Thrombospondin 1 and Reelin act through Vldlr to regulate cardiac growth and repair.

Adult mammalian cardiomyocytes have minimal cell cycle capacity, which leads to poor regeneration after cardiac injury such as myocardial infarction. Many positive regulators of cardiomyocyte cell cycle and cardioprotective signals have been identified, but extracellular signals that suppress cardiomyocyte proliferation are poorly understood. We profiled receptors enriched in postnatal cardiomyocytes, and found that very-low-density-lipoprotein receptor (Vldlr) inhibits neonatal cardiomyocyte cell cycle. Paradoxically, Reelin, the well-known Vldlr ligand, expressed in cardiac Schwann cells and lymphatic endothelial cells, promotes neonatal cardiomyocyte proliferation. Thrombospondin1 (TSP-1), another ligand of Vldlr highly expressed in adult heart, was then found to inhibit cardiomyocyte proliferation through Vldlr, and may contribute to Vldlr's overall repression on proliferation. Mechanistically, Rac1 and subsequent Yap phosphorylation and nucleus translocation mediate the regulation of the cardiomyocyte cell cycle by TSP-1/Reelin-Vldlr signaling. Importantly, Reln mutant neonatal mice displayed impaired cardiomyocyte proliferation and cardiac regeneration after apical resection, while cardiac-specific Thbs1 deletion and cardiomyocyte-specific Vldlr deletion promote cardiomyocyte proliferation and are cardioprotective after myocardial infarction. Our results identified a novel role of Vldlr in consolidating extracellular signals to regulate cardiomyocyte cell cycle activity and survival, and the overall suppressive TSP-1-Vldlr signal may contribute to the poor cardiac repair capacity of adult mammals.

Clostridium aquiflavi sp. nov., isolated from yellow water of Nongxiangxing baijiu in the Yibin region of China.

A Gram-stain-positive, strictly anaerobic, endospore-forming and rod-shaped (0.6-0.8×2.7-13.1 µm) bacterium, designated as 5 N-1T, was isolated from a yellow water sample collected from the manufacturing process of Nongxiangxing baijiu in the Yibin region of Sichuan, PR China. Growth occurred at 15-40 °C (optimum growth at 37 °C), at pH 6.0-9.0 (optimum growth at pH 7.0) and in NaCl concentrations of 0-1 % (w/v) and ethanol concentrations of 0-2 % (v/v). The major fatty acids in strain 5 N-1T were C16 : 0, C18 : 0 and C14 : 0. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, four unidentified aminophospholipids and one unidentified lipid. Phylogenetic analysis of its 16S rRNA gene sequence indicated that strain 5 N-1T was most closely related to Clostridium weizhouense YB-6T (97.70 %) and Clostridium uliginosum DSM 12992T (97.56 %). The average nucleotide identity and digital DNA‒DNA hybridization values between strain 5 N-1T and the above two type strains were 80.89 and 80.05 % and 25.80 and 25.30 %, respectively, which were all below the species thresholds. The genome size of strain 5 N-1T was 3.5 Mbp and the DNA G+C content was 27.5 mol%. Based on the results of phenotypic and genotypic analyses, strain 5 N-1T represents a novel species of the genus Clostridium, for which the name Clostridium aquiflavi sp. nov. is proposed. The type strain is Clostridium aquiflavi 5 N-1T (=CICC 24886T=JCM 35355T).

Study on microbial diversity of washing machines.

