Cmtm4 deficiency exacerbates colitis by inducing gut dysbiosis and S100A8/9 expression.

The dysfunction of innate immunity components is one of the major drivers for ulcerative colitis (UC), and increasing reports indicate that gut microbiome serves as an intermediate between genetic mutations and UC development. Here, we find that the IL-17 receptor subunit, CMTM4, is reduced in UC patients and DSS-induced colitis. The deletion of CMTM4 (Cmtm4-/-) in mice leads to a higher susceptibility to DSS-induced colitis in comparison to wildtype, and the gut microbiome significantly changes in the composition. The causal role of gut microbiome is confirmed with co-housing experiment. We further identify that S100a8/9 is significantly up-regulated in Cmtm4-/- colitis, with the block of its receptor RAGE that reverses the phenotype associated with the CMTM4 deficiency. CMTM4 deficiency rather suppresses S100a8/9 expression in vitro via the IL17 pathway, further supporting that the elevation of S100a8/9 in vivo is most likely a result of microbial dysbiosis. Taken together, the results suggest that CMTM4 is involved in the maintenance of the intestinal homeostasis, suppression of S100a8/9, and prevention of the colitis development. Our study further shows CMTM4 as a crucial innate immunity component, confirming its important role in the UC development and providing insights into potential targets for development of future therapies.

Efficient caproic acid production from lignocellulosic biomass by bio-augmented mixed microorganisms.

Producing caproic acid via carboxylate platform is an environmentally-friendly approach for treating lignocellulosic agricultural waste. However, its implementation is still challenged by low product yields and selectivity. A microbiome named cellulolytic acid-producing microbiome (DCB), proficient in producing cellulolytic acid, was successfully acquired and shows promise for producing high-level caproic acid. In this study, a bioaugmentation method utilizing Clostridium kluyveri is proposed to enhance caproic acid yield of DCB using rice straw. With exogenous ethanol, bioaugmentation with Clostridium kluyveri significantly improved the caproic acid concentration and selectivity by 7 times and 4.5 times, achieving 12.9 g/L and 55.1 %, respectively. The addition of Clostridium kluyveri introduced reverse ß-oxidation pathway, a more efficient caproic acid production pathway. Meanwhile, bioaugmentation enriched the bacteria proficient in degrading straw and producing short-chain fatty acids, providing more substrates for caproic acid production. This study provides potential bioaugmentation strategies for optimizing caproic acid yield from lignocellulosic biomass.

Prelimbic cortical pyramidal neurons to ventral tegmental area projections promotes arousal from sevoflurane anesthesia.

AIMS: General anesthesia has been used in surgical procedures for approximately 180 years, yet the precise mechanism of anesthetic drugs remains elusive. There is significant anatomical connectivity between the ventral tegmental area (VTA) and the prelimbic cortex (PrL). Projections from VTA dopaminergic neurons (VTADA ) to the PrL play a role in the transition from sevoflurane anesthesia to arousal. It is still uncertain whether the prelimbic cortex pyramidal neuron (PrLPyr ) and its projections to VTA (PrLPyr -VTA) are involved in anesthesia-arousal regulation. METHODS: We employed chemogenetics and optogenetics to selectively manipulate neuronal activity in the PrLPyr -VTA pathway. Electroencephalography spectra and burst-suppression ratios (BSR) were used to assess the depth of anesthesia. Furthermore, the loss or recovery of the righting reflex was monitored to indicate the induction or emergence time of general anesthesia. To elucidate the receptor mechanisms in the PrLPyr -VTA projection's impact on anesthesia and arousal, we microinjected NMDA receptor antagonists (MK-801) or AMPA receptor antagonists (NBQX) into the VTA. RESULTS: Our findings show that chemogenetic or optogenetic activation of PrLPyr neurons prolonged anesthesia induction and promoted emergence. Additionally, chemogenetic activation of the PrLPyr -VTA neural pathway delayed anesthesia induction and promoted anesthesia emergence. Likewise, optogenetic activation of the PrLPyr -VTA projections extended the induction time and facilitated emergence from sevoflurane anesthesia. Moreover, antagonizing NMDA receptors in the VTA attenuates the delayed anesthesia induction and promotes emergence caused by activating the PrLPyr -VTA projections. CONCLUSION: This study demonstrates that PrLPyr neurons and their projections to the VTA are involved in facilitating emergence from sevoflurane anesthesia, with the PrLPyr -VTA pathway exerting its effects through the activation of NMDA receptors within the VTA.

