Nitrogen-mediated volatilisation of defensive metabolites in tomato confers resistance to herbivores.

Plants synthesise a vast array of volatile organic compounds (VOCs), which serve as chemical defence and communication agents in their interactions with insect herbivores. Although nitrogen (N) is a critical resource in the production of plant metabolites, its regulatory effects on defensive VOCs remain largely unknown. Here, we investigated the effect of N content in tomato (Solanum lycopersicum) on the tobacco cutworm (Spodoptera litura), a notorious agricultural pest, using biochemical and molecular experiments in combination with insect behavioural and performance analyses. We observed that on tomato leaves with different N contents, S. litura showed distinct feeding preference and growth and developmental performance. Particularly, metabolomics profiling revealed that limited N availability conferred resistance upon tomato plants to S. litura is likely associated with the biosynthesis and emission of the volatile metabolite α-humulene as a repellent. Moreover, exogenous application of α-humulene on tomato leaves elicited a significant repellent response against herbivores. Thus, our findings unravel the key factors involved in N-mediated plant defence against insect herbivores and pave the way for innovation of N management to improve the plant defence responses to facilitate pest control strategies within agroecosystems.

Changes in bacterial community composition in the uterus of Holstein cow with endometritis before and after treatment with oxytetracycline.

It is important to study the bacteria that cause endometritis to identify effective therapeutic drugs for dairy cows. In this study, 20% oxytetracycline was used to treat Holstein cows (n = 6) with severe endometritis. Additional 10 Holstein cows (5 for healthy cows, 5 for cows with mild endometritis) were also selected. At the same time, changes in bacterial communities were monitored by high-throughput sequencing. The results show that Escherichia coli, Staphylococcus aureus and other common pathogenic bacteria could be detected by traditional methods in cows both with and without endometritis. However, 16S sequencing results show that changes in the abundance of these bacteria were not significant. Endometritis is often caused by mixed infections in the uterus. Oxytetracycline did not completely remove existing bacteria. However, oxytetracycline could effectively inhibit endometritis and had a significant inhibitory effect on the genera Bacteroides, Trueperella, Peptoniphilus, Parvimonas, Porphyromonas, and Fusobacterium but had no significant inhibitory effect on the bacterial genera Marinospirillum, Erysipelothrix, and Enteractinococcus. During oxytetracycline treatment, the cell motility, endocrine system, exogenous system, glycan biosynthesis and metabolism, lipid metabolism, metabolism of terpenoids, polyketides, cofactors and vitamins, signal transduction, and transport and catabolism pathways were affected.

Isoprenoid flavonoids isolated from Sophora davidii and their activities induces apoptosis and autophagy in HT29 cells.

Four previously undescribed isoprenoid flavonoids (2-5) were isolated from Sophora davidii, along with five known analogues. The structures of the compounds were established through comprehensive analysis of spectroscopic data, including HRESIMS, 1D and 2D NMR, and absolute configurations determined by theoretical calculations, including ECD and NMR calculation. The cytotoxic effects of the isolated compounds on human HT29 colon cancer cells were evaluated using the MTT assay, compound 1 exhibited cytotoxicity against human HT29 colon cancer cells with an IC50 value of 8.39 ± 0.09 µM. Studies conducted with compound 1 in HT29 cells demonstrated that it may induce apoptosis and autophagy in HT29 by promoting the phosphorylation of P38 MAPK and inhibiting the phosphorylation of Erk MAPK.

Disorganized adrenocortical zonational structure in COVID-19 patients: Implications of critical illness duration.