Health and environmental protection are the development trend of household appliances, coupled with the impact of the COVID-19 epidemic in the past few years. Consumers have unprecedented concerns and expectations about the sterilization and disinfection functions of household appliances. As a washing and nursing equipment for household clothes, the anti-bacterial technology of washing machine has developed rapidly. The new models of washing machines in the market have basically added the function of sterilization. In order to thoroughly solve the problem of sterilization and bacteriostasis of washing machines from the source, the distribution of microbial contamination in washing machines should be fully investigated. At present, there is almost no systematic study on the microbial community structure in washing machines in China. Therefore, the purpose of this study is to analyze the bacterial community structure in Chinese household washing machines. To explore the key factors affecting the bacterial community structure of washing machines. Bacterial communities were comprehensively analyzed by high throughput sequencing. Using chao and shannon indexes as indicators, one-way ANOVA was used to explore the key factors affecting the bacterial community structure of washing machines. A total of 2,882,778 tags and 21,265 OTUs from 522 genera were sequenced from 56 washing machine samples. Genus Mycobacterium, Pseudomonas, Brevundimonas, Sphingomonas, Sphingobium, Enhydrobacter, Methylobacterium, Pseudoxanthomonas, Stenotrophomonas and Sphingopyxis were the top ten bacteria genera in abundance. The effects of sources, types, frequency of utilization, sampling locations and service life of washing machines on bacterial diversity in washing machine were systematically analyzed. The statistical analysis showed that service life was an important factor affecting bacterial diversity in washing machine. Our study lays a foundation for directional screening of characteristic microorganisms with targeted characters including malodor-producing, fouling, pathogenic and stress-resistance, the antibacterial evaluation, metabolic mechanism of key characteristic microorganisms as well as antibacterial materials development. At present, the sterilization technology of washing machines has not been fully in combination with the distribution survey of microorganisms in washing machines. According to the specific microorganism distribution condition of the washing machine, the key distribution positions and the types of specific microorganisms contained in different positions, conduct more targeted sterilization treatment. This will help to completely solve the problem of microbial growth in washing machines from the source.

Development of a single nucleotide polymorphism-based strain-identified method for Streptococcus thermophilus CICC 6038 and Lactobacillus delbrueckii ssp. bulgaricus CICC 6047 using pan-genomics analysis.

The health benefits conferred by probiotics is specific to individual probiotic strains, highlighting the importance of identifying specific strains for research and production purposes. Streptococcus thermophilus CICC 6038 and Lactobacillus delbrueckii ssp. bulgaricus CICC 6047 are exceedingly valuable for commercial use with an excellent mixed-culture fermentation. To differentiate these 2 strains from other S. thermophilus and L. delbrueckii ssp. bulgaricus, a specific, sensitive, accurate, rapid, convenient, and cost-effective method is required. In this study, we conducted a pan-genome analysis of S. thermophilus and L. delbrueckii ssp. bulgaricus to identify species-specific core genes, along with strain-specific SNPs. These genes were used to develop suitable PCR primers, and the conformity of sequence length and unique SNPs was confirmed by sequencing for qualitative identification at the strain level. The results demonstrated that SNPs analysis of PCR products derived from these primers could distinguish CICC 6038 and CICC 6047 accurately and reproducibly from the other strains of S. thermophilus and L. delbrueckii ssp. bulgaricus, respectively. The strain-specific PCR method based on SNPs herein is universally applicable for probiotics identification. It offers valuable insights into identifying probiotics at the strain level that is fit-for-purpose in quality control and compliance assessment of commercial dairy products.

Fermentation characteristics and postacidification of yogurt by Streptococcus thermophilus CICC 6038 and Lactobacillus delbrueckii ssp. bulgaricus CICC 6047 at optimal inoculum ratio.