Sevoflurane exerts antidepressant-like effects via the BDNF-TrkB pathway.

Depression has emerged as the predominant psychiatric affliction affecting individuals. Prior research has substantiated the antidepressant properties exhibited by numerous anesthetics. Sevoflurane, a widely utilized inhalant anesthetic in clinical practice, remains relatively uncharted in terms of its specific antidepressant effects. In this study, we used open field test, forced swimming test and novelty-suppressed feeding test to investigate the anxiety and depression-like behaviors in C57BL/6 mice following the inhalation of sevoflurane. We then used western blotting to scrutinized the expression levels of proteins associated with the brain-derived neurotrophic factor (BDNF)-tryosine receptor kinase B (TrkB) pathway in the hippocampus and prefrontal cortex. To further investigate whether sevoflurane exerts antidepressant-like effects via the BDNF-TrkB pathway, we downregulated TrkB expression by administering siRNA into the lateral ventricle. We found that the inhalation of 2.5 % sevoflurane exerted a significant antidepressant-like effect, accompanied by an elevation in p-TrkB expression levels in the hippocampus and prefrontal cortex. Intriguingly, this antidepressant-like effect was abrogated following the downregulation of TrkB expression through the microinjection of siRNA into the lateral ventricle. In conclusion, this study provides evidence supporting the notion that sevoflurane exerts its antidepressant-like effect via the BDNF-TrkB signaling pathway.

Ag3PO4 enables the generation of long-lived radical cations for visible light-driven [2 + 2] and [4 + 2] pericyclic reactions.

Photocatalytic redox reactions are important for synthesizing fine chemicals from olefins, but the limited lifetime of radical cation intermediates severely restricts semiconductor photocatalysis efficiency. Here, we report that Ag3PO4 can efficiently catalyze intramolecular and intermolecular [2 + 2] and Diels-Alder cycloadditions under visible-light irradiation. The approach is additive-free, catalyst-recyclable. Mechanistic studies indicate that visible-light irradiation on Ag3PO4 generates holes with high oxidation power, which oxidize aromatic alkene adsorbates into radical cations. In photoreduced Ag3PO4, the conduction band electron (eCB-) has low reduction power due to the delocalization among the Ag+-lattices, while the particle surfaces have a strong electrostatic interaction with the radical cations, which considerably stabilize the radical cations against recombination with eCB-. The radical cation on the particle's surfaces has a lifetime of more than 2 ms, 75 times longer than homogeneous systems. Our findings highlight the effectiveness of inorganic semiconductors for challenging radical cation-mediated synthesis driven by sunlight.

A visible-light-catalyzed sulfonylation reaction of an aryl selenonium salt via an electron donor-acceptor complex.

An efficient synthesis of sulfone structures through selenonium salts and sodium sulfinates was developed. Under the irradiation of a blue LED lamp, the two substrates generate aryl and sulfonyl radicals through the activation of the intermediate electron donor acceptor (EDA) complex, thereby synthesizing aromatic, heteroaromatic and aliphatic sulfones in medium to good yields. The advantages of this strategy are metal-free, mild conditions and the leaving group is recycled to construct new selenonium salts.

Efficacy of non-pharmacological interventions for primary dysmenorrhoea: a systematic review and Bayesian network meta-analysis.