Aberrant adrenal function has been frequently reported in COVID-19 patients, but histopathological evidence remains limited. This retrospective autopsy study aims to scrutinize the impact of COVID-19 duration on adrenocortical zonational architecture and peripheral corticosteroid reactivity. The adrenal glands procured from 15 long intensive care unit (ICU)-stay COVID-19 patients, 9 short ICU-stay COVID-19 patients, and 20 matched controls. Subjects who had received glucocorticoid treatment prior to sampling were excluded. Applying hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining, we disclosed that the adrenocortical zonational structure was substantially disorganized in COVID-19 patients, which long ICU-stay patients manifested a higher prevalence of severe disorganization (67%) than short ICU-stay patients (11%; P = 0.0058). The adrenal cortex of COVID-19 patients exhibited a 40% decrease in the zona glomerulosa (ZG) area and a 74% increase in the zona fasciculata (ZF) area (both P < 0.0001) relative to controls. Furthermore, among long ICU-stay COVID-19 patients, the ZG area diminished by 31% (P = 0.0004), and the ZF area expanded by 27% (P = 0.0004) in comparison to short ICU-stay patients. The zona reticularis (ZR) area remained unaltered. Nuclear translocation of corticosteroid receptors in the liver and kidney of long ICU-stay COVID-19 patients was at least 43% lower than in short ICU-stay patients (both P < 0.05). These findings underscore the necessity for clinicians to monitor adrenal function in long-stay COVID-19 patients.

Long-Term Outcomes of dMMR/MSI-H Rectal Cancer Treated With Anti-PD-1-Based Immunotherapy as Curative-Intent Treatment.

BACKGROUND: Neoadjuvant anti-PD-1 therapy has shown encouraging efficacy in patients with deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer (LARC), which suggests its potential as a curative-intent therapy and a promising treatment option for organ preservation. We aimed to investigate the long-term outcomes of patients with dMMR/MSI-H LARC who experienced clinical complete response (cCR) after anti-PD-1 therapy. METHODS: We retrospectively analyzed patients with dMMR/MSI-H LARC who achieved cCR and received nonoperative management following neoadjuvant anti-PD-1-based treatment from 4 Chinese medical centers. Patients were followed up for at least 1 year after they achieved cCR, their clinical data were collected, and survival outcomes were analyzed using the Kaplan-Meier method. RESULTS: A total of 24 patients who achieved cCR and received nonoperative management from March 2018 to May 2022 were included, with a median age of 51.0 years (range, 19.0-77.0 years). The median treatment course to reach cCR was 6.0 (range, 1.0-12.0). Fifteen patients (62.5%) continued their treatments after experiencing cCR, and the median treatment course was 17.0 (range, 3.0-36.0). No local regrowth or distant metastasis was observed in a median follow-up time of 29.1 months (range, 12.6-48.5 months) after cCR. The 3-year disease-free and overall survivals were both 100%. CONCLUSIONS: Patients with dMMR/MSI-H locally advanced or low-lying rectal cancer who achieved cCR following anti-PD-1-based therapy had promising long-term outcomes. A prospective clinical trial with a larger sample size is required to further validate these findings.

Hospital volume-mortality association after esophagectomy for cancer: a systematic review and meta-analysis.

BACKGROUND: Postoperative mortality plays an important role in evaluating the surgical safety of esophagectomy. Although postoperative mortality after esophagectomy is partly influenced by the yearly hospital surgical case volume (hospital volume), this association remains unclear. METHODS: Studies assessing the association between hospital volume and postoperative mortality in patients who underwent esophagectomy for esophageal cancer were searched for eligibility. Odds ratios were pooled for the highest versus lowest categories of hospital volume using a random effects model. The dose-response association between hospital volume and the risk of postoperative mortality was analyzed. The study protocol was registered with PROSPERO. RESULTS: Fifty-six studies including 385 469 participants were included. A higher-volume hospital significantly reduced the risk of postesophagectomy mortality by 53% compared with their lower-volume counterparts (odds ratio, 0.47; 95% CI: 0.42-0.53). Similar results were found in subgroup analyses. Volume-outcome analysis suggested that postesophagectomy mortality rates remained roughly stable after the hospital volume reached a plateau of 45 esophagectomies per year. CONCLUSIONS: Higher-volume hospitals had significantly lower postesophagectomy mortality rates in patients with esophageal cancer, with a threshold of 45 esophagectomies per year for a high-volume hospital. This remarkable negative correlation showed the benefit of a better safety in centralization of esophagectomy to a high-volume hospital.

Extraction, structural characterization and immunoactivity of glucomannan type polysaccahrides from Lilium brownii var. viridulum Baker.