This study aimed to investigate the symbiosis between Streptococcus thermophilus CICC 6038 and Lactobacillus delbrueckii ssp. bulgaricus CICC 6047. In addition, the effect of their different inoculum ratios was determined, and comparison experiments of fermentation characteristics and storage stability of milk fermented by their monocultures and cocultures at optimal inoculum ratio were performed. We found the time to obtain pH 4.6 and ΔpH during storage varied among 6 inoculum ratios (1:1, 2:1, 10:1, 19:1, 50:1, 100:1). By the statistical model to evaluate the optimal ratio, the ratio of 19:1 was selected, which exhibited high acidification rate and low postacidification with pH values remaining between 4.2 and 4.4 after a 50-d storage. Among the 3 groups included in our analyses (i.e., the monocultures of S. thermophilus CICC 6038 [St] and Lb. bulgaricus CICC 6047 [Lb] and their cocultures [St+Lb] at 19:1), the coculture group showed higher acidification activity, improved rheological properties, richer typical volatile compounds, more desirable sensor quality after the fermentation process than the other 2 groups. However, the continuous accumulation of acetic acid during storage showed that acetic acid was more highly correlated with postacidification than d-lactic acid for the Lb group and St+Lb group. Our study emphasized the importance of selecting an appropriate bacterial consortium at the optimal inoculum ratio to achieve favorable fermentation performance and enhanced postacidification stability during storage.

Fermentation Characteristics of Fermented Milk with Streptococcus thermophilus CICC 6063 and Lactobacillus helveticus CICC 6064 and Volatile Compound Dynamic Profiles during Fermentation and Storage.

The lactic acid bacteria Streptococcus thermophilus and Lactobacillus helveticus are commonly used as starter cultures in dairy product production. This study aimed to investigate the characteristics of fermented milk using different ratios of these strains and analyze the changes in volatile compounds during fermentation and storage. A 10:1 ratio of Streptococcus thermophilus CICC 6063 to Lactobacillus helveticus CICC 6064 showed optimal fermentation time (4.2 h), viable cell count (9.64 log10 colony-forming units/mL), and sensory evaluation score (79.1 points). In total, 56 volatile compounds were identified and quantified by solid-phase microextraction and gas chromatography-mass spectrometry (SPME-GC-MS), including aldehydes, ketones, acids, alcohols, esters, and others. Among these, according to VIP analysis, 2,3-butanedione, acetoin, 2,3-pentanedione, hexanoic acid, acetic acid, acetaldehyde, and butanoic acid were identified as discriminatory volatile metabolites for distinguishing between different time points. Throughout the fermentation and storage process, the levels of 2,3-pentanedione and acetoin exhibited synergistic dynamics. These findings enhance our understanding of the chemical and molecular characteristics of milk fermented with Streptococcus thermophilus and Lactobacillus helveticus, providing a basis for improving the flavor and odor of dairy products during fermentation and storage.

CO2 Photoactivation Study of Adenine Nucleobase: Role of Hydrogen-Bonding Traction.

The discovery and in-depth study of non-biocatalytic applications of active biomolecules are essential for the development of biomimicry. Here, the effect of intermolecular hydrogen-bonding traction on the CO2 photoactivation performance of adenine nucleobase by means of an adenine-containing model system (AMOF-1-4) is uncovered. Remarkably, the hydrogen-bonding schemes around adenines are regularly altered with the increase in the alkyl (methyl, ethyl, isopropyl, and tert-butyl) electron-donating capacity of the coordinated aliphatic carboxylic acids, and thus, lead to a stepwise improvement in CO2 photoreduction activity. Density functional theory calculations demonstrate that strong intermolecular hydrogen-bonding traction surrounding adenine can obviously increase the adenine-CO2 interaction energy and, therefore, result in a smoother CO2 activation process. Significantly, this work also provides new inspiration for expanding the application of adenine to more small-molecule catalytic reactions.

An artificial intelligence-based ecological index for prognostic evaluation of colorectal cancer.