OBJECTIVES: To assess the relative benefits of various non-pharmacological interventions on treating primary dysmenorrhoea within a network meta-analysis. STUDY DESIGN: Systematic review and Bayesian network meta-analysis. INCLUSION CRITERIA: Randomised controlled trial involving patient with primary dysmenorrhoea and received non-pharmacological interventions. DATA SOURCES: Four databases (Medline, Embase, Cochrane Library and Web of Science) were searched from inception to October first, 2022. RISK-OF-BIAS ROB ASSESSMENT: RoB 2.0 assessment tools was used to assess the risk of bias in the included studies. SYNTHESIS OF RESULTS: Conventional meta-analysis was conducted by pairwise comparison between non-pharmacological therapy and control treatment. The Bayesian network meta-analysis was conducted by the Aggregate Data Drug Information System Software based on the consistency or inconsistency model, and rank probability was used to indicate the priority of non-pharmacological therapy. RESULTS: 33 studies involving eight non-pharmacological interventions were included. With regard to conventional meta-analysis, we selected Visual Analogue Scale (VAS) as primary outcome to evaluate the pain intensity. The result showed that eight interventions (Exercise, Herb, Acupuncture, Aromatherapy, Transcutaneous Electrical Nerve Stimulation, Topical heat, Acupressure, Yoga) displayed positive effect on reduction of menstrual pain compared with placebo or no treatment. A Bayesian network meta-analysis revealed that exercise -3.20 (95% CI -4.01 to -2.34), acupuncture -2.90 (95% CI -3.97 to -2.85) and topical heat -2.97 (95% CI -4.66 to -1.29) probably resulted in a reduction in pain intensity (VAS) . CONCLUSIONS: Non-pharmacological interventions may result in a reduction or slight reduction in pain intensity compared with no treatment or placebo. Specifically, exercise and acupuncture are considered as potentially effective non-pharmacological treatments in short-term treatment. Indeed, larger and better methodological quality research is needed. TRIAL REGISTRATION NUMBER: CRD42022351021.

Large-Scale Bio-Inspired FPGA Models for Path Planning.

The hippocampus provides significant inspiration for spatial navigation and memory in both humans and animals. Constructing large-scale spiking neural network (SNN) models based on the biological neural systems is an important approach to comprehend the computational principles and cognitive function of the hippocampus. Such models are usually implemented on neuromorphic computing platforms, which often have limited computing resources that constrain the achievable scale of the network. This work introduces a series of digital design methods to realize a Field-Programmable Gate Array (FPGA) friendly SNN model. The methods include FPGA-friendly nonlinear calculation modules and a fixed-point design algorithm. A brain-inspired large-scale SNN of ∼21 k place cells for path planning is mapped on FPGA. The results show that the path planning tasks in different environments are finished in real-time and the firing activities of place cells are successfully reproduced. With these methods, the achievable network size on one FPGA chip is increased by 1595 times with higher resource usage efficiency and faster computation speed compared to the state-of-the-art.

Predicting pathological complete response based on weakly and semi-supervised joint learning from breast cancer MRI.

Neoadjuvant chemotherapy (NAC) is the standard treatment for breast cancer patients. Patients achieving complete pathological response (pCR) after NAC usually have a good prognosis. However, automatic pCR prediction has been a challenging problem due to lacking well annotations in 3D MRI. Thus far, unifying different annotation information to predict the tumor's early response to NAC has not been systematically addressed. This paper proposes a weakly and semi-supervised joint learning method that integrates attentional features from multi-parametric MRI with radiomic features for predicting pCR to NAC in breast cancer patients. The attention-based multi-instance learning (MIL) is first developed to generate informative MRI bag-level features and mine key instances. The mean-teacher framework is then employed to segment tumor regions in a semi-supervised setting for extracting radiomic features. We perform experiments on 442 patients' data and show that our method achieves an AUC value of 0.85 in pCR prediction, which is superior to comparative methods. It is also shown that learning from multi-parametric MRI outperforms that of single-parameter MRI in pCR prediction.

