Light-induced ß-hydroxy sulfone synthesis in DNA-encoded libraries.

We here describe a visible-light photooxidation of sulfinate salts with common alkenes to yield ß-hydroxy sulfones on DNA. This process demonstrates a broad substrate compatibility and achieves conversion rates ranging from moderate to excellent. Most importantly, it presents a straightforward, efficient, and metal-free approach for synthesizing Csp3-rich DNA-encoded libraries.

Evolutionary game analysis of factors influencing green innovation in Enterprises under environmental governance constraints.

The key to controlling environmental pollution is to promote green innovation in relevant enterprises and achieve a healthy development of the environmental governance system. This paper constructs a tripartite evolutionary game model of environmental protection enterprises, polluting enterprises, and governments, and conducts in-depth research on the influencing factors that promote green innovation in two types of enterprises. MATLAB software is used to analyze the impact of different degrees of influencing variables on system evolution. It has found that (1) increasing the intensity of environmental governance and the level of innovation subsidies by the government can effectively promote green innovation in both types of enterprises. (2) The varying degrees of innovation compensation from polluting enterprises to environmental protection enterprises have a significant impact on system evolution. (3) The initial intention and population size of two types of enterprise entities will have a significant impact on system evolution. In the initial state, subjects with more green innovation are less willing to change their strategies during the evolution process, while the willingness of the other party to green innovation will be suppressed.

Circulating ghrelin levels in patients with gastric cancer: a systematic review and meta-analysis.

Background: Ghrelin plays a critical role in regulating energy metabolism and homeostasis. The association between circulating ghrelin levels and gastric cancer has not been systematically analyzed. Objective: This work explored the association between circulating ghrelin levels and gastric cancer. Methods: The literature search for relevant articles published until November 2022 was performed using PubMed, Cochrane Library, EMBASE, and Web of Science with the keywords "ghrelin" and "gastric cancer". Standardized mean differences (SMD) with 95% confidence intervals were used to measure the effectiveness. We assessed pooled data by use of a random-effects model. Results: Of 5,302 identified studies, nine were included (N=3,196 participants). Circulating ghrelin levels were lower in gastric cancer patients (SMD=-0.255, 95%CI: -0.528 to 0.017, P < 0.00001), but with high heterogeneity (I2 = 88.8%). Conclusion: The circulating ghrelin levels in patients with gastric cancer were lower than in controls. However, there was heterogeneity among results; therefore, studies with larger sample sizes are recommended.

The Expression Pattern of Ferroptosis-Related Genes in Colon Adenocarcinoma: Highly Correlated to Tumor Microenvironment Characteristics.

In the latest literatures, ferroptosis caused by T cells in cancerous cells provided new insights of improving curative effect of the PD-1/PD-L1 antibody. The microenvironment on which tumor cells develop and survive was also emphasized as its crucial role in tumor occurrence, development, metastasis and immune escape. Thus, the interaction of ferroptosis related genes and tumor microenvironment (TME) was urgently be detected in a comprehensive perspective. We comprehensively evaluated the transcriptional feature of ferroptosis related genes in colon adenocarcinoma (COAD), and systematically associated these ferroptosis subtypes with DNA damage repair (DDR) and TME characteristics. We found two unique patterns of ferroptosis characterized by distinct biological pathways activation. We also demonstrated that FRG score constructed based on ferroptosis subtypes has a significant correlation with prognosis of colon cancer and could act as an independent prognostic biomarker for predicting patients' survival. The higher immune infiltrating level, immune functional pathways activation was observed in the high FRG score group. Furthermore, these results were verified by an independent external GEO cohort. This work revealed ferroptosis was highly associated with TME complexity and diversity. A novel ferroptosis subtypes related gene scoring system can be used for prognostic prediction in COAD. Targeting ferroptosis may be a therapeutic alternative for COAD.

Zelkovamycins B-E, Cyclic Octapeptides Containing Rare Amino Acid Residues from an Endophytic Kitasatospora sp.

Four unusual cyclopeptides, zelkovamycins B-E (1-4), were isolated from an endophytic Kitasatospora sp. Zelkovamycin B was featured by an unprecedented 3-methyl-5-hydroxypyrrolidine-2,4-dione ring system linked to the cyclopeptide skeleton. Their structures and full configurations were established by spectroscopic analysis, Marfey's method, and NMR calculations. A plausible biosynthetic pathway for zelkovamycins was proposed based on gene cluster analysis. Zelkovamycin E displayed potent inhibitory activity against H1N1 influenza A virus.

Apatinib combined with paclitaxel-based chemotherapy in patients with taxane-resistant advanced gastric cancer: a single-arm exploratory study.