Homogeneous polysaccharide (LBP) was extracted and purified from the bulblets of Lilium brownii var. viridulum Baker with a molecular weight of 312 kDa. The monosaccharides are composed of mannose and glucose, and the corresponding molar ratios are 0.582 and 0.418, respectively. FT-IR, LC-MS, NMR, GC-MS and HPAEC were used to analyze the functional groups, glycosidic linkages and chemical structure of LBP, which was a 1-4-linked glucomannan and contained a dodecasaccharide repeating units of →4)-ß-D-Manp-(1 â†’ 4)-ß-D-Manp-(1 â†’ 4)-ß-D-Manp-(1 â†’ 4)-ß-D-Glcp-(1 â†’ 4)-ß-D-Manp-(1 â†’ 4)-ß-D-Manp-(1 â†’ 4)-ß-D-Glcp-(1 â†’ 4)-α-D-Glcp-(1 â†’ 4)-ß-D-Glcp-(1 â†’ 4)-ß-D-Glcp-(1 â†’ 4)-ß-D-Manp-(1 â†’ 4)-ß-D-Manp-(1 â†’ . In vitro experimental results showed that LBP had noble biocompatibility, and a low dose of 5 µg/mL LBP significantly up-regulated the mRNA expression of TNF-α, iNOS, IL-6, IL-1ß and Toll-like receptors family (TLRs) in RAW 264.7 cells. In conclusion, LBP played an important role in immunomodulation, and further studies on the specific immunomodulatory mechanisms of LBP on RAW 264.7 cells are still needed.

Experimental study of modified Tavis-Cummings model with directly-coupled superconducting artificial atoms.

The Tavis-Cummings model is intensively investigated in quantum optics and has important applications in generation of multi-atom entanglement. Here, we employ a superconducting circuit quantum electrodynamic system to study a modified Tavis-Cummings model with directly-coupled atoms. In our device, three superconducting artificial atoms are arranged in a chain with direct coupling through fixed capacitors and strongly coupled to a transmission line resonator. By performing transmission spectrum measurements, we observe different anticrossing structures when one or two qubits are resonantly coupled to the resonator. In the case of the two-qubit Tavis-Cummings model without qubit-qubit interaction, we observe two dips at the resonance point of the anticrossing. The splitting of these dips is determined by Δ λ=2g12+g32, where g1 and g3 are the coupling strengths between Qubit 1 and the resonator, and Qubit 3 and the resonator, respectively. The direct coupling J12 between the two qubits results in three dressed states in the two-qubit Tavis-Cummings model at the frequency resonance point, leading to three dips in the transmission spectrum. In this case, the distance between the two farthest and asymmetrical dips, arising from the energy level splitting, is larger than in the previous case. The frequency interval between these two dips is determined by the difference in eigenvalues (Δ λ=ε 1+-ε 1-), obtained through numerical calculations. What we believe as novel and intriguing experimental results may potentially advance quantum optics experiments, providing valuable insights for future research.

Polysaccharide of Alocasia cucullata Exerts Antitumor Effect by Regulating Bcl-2, Caspase-3 and ERK1/2 Expressions during Long-Time Administration.

OBJECTIVE: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism. METHODS: B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. RESULTS: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. CONCLUSIONS: Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.

Radiomic Analysis Based on Gd-EOB-DTPA Enhanced MRI for the Preoperative Prediction of Ki-67 Expression in Hepatocellular Carcinoma.

RATIONALE AND OBJECTIVES: To develop and validate a random forest model based on radiomic features in Gd-EOB-DTPA enhanced MRI for predicting the Ki-67 expression in solitary HCC. MATERIALS AND METHODS: This retrospective study analyzed 258 patients with solitary HCC. Significant clinicoradiological factors were identified through univariate and multivariate analyses for distinguishing HCC with high (>20%) and low (≤20%) Ki-67 expression. Radiomic features were extracted at Gd-EOB-DTPA enhanced MRI. The recursive feature elimination (RFE) strategy was employed to screen robust radiomic features, and the Random Forest (RF) algorithm was utilized to rank radiomic features and construct prediction models. The AUC, accuracy, precision, recall, and f1-score were used to evaluate the performance of RF models. RESULTS: Multivariate analysis identified serum AFP level, tumor size, growth type, and peritumoral enhancement as independent predictors for HCC with high Ki-67 expression. The clinicoradiological-radiomic model that incorporated the clinicoradiological predictors and the top ten radiomic features outperformed the clinicoradiological model in the training set (AUCs 0.876 vs. 0.780; p < 0.001), though the test set did not have a statistical significance (AUCs 0.809 vs. 0.723; p = 0.123). The addition of clinicoradiological predictors did not yield a significant improvement in the performance of radiomic features in both sets (training, p = 0.692; test, p = 0.229). Decision curve analysis further confirmed the clinical utility of the RF models. CONCLUSION: The RF models based on radiomic features of Gd-EOB-DTPA enhanced MRI achieved satisfactory performance in preoperatively predicting Ki-67 expression in HCC.