BACKGROUND AND OBJECTIVE: In the tumor microenvironment (TME), the dynamic interaction between tumor cells and immune cells plays a critical role in predicting the prognosis of colorectal cancer. This study introduces a novel approach based on artificial intelligence (AI) and immunohistochemistry (IHC)-stained whole-slide images (WSIs) of colorectal cancer (CRC) patients to quantitatively assess the spatial associations between tumor cells and immune cells. To achieve this, we employ the Morisita-Horn ecological index (Mor-index), which allows for a comprehensive analysis of the spatial distribution patterns between tumor cells and immune cells within the TME. MATERIALS AND METHODS: In this study, we employed a combination of deep learning technology and traditional computer segmentation methods to accurately segment the tumor nuclei, immune nuclei, and stroma nuclei within the tumor regions of IHC-stained WSIs. The Mor-index was used to assess the spatial association between tumor cells and immune cells in TME of CRC patients by obtaining the results of cell nuclei segmentation. A discovery cohort (N = 432) and validation cohort (N = 137) were used to evaluate the prognostic value of the Mor-index for overall survival (OS). RESULTS: The efficacy of our method was demonstrated through experiments conducted on two datasets comprising a total of 569 patients. Compared to other studies, our method is not only superior to the QuPath tool but also produces better segmentation results with an accuracy of 0.85. Mor-index was quantified automatically by our method. Survival analysis indicated that the higher Mor-index correlated with better OS in the discovery cohorts (HR for high vs. low 0.49, 95% CI 0.27-0.77, P = 0.0014) and validation cohort (0.21, 0.10-0.46, < 0.0001). CONCLUSION: This study provided a novel AI-based approach to segmenting various nuclei in the TME. The Mor-index can reflect the immune status of CRC patients and is associated with favorable survival. Thus, Mor-index can potentially make a significant role in aiding clinical prognosis and decision-making.

Kingella pumchi sp. nov., an organism isolated from human vertebral puncture tissue.

A Gram-negative, non-motile rod and strictly aerobic bacterium, designated as 18B16333T, was isolated from vertebral puncture tissue of a patient at Peking union medical college hospital in China. Growth occurred in NaCl concentrations of 0-1% (w/v) (optimum growth at 0% NaCl), at temperatures of 25-40 °C (optimum growth at 37 °C) and at pH 6.0-9.0 (optimum growth at pH 8.0). Diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine were the predominant polar lipids, and the major fatty acids were C16:0, C18:1 ω7c/C18:1 ω6c and C16:1 ω7c/C16:1 ω6c. Phylogenetic analysis based on 16S rRNA gene sequence comparisons indicated that strain 18B16333T was most closely related to Kingella potus CCUG 49773 T (97.3%, 16S rRNA gene sequence identity) and Neisseria bacilliformis CCUG 50858 T (96.8%). The ANI values between strain 18B16333T and the type strains K. potus CCUG 49773 T, N. bacilliformis CCUG 50858 T, Kingella kingae CCUG 352 T and Neisseria gonorrhoeae CCUG 26876 T were 77.3%, 79.1%, 72.1% and 75.4%, respectively. The dDDH values between strain 18B16333T and the four reference strains mentioned above were 24.8%, 26.9%, 24.2% and 20.7%. Further core gene analysis distinctively clustered strain 18B16333T with four Kingella species but not with Neisseria species. Based on the phenotypic, chemotaxonomic, and phylogenetic properties, strain 18B16333T represents a novel species of the genus Kingella, for which the name Kingella pumchi sp. nov. is proposed. The type strain is Kingella pumchi 18B16333T (= CICC 24913 T = CCUG 75125 T).

gcType: a high-quality type strain genome database for microbial phylogenetic and functional research.

Taxonomic and functional research of microorganisms has increasingly relied upon genome-based data and methods. As the depository of the Global Catalogue of Microorganisms (GCM) 10K prokaryotic type strain sequencing project, Global Catalogue of Type Strain (gcType) has published 1049 type strain genomes sequenced by the GCM 10K project which are preserved in global culture collections with a valid published status. Additionally, the information provided through gcType includes >12 000 publicly available type strain genome sequences from GenBank incorporated using quality control criteria and standard data annotation pipelines to form a high-quality reference database. This database integrates type strain sequences with their phenotypic information to facilitate phenotypic and genotypic analyses. Multiple formats of cross-genome searches and interactive interfaces have allowed extensive exploration of the database's resources. In this study, we describe web-based data analysis pipelines for genomic analyses and genome-based taxonomy, which could serve as a one-stop platform for the identification of prokaryotic species. The number of type strain genomes that are published will continue to increase as the GCM 10K project increases its collaboration with culture collections worldwide. Data of this project is shared with the International Nucleotide Sequence Database Collaboration. Access to gcType is free at http://gctype.wdcm.org/.