Symptom clusters and characteristics of cervical cancer patients receiving concurrent chemoradiotherapy: A cross-sectional study.

Background: Cervical cancer patients have a high symptom burden during concurrent chemoradiotherapy (CCRT) and urgently need precise symptom management strategies. Nonetheless, the symptom profile and influencing factors are unclear. Methods: A total of 234 patients with cervical cancer who underwent CCRT in a tertiary care hospital clinical oncology center in Guangxi Zhuang Autonomous Region from March 2022 to March 2023 were included in the study. The general information questionnaire, M.D. Anderson symptom inventory, Fatigue Scale-14, Pittsburgh Sleep Quality Index, and grip strength test were used for the investigation. Symptom clusters were extracted by exploratory factor analysis, and latent profile analysis was performed using Mplus 8.0 software. Multinomial logistic regression was used to explore the factors influencing the potential categories of symptom clusters. Results: Exploratory factor analysis extracted four symptom clusters: a fatigue-related symptom cluster, a gastrointestinal-related symptom cluster, a mood-related symptom cluster, and a physical-related symptom cluster, of which the fatigue-related symptom cluster was more severe and was divided into three potential categories: low fatigue-good muscle fitness type (25.63%), general fatigue-moderate muscle fitness type (68.37%) and high fatigue-low muscle fitness type (6%). Multinomial logistic regression analysis showed that hemoglobin levels, tumor stage, absence of complications, and unemployment were factors influencing the fatigue-related symptom cluster in patients undergoing CCRT for cervical cancer. Conclusions: Cervical cancer patients experience multiple symptom clusters during CCRT. Different characteristics appeared in different clusters. Among them, fatigue-related symptom clusters were more severe and heterogeneous. In clinical practice, we should pay attention to and use high symptom feature predictors, focusing on the core symptoms that play a dominant role, achieving early identification and management, and reducing patients' symptom burden.

Transcranial alternating current stimulation ameliorates emotional attention through neural oscillations modulation.

Background: Numerous clinical reports have suggested that psychopathy like schizophrenia, anxiety and depression is accompanied by early attentional abnormalities in emotional processing. Recently, the efficacy of transcranial alternating current stimulation (tACS) in changing emotional functioning has been repeatedly observed and demonstrated a causal relationship between endogenous oscillations and emotional processing. Aims: Up to now, tACS effects on emotional attention have not yet been tested. To assess such ability, we delivered active-tACS at individual alpha frequency (IAF), 10 Hz or sham-tACS for 7 consecutive days in the bilaterally dorsolateral prefrontal cortex (dlPFC) to totally 79 healthy participants. Results: IAF-tACS group showed significant alpha entrainment at-rest, especially in open state around stimulation area and showed an obvious advantage compared to 10 Hz-tACS. Event-related potential revealed a significant larger P200 amplitude after active-tACS and IAF group showed wider range of emotions than 10 Hz-tACS, indicating the attentional improvement in facial emotion processing. A notable positive correlation between alpha power and P200 amplitude provided an electrophysiological interpretation regarding the role of tACS in emotional attention modulation instead of somatosensory effects. Conclusion: These results support a seminal outcome for the effect of IAF-tACS on emotional attention modulation, demonstrating a feasible and individual-specific therapy for neuropsychiatric disorders related to emotion processing, especially regarding oscillatory disturbances.

Numerical prediction of glass molding process for 3D curved screen.

With the rapid development of consumer electronics industry, the demand for 3D curved screen in industry is also growing. At present, 3D curved screen is mass produced through glass molding process. However, due to the complex rheological properties of glass melt and the intricate deformation mechanism of glass molding process, the final geometry of the screen is difficult to predict. In this paper, the glass molding process for 3D curved screen is analyzed by finite element transient analysis. The trend of screen shape change is obtained and the final geometry of the screen is predicted. The results show that geometric fillet and rheological parameters have great influence on the flow of glass melt in glass molding process. This study is helpful for the selection of parameters of glass molding process and the design of 3D curved screen.