Association between MC1R gene and coat color segregation in Shanxia long black pig and Lulai black pig.

BACKGROUND: Coat color, as a distinct phenotypic characteristic of pigs, is often subject to preference and selection, such as in the breeding process of new breed. Shanxia long black pig was derived from an intercross between Berkshire boars and Licha black pig sows, and it was bred as a paternal strain with high-quality meat and black coat color. Although the coat color was black in the F1 generation of the intercross, it segregated in the subsequent generations. This study aims to decode the genetic basis of coat color segregation and develop a method to distinct black pigs from the spotted in Shanxia long black pig. RESULTS: Only a QTL was mapped at the proximal end of chromosome 6, and MC1R gene was picked out as functional candidate gene. A total of 11 polymorphic loci were identified in MC1R gene, and only the c.67_68insCC variant was co-segregating with coat color. This locus isn't recognized by any restriction endonuclease, so it can't be genotyped by PCR-RFLP. The c.370G > A polymorphic locus was also significantly associated with coat color, and has been in tightly linkage disequilibrium with the c.67_68insCC. Furthermore, it is recognized by BspHI. Therefore, a PCR-RFLP method was set up to genotype this locus. Besides the 175 sequenced individuals, another more 1,391 pigs were genotyped with PCR-RFLP, and all of pigs with GG (one band) were black. CONCLUSION: MC1R gene (c.67_68insCC) is the causative gene (mutation) for the coat color segregation, and the PCR-RFLP of c.370G > A could be used in the breeding program of Shanxia long black pig.

Autopsy analysis reveals increased macrophage infiltration and cell apoptosis in COVID-19 patients with severe pulmonary fibrosis.

Clinical data indicates that SARS-CoV-2 infection-induced respiratory failure is a fatal condition for severe COVID-19 patients. However, the pathological alterations of different types of respiratory failure remained unknown for severe COVID-19 patients. This study aims to evaluate whether there are differences in the performance of various types of respiratory failure in severe COVID-19 patients and investigate the pathological basis for these differences. The lung tissue sections of severe COVID-19 patients were assessed for the degree of injury and immune responses. Transcriptome data were used to analyze the molecular basis in severe COVID-19 patients. Severe COVID-19 patients with combined oxygenation and ventilatory failure presented more severe pulmonary fibrosis, airway obstruction, and prolonged disease course. The number of M2 macrophages increased with the degree of fibrosis in patients, suggesting that it may be closely related to the development of pulmonary fibrosis. The co-existence of pro-inflammatory and anti-inflammatory cytokines in the pulmonary environment could also participate in the progression of pulmonary fibrosis. Furthermore, the increased apoptosis in the lungs of COVID-19 patients with severe pulmonary fibrosis may represent a critical factor linking sustained inflammatory responses to fibrosis. Our findings indicate that during the extended phase of COVID-19, antifibrotic and antiapoptotic treatments should be considered in conjunction with the progression of the disease.

Effect of Naoluoxintong formula and its split prescriptions on cerebral vascular regeneration in rats with the cerebral ischemia-reperfusion.