Structural Evolution of Giant Polyoxometalate: From "Keplerate" to "Lantern" Type Mo132 for Improved Oxidation Catalysis.

Structural variants of high-nuclearity clusters are extremely important for their modular assembly study and functional expansion, yet the synthesis of such giant structural variants remains a great challenge. Herein, we prepared a lantern-type giant polymolybdate cluster (L-Mo132 ) containing equal metal nuclearity with the famous Keplerate type Mo132 (K-Mo132 ). The skeleton of L-Mo132 features a rare truncated rhombic triacontrahedron, which is totally different with the truncated icosahedral K-Mo132 . To the best of our knowledge, this is the first time to observe such structural variants in high-nuclearity cluster built up of more than 100 metal atoms. Scanning transmission electron microscopy reveals that L-Mo132 has good stability. More importantly, because the pentagonal [Mo6 O27 ]n- building blocks in L-Mo132 are concave instead of convex in the outer face, it contains multiple terminal coordinated water molecules on its outer surface, which make it expose more active metal sites to display superior phenol oxidation performance, which is more higher than that of K-Mo132 coordinated in M=O bonds on the outer surface.

Unfavourable intrauterine environment contributes to abnormal gut microbiome and metabolome in twins.

OBJECTIVE: Fetal growth restriction (FGR) is a devastating pregnancy complication that increases the risk of perinatal mortality and morbidity. This study aims to determine the combined and relative effects of genetic and intrauterine environments on neonatal microbial communities and to explore selective FGR-induced gut microbiota disruption, metabolic profile disturbances and possible outcomes. DESIGN: We profiled and compared the gut microbial colonisation of 150 pairs of twin neonates who were classified into four groups based on their chorionicity and discordance of fetal birth weight. Gut microbiota dysbiosis and faecal metabolic alterations were determined by 16S ribosomal RNA and metagenomic sequencing and metabolomics, and the long-term effects were explored by surveys of physical and neurocognitive development conducted after 2~3 years of follow-up. RESULTS: Adverse intrauterine environmental factors related to selective FGR dominate genetics in their effects of elevating bacterial diversity and altering the composition of early-life gut microbiota, and this effect is positively related to the severity of selective FGR in twins. The influence of genetic factors on gut microbes diminishes in the context of selective FGR. Gut microbiota dysbiosis in twin neonates with selective FGR and faecal metabolic alterations features decreased abundances of Enterococcus and Acinetobacter and downregulated methionine and cysteine levels. Correlation analysis indicates that the faecal cysteine level in early life is positively correlated with the physical and neurocognitive development of infants. CONCLUSION: Dysbiotic microbiota profiles and pronounced metabolic alterations are associated with selective FGR affected by adverse intrauterine environments, emphasising the possible effects of dysbiosis on long-term neurobehavioural development.

PLK inhibitors identified by high content phenotypic screening promote maturation of human PSC-derived cardiomyocytes.

Human pluripotent stem cells-derived cardiomyocytes (hPSC-CMs) provide an unlimited source of human cardiomyocytes for disease modeling, cell therapies, and other biomedical applications. However, hPSC-CMs remain developmentally immature which limits their suitability in translational applications. High Content Screening (HCS) is a powerful tool for identifying novel molecules and pathways regulating complex biological processes, but no HCS assay for hPSC-CM maturation has yet been reported. PCM1, a centriole satellite protein, is specifically restricted on nuclear envelope in mature cardiomyocytes. We developed a High Content Screen (HCS) based on PCM1 subcellular localization in hPSC-CMs to identify novel molecules promoting cardiomyocyte maturation, which identified 93 from 1693 compounds that enhance maturation of hPSC-CMs, including multiple PLK inhibitors. Volasertib and Centrinone, two PLK inhibitors, can enhance binucleation, and promote metabolic and electrophysiological maturation in hPSC-CMs. Furthermore, PI3K-AKT signaling pathway was found to be suppressed by PLK inhibitors, and VO-Ohpic, a PTEN inhibitor that activates AKT pathway, blunted the effect of PLK inhibitors on hPSC-CM maturation. In summary, our HCS assay found that PLK inhibitors can promote maturation of hPSC-CMs through suppressing AKT signaling pathway.