Ventrolateral periaqueductal gray GABAergic neurons promote arousal of sevoflurane anesthesia through cortico-midbrain circuit.

The mechanism of general anesthesia remains elusive. The ventrolateral periaqueductal gray (vlPAG) in the midbrain regulates sleep and awake states. However, the role of vlPAG and its circuits in anesthesia is unclear. We utilized opto/chemogenetics, righting reflex, and electroencephalographic recording to assess consciousness changes. We employed fiber photometry to measure the activity of neurons and neurotransmitters. As a result, photometry recording showed that the activity of GABA neurons in vlPAG decreased during sevoflurane anesthesia and was reactivated after anesthesia. Activating GABAergic neurons in vlPAG promoted arousal during anesthesia, while inhibiting them delayed this process. Furthermore, medial prefrontal cortex (mPFC) to vlPAG pyramidal neurons projections and vlPAG to ventral tegmental area (VTA) GABAergic projections played a prominent role in the anesthesia-awake transition. GABA neurotransmitter activity of VTA synchronized with mPFC-vlPAG pyramidal neuron projections. Therefore, the cortico-midbrain circuits centered on vlPAG GABAergic neurons exert an arousal-promoting effect during sevoflurane anesthesia.

Mental health changes in elderly patients undergoing non-cardiac surgery during the COVID-19 pandemic in China.

BACKGROUND: The COVID-19 pandemic has a heavy impact on the mental health of elderly surgical patients worldwide. In particular, the elderly patients faced considerable psychological stress due to various environmental and medical factors during the outbreak. This study aims to examine changes in mental health trends among non-cardiac surgical patients aged 65 and above in China during the COVID-19 pandemic. METHODS: This multi-center, convenient sampling, longitudinal observational study was conducted from April 1, 2020 to April 30, 2022. Primary outcome was the prevalence of postoperative depression. Secondary outcome was the prevalence of postoperative anxiety. Follow-up was conducted separately at 7 days and 30 days after surgery. Depression symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9) scale. Anxiety symptoms were assessed using Generalized Anxiety Disorder-7 (GAD-7) scale, with scores of ≥5 defining positive depression or anxiety symptoms. Multivariate logistic regression analysis was used to investigate risk factors of mental health status in more elderly patients undergoing non-cardiac surgery. RESULTS: A total of 4639 patients were included, of whom 2279 (46.0 %) were male, 752 (15.2 %) were over the age of 75, and 4346 (93.7 %) were married. The monthly prevalence trends demonstrated that compared to the outbreak period, a significant reduction in the prevalence of depression and anxiety symptoms in elderly patients who underwent surgery during the post-pandemic period. In post-pandemic period, a statistically significant decrease in the prevalence of all severity depression and anxiety patients was noted at the 7-day follow-up, but no significant decrease was observed for severe depression and anxiety in the 30-day follow-up. In COVID-19 low-risk area, a significant overall decrease in prevalence of mental health was observed during the post-pandemic period compared to the outbreak period, including 7-day depression, 7-day anxiety, 30-day depression, and 30-day anxiety (all with P < 0.001). Female and patients with ≥2 comorbidities appeared to be more susceptible to postoperative depression and anxiety during the pandemic. LIMITATION: The absence of data from the early days of the COVID-19 outbreak. CONCLUSIONS: This study analyzed the prevalence of depression and anxiety in elderly non-cardiac patients during and after the COVID-19 pandemic, focusing on dimensions such as severity, risk-areas, gender, and comorbidity. Our findings revealed a significant decrease in the prevalence of depression and anxiety in elderly surgery patients during the post-pandemic period.

Improved Optimization of a Coextrusion Die with a Complex Geometry Using the Coupling Inverse Design Method.