OBJECTIVE: To observe regulatory effect of Naoluoxintong formula (, NLXT) and its split prescriptions on vascular regeneration of rats suffering from cerebral ischemia-reperfusion (IR) syndrome of Qi deficiency with blood stasis (QDBS). METHODS: NLXT is the representative prescription of Yiqi Huoxue Tongluo decoction, and NLXT is divided into Yiqi herbs and Huoxue Tongluo herbs according to their efficacies. One hundred and eight specific-pathogen-free, clean-grade, Sprague-Dawley male rats were selected to prepare the classical rat model with QDBS due to middle artery ischemia-reperfusion using the multi-factor compound simulation approach. The animals were classified into sham operation (S), model (M), Nimodping (NMDP), NLXT, YQ and HXTL groups, each having 18 rats. Cerebral ischemia was reperfused after 2 h, and 24 h later, they were administered traditional Chinese medicine treatment for 14 d twice a day. Angiogenesis changes after NLXT administration to middle cerebral artery occlusion-reperfusion (MCAO/R) rats with QDBS were analyzed using the neurological deficit score and hematoxylin-eosin staining. Cerebral infarct area by 2,3,5-Triphenyltetrazolium chloride was detected, and the ultrastructure of the blood vessel in the ischemic frontoparietal cortex was observed by transmission electron microscopy. Angiopoietin 1 (Ang1), angiopoietin 2 (Ang2), vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), platelet endothelial cell adhesion molecule-1 (CD31), angiopoietin receptor 2 (Tie2), and P38 mitogen-activated protein kinase (MAPK) protein levels in the frontal and parietal cortex were quantified by immunofluorescence, reverse transcription-polymerase chain reaction, and Western blotting assays. RESULTS: Relative to the S group, VEGFA and VEGFR2 levels in the frontal and parietal cortex of group M were increased, and Ang1, Ang2, Tie2, CD31, and p38 MAPK levels remarkably increased (P < 0.05); cerebral infarct area was significant and pathological morphology and ultrastructure damage was obvious. Relative to the group M, VEGFA, VEGFR2, CD31, Ang1, Ang2, and Tie2 expression of group NLXT and NMDP remarkably elevated (P < 0.05) and infarct focus, pathological morphology and ultrastructure were significantly improved; VEGFA and VEGFR2 levels in the groups YQ and HXTL increased, and Ang1, Ang2, CD31, and Tie2 levels remarkably increased (P < 0.05); p38 MAPK levels in the three treatment groups decreased (P < 0.05). Relative to the group NLXT, the expression levels of p38 MAPK in group YQ and group HXTL were significantly increased, and the expression levels of other indicators were significantly decreased (P < 0.05). CONCLUSION: NLXT can promote the angiogenesis of the rat model of MCAO/R with QDBS by activating VEGFA and inhibiting P38 MAPK, and the effect is better than that of split prescription groups.

An explainable machine learning based prediction model for Alzheimer's disease in China longitudinal aging study.

Alzheimer's disease (AD) is the most common cause of dementia. Accurate prediction and diagnosis of AD and its prodromal stage, i.e., mild cognitive impairment (MCI), is essential for the possible delay and early treatment for the disease. In this paper, we adopt the data from the China Longitudinal Aging Study (CLAS), which was launched in 2011, and includes a joint effort of 15 institutions all over the country. Four thousand four hundred and eleven people who are at least 60 years old participated in the project, where 3,514 people completed the baseline survey. The survey collected data including demographic information, daily lifestyle, medical history, and routine physical examination. In particular, we employ ensemble learning and feature selection methods to develop an explainable prediction model for AD and MCI. Five feature selection methods and nine machine learning classifiers are applied for comparison to find the most dominant features on AD/MCI prediction. The resulting model achieves accuracy of 89.2%, sensitivity of 87.7%, and specificity of 90.7% for MCI prediction, and accuracy of 99.2%, sensitivity of 99.7%, and specificity of 98.7% for AD prediction. We further utilize the SHapley Additive exPlanations (SHAP) algorithm to visualize the specific contribution of each feature to AD/MCI prediction at both global and individual levels. Consequently, our model not only provides the prediction outcome, but also helps to understand the relationship between lifestyle/physical disease history and cognitive function, and enables clinicians to make appropriate recommendations for the elderly. Therefore, our approach provides a new perspective for the design of a computer-aided diagnosis system for AD and MCI, and has potential high clinical application value.

Extraction of Diatom DNA from Water Samples and Tissues.