The Crohn's-like lymphoid reaction density: a new artificial intelligence quantified prognostic immune index in colon cancer.

BACKGROUND: The Crohn's-like lymphoid reaction (CLR) is manifested as peritumoral lymphocytes aggregation in colon cancer, which is a major component of the host immune response to cancer. However, the lack of a unified and objective CLR evaluation standard limits its clinical application. We, therefore, developed a deep learning model for the fully automated CLR density quantification on routine hematoxylin and eosin (HE)-stained whole-slide images (WSIs) and further investigated its prognostic validity for patient stratification. METHODS: The CLR density was calculated by using a deep learning method on HE-stained WSIs. A training (N = 279) and a validation (N = 194) cohorts were used to evaluate the prognostic value of CLR density for overall survival (OS). RESULT: The fully automated quantified CLR density was an independent prognostic factor, with high CLR density associated with increased OS in the discovery (HR 0.58, 95% CI 0.38-0.89, P = 0.012) and validation cohort (0.45, 0.23-0.88, 0.020). Integrating CLR density into a Cox model with other risk factors showed improved prognostic capability. CONCLUSION: We developed a new immune indicator (CLR density) quantified by a deep learning method to evaluate the lymphocytes aggregation in colon cancer. The CLR density was demonstrated its predictive value for OS in two independent cohorts. This approach allows for the objective and standardized quantification while reducing pathologists' workload. Therefore, this fully automated standardized method of CLR evaluation had potential clinical value.

Artificial intelligence for quantifying immune infiltrates interacting with stroma in colorectal cancer.

BACKGROUND: We proposed an artificial intelligence-based immune index, Deep-immune score, quantifying the infiltration of immune cells interacting with the tumor stroma in hematoxylin and eosin-stained whole-slide images of colorectal cancer. METHODS: A total of 1010 colorectal cancer patients from three centers were enrolled in this retrospective study, divided into a primary (N = 544) and a validation cohort (N = 466). We proposed the Deep-immune score, which reflected both tumor stroma proportion and the infiltration of immune cells in the stroma region. We further analyzed the correlation between the score and CD3+ T cells density in the stroma region using immunohistochemistry-stained whole-slide images. Survival analysis was performed using the Cox proportional hazard model, and the endpoint of the event was the overall survival. RESULT: Patients were classified into 4-level score groups (score 1-4). A high Deep-immune score was associated with a high level of CD3+ T cells infiltration in the stroma region. In the primary cohort, survival analysis showed a significant difference in 5-year survival rates between score 4 and score 1 groups: 87.4% vs. 58.2% (Hazard ratio for score 4 vs. score 1 0.27, 95% confidence interval 0.15-0.48, P < 0.001). Similar trends were observed in the validation cohort (89.8% vs. 67.0%; 0.31, 0.15-0.62, < 0.001). Stratified analysis showed that the Deep-immune score could distinguish high-risk and low-risk patients in stage II colorectal cancer (P = 0.018). CONCLUSION: The proposed Deep-immune score quantified by artificial intelligence can reflect the immune status of patients with colorectal cancer and is associate with favorable survival. This digital pathology-based finding might advocate change in risk stratification and consequent precision medicine.

Development and validation of a preoperative CT-based radiomic nomogram to predict pathology invasiveness in patients with a solitary pulmonary nodule: a machine learning approach, multicenter, diagnostic study.