The main challenge in a polymer coextrusion process is to have a good die design prior to the process, which can minimize the geometric errors that are caused by extrusion swell and interface motion. For this purpose, a coupling method of optimization and inverse design for a coextrusion die was studied for a medical striped catheter. In the study, the main material was thermoplastic polyurethane (TPU), and the auxiliary material was TPU filled with 30 wt% barium sulfate. An overall optimization design method was used to optimize the geometry of the extrusion die channel for the striped catheter, which had a complex geometry. In the global optimization process, the local inverse design method was used to design the inlet of the auxiliary material. The non-linear programming by quadratic Lagrangian (NLPQL) algorithm was used to obtain the optimal geometric solution of the coextrusion die runner. The experimental verification results showed that the coupling method for coextrusion die design improved the design efficiency of the coextrusion die remarkably. The value of the objective function, which was used to measure the geometric error of the product, was reduced by 72.3% compared with the initial die design.

Prognostic value of 11-factor modified frailty index in postoperative adverse outcomes of elderly gastric cancer patients in China.

BACKGROUND: Preoperative evaluation of frailty is limited to a few surgical procedures. However, the evaluation in Chinese elderly gastric cancer (GC) patients remains blank. AIM: To validate and estimate the prognostic value of the 11-index modified frailty index (mFI-11) for predicting postoperative anastomotic fistula, intensive care unit (ICU) admission, and long-term survival in elderly patients (over 65 years of age) undergoing radical GC. METHODS: This study was a retrospective cohort study which included patients who underwent elective gastrectomy with D2 Lymph node dissection between April 1, 2017 and April 1, 2019. The primary outcome was 1-year all-cause mortality. The secondary outcomes were admission to ICU, anastomotic fistula, and 6-mo mortality. Patients were divided into two groups according to the optimal grouping cutoff of 0.27 points from previous studies: High risk of frailty marked as mFI-11High and low risk of frailty marked as mFI-11Low. Survival curves between the two groups were compared, and univariate and multivariate regression analyses were performed to explore the relationship between preoperative frailty and postoperative complications in elderly patients undergoing radical GC. The discrimination ability of the mFI-11, prognostic nutritional index, and tumor-node-metastasis pathological stage to identify adverse postoperative outcomes was assessed by calculating the area under the receiver operating characteristic (ROC) curve. RESULTS: A total of 1003 patients were included, of which 13.86% (139/1003) were defined as having mFI-11High and 86.14% (864/1003) as having mFI-11Low. By comparing the incidence of postoperative complications in the two groups of patients, it was found that mFI-11High patients had higher rates of 1-year postoperative mortality, admission to ICU, anastomotic fistula, and 6-mo mortality than the mFI-11Low group (18.0% vs 8.9%, P = 0.001; 31.7% vs 14.7%, P < 0.001; 7.9% vs 2.8%, P < 0.001; and 12.2% vs 3.6%, P < 0.001). Multivariate analysis revealed mFI-11 as an independent predictive indicator for postoperative outcome [1-year postoperative mortality: Adjusted odds ratio (aOR) = 4.432, 95% confidence interval (95%CI): 2.599-6.343, P = 0.003; admission to ICU: aOR = 2.058, 95%CI: 1.188-3.563, P = 0.010; anastomotic fistula: aOR = 2.852, 95%CI: 1.357-5.994, P = 0.006; 6-mo mortality: aOR = 2.438, 95%CI: 1.075-5.484, P = 0.033]. mFI-11 showed better prognostic efficacy in predicting 1-year postoperative mortality [area under the ROC curve (AUROC): 0.731], admission to ICU (AUROC: 0.776), anastomotic fistula (AUROC: 0.877), and 6-mo mortality (AUROC: 0.759). CONCLUSION: Frailty as measured by mFI-11 could provide prognostic information for 1-year postoperative mortality, admission to ICU, anastomotic fistula, and 6-mo mortality in patients over 65 years old undergoing radical GC.

Therapeutic Effects of Huazhuojiedu Decoction on Precancerous Lesions of Gastric Cancer by Regulating Mitophagy.