Diatom testing is an essential auxiliary means in forensic practice to determine whether the corpse drowned in water and to infer the drowning location. Diatom testing is also an important research content in the field of the environment and plankton. The diatom molecular biology testing technology, which focuses on diatom DNA as the primary research object, is a new method of diatom testing. Diatom DNA extraction is the basis of diatom molecular testing. At present, the kits commonly used for diatom DNA extraction are expensive, which increases the cost of carrying out related research. Our laboratory improved the general whole blood genomic DNA rapid extraction kit and obtained a satisfactory diatom DNA extraction effect, thus providing an alternative economical and affordable DNA extraction solution based on glass beads for related research. The diatom DNA extracted using this protocol could satisfy many downstream applications, such as PCR and sequencing.

Confined Heterojunction in Hollow-Structured TiO2 and Its Directed Effect in Photodriven Seawater Splitting.

The high salinity of seawater often strongly affects the activity and stability of photocatalysts utilized for photodriven seawater splitting. The current investigation is focused on the photocatalyst H-TiO2/Cu2O, comprised of hydroxyl-enriched hollow mesoporous TiO2 microspheres containing incorporated Cu2O nanoparticles. The design of H-TiO2/Cu2O is based on the hypothesis that the respective hollow and mesoporous structure and hydrophilic surfaces of TiO2 microspheres would stabilize Cu2O nanoparticles in seawater and provide efficient and selective proton adsorption. H-TiO2/Cu2O shows hydrogen production performances of 45.7 mmol/(g·h) in simulated seawater and 17.9 mmol/(g·h) in natural seawater, respectively. An apparent quantum yield (AQY) in hydrogen production of 18.8% in water (and 14.9% in natural seawater) was obtained at 365 nm. Moreover, H-TiO2/Cu2O displays high stability and can maintain more than 90% hydrogen evolution activity in natural seawater for 30 h. A direct mass- and energy- transfer mechanism is proposed to clarify the superior performance of H-TiO2/Cu2O in seawater splitting.

Dual Pd-Acid Sites Confined in a Hierarchical Core-Shell Structure for Hydrogenation of Nitrobenzene.

A core-shell structured Pd@TS-1@meso-SiO2 catalyst with confined Pd nanometals has been fabricated by one-pot synthesis, impregnation method and sol-gel method. With the promotion of acid sites and protection of mesoporous silica shell, Pd@TS-1@meso-SiO2 shows higher activity than commercial comparison and higher stability than sample without mesoporous silica shell in the hydrogenation of nitrobenzene. The schematic illustration of the synergy effect is also proposed.

Efficacy of PD-1 inhibitors for colorectal cancer and polyps in Lynch syndrome patients.

BACKGROUND: Programmed death-1 (PD-1) inhibitor is effective for colorectal cancer (CRC) with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H). We aimed to explore its effects on CRCs and colonic polyps in Lynch syndrome (LS) patients. METHODS: LS patients with CRC who had evaluable tumours and received at least 2 cycles of PD-1 inhibitors were retrospectively included. PD-1 inhibitors were given as a monotherapy or in combination with other therapies, including anticytotoxic T-lymphocyte-associated antigen-4 treatment, radiotherapy, chemotherapy, and targeted therapy. Correlations of treatment responses with clinicopathological characteristics and genomic profiles were analysed. RESULTS: A total of 75 LS patients were included, with a median age of 39 years. The median duration of follow-up was 27 months (range, 3-71). The objective response rate (ORR) was 70.7%, including 28.0% (n = 21) complete responses and 42.7% (n = 32) partial responses. Four of five cases of LS CRCs displaying proficient MMR (pMMR) or microsatellite stable (MSS) were not responsive. Mucinous/signet-ring cell differentiation was associated with a lower ORR (P = 0.013). The 3-year overall survival and progression-free survival were 91.2% and 82.2%, respectively. A polyp was detected in 26 patients during surveillance. Seven adenomas disappeared after treatment, and they were all larger than 7 mm. CONCLUSION: PD-1 inhibitors are highly effective for dMMR and MSI-H LS CRCs, but not for pMMR or MSS LS CRCs or mucinous/signet-ring cell CRC. Large LS adenomas may also be eliminated by anti-PD-1 treatment. DATA AVAILABILITY STATEMENT: Due to the privacy of patients, the related data cannot be available for public access but can be obtained from Pei-Rong Ding (dingpr@sysucc.org.cn) upon reasonable request. The key raw data have been uploaded to the Research Data Deposit public platform (www.researchdata.org.cn).

