the formation of lower- and higher-ordered aggregates, which induce variation of the emission color upon change. Bisflavin 1 a also exhibited redox-induced chromism, where the orange emission of 1 a was quenched by the addition of hydrazine under anaerobic conditions, and changed back to the original emission upon subsequent bubbling of O2 gas.

C(sp3)-H Aerobic Alkenylation of Tetrahydroisoquinolines via Organic Electrosynthesis.

A method for the C(sp3)-H alkenylation of N-aryl-tetrahydroisoquinoline (THIQ) has been developed by the combination of electrooxidation and a copper catalyst. The corresponding products were obtained with good to excellent yields under mild conditions. Besides, the addition of TEMPO as an electron mediator is crucial to this transformation, since the oxidative reaction could proceed under a low electrode potential. In addition, the catalytic asymmetric variant has also been demonstrated with good enantioselectivity.

A simple ratiometric fluorescent probe for two-photon imaging of carbon monoxide in living cells and zebrafish.

Carbon monoxide (CO) is an important gas signaling molecule and has been widely involved in regulating important life processes. Effective monitoring of CO in living systems is critical. Combined with the accuracy of ratio detection and the advantages of two-photon imaging, a simple ratiometric two-photon fluorescent probe RTFP was rationally designed and synthesized using 7-(diethylamino)-4-hydroxycoumarin as a two-photon fluorophore and allyl carbonate as the reactive unit. Probe RTFP exhibited excellent selectivity and sensitivity towards CO, and was successfully applied to image endogenous CO in living cells and zebrafish.

Dynamic human MutSα-MutLα complexes compact mismatched DNA.

DNA mismatch repair (MMR) corrects errors that occur during DNA replication. In humans, mutations in the proteins MutSα and MutLα that initiate MMR cause Lynch syndrome, the most common hereditary cancer. MutSα surveilles the DNA, and upon recognition of a replication error it undergoes adenosine triphosphate-dependent conformational changes and recruits MutLα. Subsequently, proliferating cell nuclear antigen (PCNA) activates MutLα to nick the error-containing strand to allow excision and resynthesis. The structure-function properties of these obligate MutSα-MutLα complexes remain mostly unexplored in higher eukaryotes, and models are predominately based on studies of prokaryotic proteins. Here, we utilize atomic force microscopy (AFM) coupled with other methods to reveal time- and concentration-dependent stoichiometries and conformations of assembling human MutSα-MutLα-DNA complexes. We find that they assemble into multimeric complexes comprising three to eight proteins around a mismatch on DNA. On the timescale of a few minutes, these complexes rearrange, folding and compacting the DNA. These observations contrast with dominant models of MMR initiation that envision diffusive MutS-MutL complexes that move away from the mismatch. Our results suggest MutSα localizes MutLα near the mismatch and promotes DNA configurations that could enhance MMR efficiency by facilitating MutLα nicking the DNA at multiple sites around the mismatch. In addition, such complexes may also protect the mismatch region from nucleosome reassembly until repair occurs, and they could potentially remodel adjacent nucleosomes.

Facial Reanimation After Peripheral Facial Nerve Paralysis: A Single-institution Surgical Experience.

Facial nerve trauma occasionally develops during oral and maxillofacial surgery. This study was aimed at enhancing the available knowledge on facial nerve reanimation correlated to surgery and proposing our surgical algorithm. We retrospectively analyzed medical records of patients who underwent facial reanimation surgery at our hospital. The inclusion criterion was surgery for facial reanimation from January 2004 to June 2021. We included 383 eligible patients who underwent facial reanimation surgery. Trauma or maxillofacial neoplasms were noted in 208 of 383 and 164 of 383 cases, respectively. In 238 of 383 cases, nerve branches were likely more vulnerable. Facial nerve anastomosis was performed in 256 patients. Sixty-eight patients received nerve grafts. In 22 patients, distal facial nerve transfer to the masseteric nerve, sublingual nerve, or contralateral facial nerve was performed. Twenty-five patients received static surgery; in most cases, the temporalis fascia flap (20/25) was used. The nerve function outcomes were HB grade I (n=17), Grade Ⅱ (n=108), Grade Ⅲ (n=118), Grade Ⅳ (n=94), and Grade V (n=46). The mean follow-up time was 4.88 ± 3.93 years. Facial paralysis caused by trauma ( P =0.000), branch injury ( P =0.000), and the primary reconstruction of facial nerve ( P =0.000) were predictive of favorable treatment outcomes. Although facial nerve injury caused by trauma was more likely, cases of interference in facial expression could be limited, and so did the injury to branches. Nerve anastomosis was prioritized if a tension-free suture was possible. Maintaining the integrity of the nerve and shortening the duration of mimetic muscular denervation were crucial.

Characteristics and health risks of population exposure to phthalates via the use of face towels.