This research aims to explore the therapeutic effect and potential mechanisms of Huazhuojiedu decoction (HZJD) for alleviating precancerous lesions of gastric cancer (PLGC) both in vivo and in vitro. HZJD is a traditional Chinese herbal formula consisting of 11 herbs. Sprague-Dawley (SD) rats were randomly divided into four subgroups: control group, model group, positive drug group, and HZJD group. Hematoxylin-eosin (H&E) staining, high iron diamine-alcian blue (HID-AB) staining, alcian blue-periodic acid Schiff (AB-PAS) staining, immunohistochemistry, immunofluorescence, RT-qPCR, and Western blot assays were performed after 10 weeks of HZJD treatment. In vitro, the cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect cell proliferation. RT-qPCR and Western blot assays were performed to evaluate mitophagy levels. The results indicated that HZJD could retard the pathological progression in PLGC rats and reduce PLGC cell proliferation. Treatment with HZJD significantly increased the mRNA and protein expression levels of Sirt3, Foxo3a, Parkin, and LC3 II/I, while decreasing the mRNA and protein expression levels of p62 and Tomm20. HZJD was found to have the ability to reverse the decline in mitophagy activity both in vivo and in vitro. In conclusion, the study assessed the impact of HZJD and provided evidence regarding its potential molecular mechanism.

Antitumor effect of luteolin proven by patient-derived organoids of gastric cancer.

Luteolin (Lut) has been shown to inhibit gastric cancer (GC); however, its efficacy compared to other clinical drugs has not been examined in human samples. This study aimed to elucidate the antitumor activity of Lut in GC patient-derived organoids (PDOs). PDOs were established from GC cancer tissues, and the characterization of tissues and PDOs was performed using whole-exome sequencing. Drug sensitivity tests were performed by treating PDOs with Lut, norcantharidin (NCTD), and carboplatin (CP). RNA sequencing of PDOs was performed to elucidate the antitumor mechanism of Lut, which was further verified in three GC cell lines. Eleven PDOs were successfully constructed, and were highly consistent with the pathophysiology and genetic changes in the corresponding tumors. The IC50s of Lut, NCTD, and CP of PDOs were 27.19, 23.9, and 37.87 µM, respectively. Lut treatment upregulated FOXO3, DUSP1, and CDKN1A expression and downregulated IL1R1 and FGFR4 expression in GC cell lines, which was consistent with the results of PDOs. We demonstrate that Lut exerted stronger antitumor effects than CP, but a similar effect to that of NCTD, which was obtained in an in vitro PDO system. Additionally, Lut exerted varying degrees of antitumor effects against the PDOs, thereby indicating that PDO may be a useful preclinical drug screening tool for personalized treatment.

Visible-light-mediated α-amino alkylation of ketimines and aldimines for the synthesis of 1,2-diamines.

A visible-light-mediated protocol to prepare 1,2-diamines has been successfully explored based on the photoredox/Brønsted acid co-catalyzed α-amino alkylations of imines with tertiary amines. Both ketimines and aldimines are applicable to this transformation. Various 1,2-diamines with different functional groups were produced in moderate to excellent yields. Moreover, this approach could be performed on a gram scale, showing its practicality.

Visible light-mediated three-component functionalization of olefins with sulfoxyimidoylsulfonium salt for the synthesis of ß-amino alcohols and amino ethers.

A new strategy involving three-component functionalization of olefins with sulfoxyimidoylsulfonium salt and a nucleophilic reagent for the synthesis of ß-amino alcohols and ß-amino ethers by photoredox catalysis was developed. The sulfoxyimidoylsulfonium salt is important and serves as the N-centred radical precursor. ß-Amino alcohols and ß-amino ethers bearing various functional groups are synthesized in good yields under mild conditions. Furthermore, the advantages of this strategy are greater safety, no additives, and easy to obtain raw materials.