Nivalenol disrupts mitochondria functions during porcine oocyte meiotic maturation.

Oocyte maturation is important for fertility in mammals, since the quality of oocytes directly affects fertilization, embryo attachment and survival. Nivalenol is widely present in nature as a common toxin that contaminates grain and feed, and it has been reported to cause acute toxicity, immunotoxicity, reproductive toxicity and carcinogenic effects. In this study, we explored the impact of nivalenol on the porcine oocyte maturation and its possible mechanisms. The extrusion of the first polar body was significantly inhibited after incubating oocytes with nivalenol. Meanwhile, nivalenol exposure led to the abnormal distribution of mitochondria, aberrant calcium concentration and the reduction of membrane potential caused a significant decrease in the capacity of mitochondria to generate ATP. In addition, nivalenol induced oxidative stress, and the level of ROS was significantly increased in the nivalenol-treated group, which was confirmed by the perturbation of oxidative stress-related genes. We found that nivalenol-treated oocytes showed positive Annexin-V and γH2A.X signals, indicating the occurrence of apoptosis and DNA damage. In all, our data suggest that nivalenol disrupted porcine oocyte maturation through its effects on mitochondria-related oxidative stress, apoptosis and DNA damage.

[Chemical constituents of roots of Rodgersia aesculifolia].

The chemical compositions of Rodgersia aesculifolia were isolated and purified using a combination of silica gel, reverse phase silica gel, Sephadex LH-20 column chromatography, and semi-preparative HPLC. The structures were determined according to the physicochemical properties and spectroscopic data. The MTT method and the ABTS kit were used to measure the cytotoxicity and antioxidant capacity of all isolates, respectively. Thirty-four compounds were isolated from R. aesculifolia and elucidated as stigmastane-6ß-methoxy-3ß,5α-diol(1), stigmastane-3ß,5α,6ß triol(2), ß-sitosterol(3), ß-daucosterol(4), stigmast-4-en-3-one(5), bergenin(6), 11-ß-D-glucopyranosyl-bergenin(7), 11-O-galloybergenin(8), 1,4,6-tri-O-galloyl-ß-D-glucose(9), gallic acid(10), 3,4-dihydroxybenzoic acid methyl ester(11), ethyl gallate(12), ethyl 3,4-dihydroxybenzoate(13), caffeic acid ethyl ester(14), p-hydroxybenzeneacetic acid(15), 4-hydroxybenzoic acid(16), 2,3-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)-propan-1-one(17), 3,7-dimethyl-2-octene-1,7-diol(18), crocusatin-B(19), neroplomacrol(20), geniposide(21), 3-hydroxyurs-12-en-27-oic acid(22), 3ß-trans-p-coumaroyloxy-olean-12-en-27-oic acid(23), aceriphyllic acid G(24), isolariciresinol(25), trans-rodgersinine B(26), cis-rodgersinine A(27), neo-olivil(28),(7S,8R)-dihydro-3'-hydroxy-8-hydroxy-methyl-7-(4-hydroxy-3-methoxy phenyl)-1'-benzofuranpropanol(29), 5,3',4'-trihydroxy-7-methoxyflavanone(30), quercetin 3-rutinoside(31), catechin-[8,7-e]-4ß-(3,4-dihydroxy-phenyl)-dihydro-2(3H)-pyranone(32), ethyl α-L-arabino-furanoside(33), and l-linoleoylglycerol(34). One new compound was discovered(compound 1), 25 compounds were first isolated from R. aesculifolia, and 22 compounds were first isolated from the Rodgersia plant. The results indicated that compounds 22-24 possessed cytotoxicity for HepG2, MCF-7, HCT-116, BGC-823, and RAFLS cell lines(IC_(50) ranged from 5.89 µmol·L~(-1) to 20.5 µmol·L~(-1)). Compounds 8-14 and 30-32 showed good antioxidant capacity, and compound 9 showed the strongest antioxidant activity with IC_(50) of(2.00±0.12) µmol·L~(-1).