OBJECTIVES: To develop and validate a preoperative CT-based nomogram combined with radiomic and clinical-radiological signatures to distinguish preinvasive lesions from pulmonary invasive lesions. METHODS: This was a retrospective, diagnostic study conducted from August 1, 2018, to May 1, 2020, at three centers. Patients with a solitary pulmonary nodule were enrolled in the GDPH center and were divided into two groups (7:3) randomly: development (n = 149) and internal validation (n = 54). The SYSMH center and the ZSLC Center formed an external validation cohort of 170 patients. The least absolute shrinkage and selection operator (LASSO) algorithm and logistic regression analysis were used to feature signatures and transform them into models. RESULTS: The study comprised 373 individuals from three independent centers (female: 225/373, 60.3%; median [IQR] age, 57.0 [48.0-65.0] years). The AUCs for the combined radiomic signature selected from the nodular area and the perinodular area were 0.93, 0.91, and 0.90 in the three cohorts. The nomogram combining the clinical and combined radiomic signatures could accurately predict interstitial invasion in patients with a solitary pulmonary nodule (AUC, 0.94, 0.90, 0.92) in the three cohorts, respectively. The radiomic nomogram outperformed any clinical or radiomic signature in terms of clinical predictive abilities, according to a decision curve analysis and the Akaike information criteria. CONCLUSIONS: This study demonstrated that a nomogram constructed by identified clinical-radiological signatures and combined radiomic signatures has the potential to precisely predict pathology invasiveness. KEY POINTS: • The radiomic signature from the perinodular area has the potential to predict pathology invasiveness of the solitary pulmonary nodule. • The new radiomic nomogram was useful in clinical decision-making associated with personalized surgical intervention and therapeutic regimen selection in patients with early-stage non-small-cell lung cancer.

Ferrocene-Functionalized Crystalline Biomimetic Catalysts for Efficient CO2 Photoreduction.

Photoreducing carbon dioxide (CO2) into highly valued chemicals or energy products has been recognized as one of the most promising proposals to degrade atmospheric CO2 concentration and achieve carbon neutrality. Adenine with a photosensitive amino group and aromatic nitrogen atom can strongly interact with CO2 and has been authenticated for its catalytic activity for the CO2 photoreduction reaction (CO2RR). Herein, two adenine-constructed crystalline biomimetic photocatalysts (Co2-AW and Co2-AF) were designed and synthesized to achieve CO2RR. Between them, Co2-AF displayed higher photocatalytic activity (225.8 µmol g-1 h-1) for CO2-to-HCOOH conversion than that of Co2-AW. It was found that the superior charge transfer capacity of the functional ferrocene group in Co2-AF is the primary reason to facilitate the photocatalytic performance efficiently. Additionally, this work also demonstrated the great potential of the ferrocene group as an electron donor and mediator in improving the photocatalytic activity of crystalline coordination catalysts.

Targeting cholesterol biosynthesis promotes anti-tumor immunity by inhibiting long noncoding RNA SNHG29-mediated YAP activation.

Anti-tumor immunity through checkpoint inhibitors, specifically anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) interaction, is a promising approach for cancer therapy. However, as early clinical trials indicate that colorectal cancers (CRCs) do not respond well to immune-checkpoint therapies, new effective immunotherapy approaches to CRC warrant further study. Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (CoA) reductase (HMGCR), the rate-limiting enzyme of the mevalonate (MVA) pathway for the cholesterol biosynthesis. However, little is known about the functions of simvastatin in the regulation of immune checkpoints or long noncoding RNA (lncRNA)-mediated immunoregulation in cancer. Here, we found that simvastatin inhibited PD-L1 expression and promoted anti-tumor immunity via suppressing the expression of lncRNA SNHG29. Interestingly, SNHG29 interacted with YAP and inhibited phosphorylation and ubiquitination-mediated protein degradation of YAP, thereby facilitating downregulation of PD-L1 transcriptionally. Patient-derived tumor xenograft (PDX) models and the clinicopathological analysis in samples from CRC patients further supported the role of the lncRNA SNHG29-mediated PD-L1 signaling axis in tumor microenvironment reprogramming. Collectively, our study uncovers simvastatin as a potential therapeutic drug for immunotherapy in CRC, which suppresses lncRNA SNHG29-mediated YAP activation and promotes anti-tumor immunity by inhibiting PD-L1 expression.