The production of face towels is growing at an annual rate of about 4% in China, reaching 1.13 million tons by 2021. Phthalates (PAEs) are widely used in textiles, and face towels, as an important household textile, may expose people to PAEs via the skin, further leading to health risks. We collected new face towels and analyzed the distribution characterization of PAEs in them. The changes of PAEs were explored in a face towel use experiment and a simulated laundry experiment. Based on the use of face towels by 24 volunteers, we calculated the estimated daily intake (EDI) and comprehensively assessed the hazard quotient (HQ), hazard index (HI), and dermal cancer risk (DCR) of PAEs exposure in the population. PAEs were present in new face towels at total concentrations of

Microbial volatile organic compounds 2-heptanol and acetoin control Fusarium crown and root rot of tomato.

Some microbial volatile organic compounds (mVOCs) can act as antagonistic weapons against plant pathogens, but little information is available on the contribution of individual mVOC to biocontrol and how they interact with plant pathogens. In this study, the Bacillus subtilis strain N-18 isolated from the rhizosphere of healthy plants grown in areas where Fusarium crown and root rot (FCRR) of tomato occurs could reduce the 30% of the incidence of FCRR. Moreover, the volatile organic compounds (VOCs) produced by N-18 had inhibitory effects on Fusarium oxysporum f. sp. radicis-lycopersici (FORL). The identification of VOCs of N-18 was analyzed by the solid-phase microextraction coupled to gas chromatography-mass spectrometry. Meanwhile, we conducted sensitivity tests with these potential active ingredients and found that the volatile substances acetoin and 2-heptanol can reduce the 41.33% and 35% of the incidence of FCRR in tomato plants. In addition, the potential target protein of acetoin, found in the cheminformatics and bioinformatics database, was F. oxysporum of hypothetical protein AU210_012600 (FUSOX). Molecular docking results further predicted that acetoin interacts with FUSOX protein. These results reveal the VOCs of N-18 and their active ingredients in response to FORL and provide a basis for further research on regulating and controlling FCRR.

Triterpenoids of Rhus chinensis Supressed Colorectal Cancer Progress by Enhancing Antitumor Immunity and CD8 + T Cells Tumor Infiltration.

The absence of CD8+ T cells in the tumor center has become a major obstacle in the immunotherapy of colorectal cancer. Therefore, new therapeutic strategies are urgently needed to promote the accumulation of CD8+ T cells in the tumor center. Previous studies have shown that triterpenoid of Rhus chinensis (TER) is involved in the proliferation and apoptosis of colorectal cancer cells, and can regulate their immune activity, but its mechanism needs to be further elucidated. In this study, the antitumor effect and adaptive immune response of TER on tumor-bearing mice were evaluated and compared with 5-fluorouracil. The results showed that TER could significantly inhibit tumor growth and prolong the survival time of tumor-bearing mice. The In Vivo studies have shown that TER can not only enhance antitumor immunity and promote the accumulation of CD8 + T cells to tumor sites, but also inhibit tumor progression by regulating the expression of PD-1 and PD-L1 and significantly reducing the mortality of mice. Our study demonstrated for the first time that TER has oncolytic effect, and recruited adaptive immune cells to enhance the efficacy of anti-PD-1/PD-L1 in colorectal cancer, which provides a potential therapeutic target for combined immunotherapy of colorectal cancer.

Prevalence of DSM-5 somatic symptom disorder in Chinese patients with breast cancer.

OBJECTIVE: The aims of this study were to explore the frequency of somatic symptom disorder (SSD) and the relationship between SSD and somatic, psychological, and social factors in Chinese patients with breast cancer. METHODS: This multicenter cross-sectional study enrolled 264 patients with breast cancer from three different departments in Beijing. The structured clinical interview for fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (SCID-5) for SSD. Standardized questionnaires and clinical data were used to compare patients with and without SSD. RESULTS: Somatic symptom disorder was diagnosed in 21.6% (57/264) of all enrolled patients. No differences were found between SSD patients and non-SSD patients in terms of sociodemographic characteristics and tumor-specific variables, except radiotherapy. However, patients with SSD reported higher levels of depression, anxiety and cancer-related worry. They also showed a longer duration of symptoms, greater impairment in daily life, more concern over their physical complaints and more doctor visits. In a stepwise binary logistic regression analysis, among others, higher health anxiety (WI-8, Exp(B) = 0.107, p = 0.009) and more doctor visits (OR = -1.841, p < 0.001) showed a significant association with SSD; the model explained 53.7% of the variance. CONCLUSIONS: Similar to other physical diseases, there is a high prevalence of SSD in patients with breast cancer. Somatic symptom disorder patients differ from non-SSD patients by exhibiting higher cancer-related emotional distress and dysfunctional illness perception and behavior. There remain substantial challenges in the diagnosis of SSD in patients with cancer and other medical conditions. CLINICAL TRIAL REGISTRATION: ChiCTR2100051525.