BACKGROUND: Apatinib combined with chemotherapy might be effective and safe for the management of advanced gastric cancer, but the available data are limited. To investigate the efficacy and safety of apatinib in combination with paclitaxel (PTX) alone or POF (PTX, oxaliplatin, and 5-fluorouracil) in patients with taxane-resistant advanced gastric cancer. METHODS: Patients with taxane-resistant advanced gastric cancer were enrolled in the single-center, open-labeled, single-arm, exploratory study (ClinicalTrials.gov #NCT02697838). Apatinib was administered at 850 mg po in combination with weekly PTX or the POF regimen. The primary endpoint was the objective response rate (ORR). The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), the time to tumor progression (TTP), and safety. RESULTS: Twenty participants were recruited from 08/2016 to 01/2018. The duration of the study treatment was 2.07 (0.03-16.2) months. The median follow-up was 24.8 (0.3-26.0) months. The reasons for termination of treatment were disease progression (n=6), adverse events (AEs) (n=5), and patients' will (n=9). The ORR was 11.1% (95% CI: 1.4-34.7%) and the DCR was 77.8% (95% CI: 52.4-93.6%). The median PFS was 3.5 (95% CI: 1.9-5.1) months, the median OS was 4.7 (95% CI: 2.0-7.3) months, and the median TTP was 4.2 (95% CI: 0.562-7.838) months. All 20 (100%) patients had AEs, 17 (85%) had apatinib treatment-emergent AEs (TEAEs), and 18 (90%) had chemotherapy TEAEs. The main grade 3-4 TEAEs were neutropenia, leukopenia, hypertension, and anemia. CONCLUSIONS: This preliminary study suggests that apatinib combined with PTX or POF might be effective and tolerable in patients with chemotherapy-refractory gastric cancer. Studies are necessary to confirm the results. TRIAL REGISTRATION: ClinicalTrials.gov #NCT02697838.

Intelligent optofluidic analysis for ultrafast single bacterium profiling of cellulose production and morphology.

Bacterial cellulose (BC), a renewable type of cellulose, has been used in the manufacture of foods, cosmetics, and biomedical products. To produce BC, a high-throughput single-bacterium measurement is necessary to identify the functional bacteria that can produce BC with sufficient amount and desirable morphology. In this study, a continuous-flow intelligent optofluidic device was developed to enable high-throughput single-bacterium profiling of BC. Single bacteria were incubated in agarose hydrogel particles to produce BC with varied densities and structures. An intelligent convolutional neural network (CNN) computational method was developed to analyze the scattering patterns of BC. The BC production and morphology were determined with a throughput of ∼35 bacteria per second. A total of ∼105 single-bacterium BC samples were characterized within 3 hours. The high flexibility of this approach facilitates high-throughput comprehensive single-cell production analysis for a range of applications in engineering biology.

Production of Hollow Bacterial Cellulose Microspheres Using Microfluidics to Form an Injectable Porous Scaffold for Wound Healing.

Bacterial cellulose (BC) is a biocompatible material with high purity and robust mechanical strength used to fabricate desirable scaffolds for 3D cell culture and wound healing. However, the chemical resistance of BC and its insolubility in the majority of solutions make it difficult to manipulate using standard chemical methods. In this study, a microfluidic process is developed to produce hollow BC microspheres with desirable internal structures and morphology. Microfluidics is used to generate a core-shell structured microparticle with an alginate core and agarose shell as a template to encapsulate Gluconacetobacter xylinus for long-term static culture. G. xylinus then secretes BC, which becomes entangled within the shell of the structured hydrogel microparticles and forms BC microspheres. The removal of the hydrogel template via thermal-chemical treatments yields robust BC microspheres exhibiting a hollow morphology. These hollow microspheres spontaneously assemble as functional units to form a novel injectable scaffold. In vitro, a highly porous scaffold is created to enable effective 3D cell culture with a high cell proliferation rate and better depth distribution. In vivo, this injectable scaffold facilitates tissue regeneration, resulting in rapid wound-healing in a Sprague Dawley rat skin model.

Real-time measurement of thrombin generation using continuous droplet microfluidics.

Thrombin, which has the leading role in the blood coagulation cascade, is an important biomarker in hemostasis and cardiovascular disease (CVD) development. In this study, a measurement system capable of continuously monitoring individual thrombin generation using droplet microfluidic technology is manipulated. The thrombin generation assay based on fluogenic substrate is performed within the droplets and the thrombin generation curve of plasma sample activated by tissue factor is measured in real-time to reflect the sample conditions dynamically. The injection of the inhibitor of thrombin generation is developed to assay the inhibited curve which relates to thrombin self-inhibition in biological systems. This microfluidic system is integrated with the microdialysis probe, which is useful to connect to the living animals for future in vivo real time thrombin measurements for rapid CVD diagnosis.