Genome-Based Analysis of Aspergillus niger Aggregate Species from China and Their Potential for Fumonisin B2 and Ochratoxin A Production.

Based on entire genome sequencing, this study focused on the classification of Aspergillus niger aggregation species and investigated their potential for fumonisin B2 (FB2) and ochratoxin A (OTA) production. In the current study, 22 strains were used, namely 17 A. niger strains, four A. welwitschiae strains, and one A. lacticoffeatus (a synonym of A. niger) strain. Traditional multigene phylogenetic analysis, average nucleotide identity analysis (ANI), and the whole-genome single-nucleotide polymorphism (SNP) analyses were used to reconfirm the taxonomic status of A. niger, A. welwitschiae, and A. lacticoffeatus. The ability of A. niger to produce FB2 and OTA on five culture substrates was determined, and the association between FB2 and OTA gene clusters and toxin-producing abilities was explored. The results revealed that the ANI method could distinguish A. niger from A. welwitschiae, with an ANI value of < 98%. The SNP-based phylogenetic analysis suggested that A. niger and A. welwitschiae were two independent phylogenetic species. The ANI, SNP, and multigene phylogenetic analysis supported previous findings that A. lacticoffeatus was a synonymous species of A. niger. Aspergillus niger strains exhibited the varied potential of producing FB2 and OTA on different culture media. The A. niger genome sequence analysis revealed no significant difference in fumonisin gene clusters between FB2-nonproducing isolates and FB2-producing isolates, and the integrity of the ochratoxin biosynthesis genes cluster was clearly associated with OTA production. In conclusion, gene sequencing can be useful in assessing A. niger's ability to produce OTA, but it cannot reliably predict its ability to produce FB2.

Inoculum size of co-fermentative culture affects the sensory quality and volatile metabolome of fermented milk over storage.

Lacticaseibacillus paracasei PC-01 is a probiotic candidate isolated from naturally fermented yak milk in Lhasa, Tibet, and it has been shown to possess excellent milk fermentation properties. This study used Lacticaseibacillus paracasei PC-01 as a co-fermentation strain to investigate the effect of inoculum size with a commercial starter in milk fermentation on the product flavor and profile of volatile metabolites over 28 d of cold storage. Lacticaseibacillus paracasei PC-01 was allowed to ferment in pasteurized milk with or without the commercial starter (YF-L904) at 42°C until the pH decreased to 4.5. The finished fermented milks were stored at 10°C for 28 d. Milk samples were taken at hour 0 (before fermentation) and then at d 1, 14, and 28 of cold storage. Different inoculum sizes of Lacticaseibacillus paracasei PC-01 had no significant effect on pH or titratable acidity during storage of fermented milk. Viable counts of strain PC-01 continued to increase during cold storage of the fermented milk. Generally, as storage of fermented milk proceeded, the overall sensory quality score decreased in all groups. However, the overall sensory scores of PC-01-M were generally higher than those of other groups, suggesting that a medium dose of Lacticaseibacillus paracasei PC-01 had the most obvious effect of slowing the decline in sensory quality of fermented milk during storage. Changes in sensory scores and consumer preferences were accompanied by increases in both the quantity and variety of key volatile metabolites in fermented milk during fermentation, post-ripening (d 1), and storage. Major differentially abundant metabolites, including acetaldehyde, methyl ketones, medium-chain and short-chain fatty acids, 2,3-butanedione, and acetoin, were enriched in fermented milks rated highly in the sensory evaluation. Our data confirmed that the inoculum size of co-fermentative culture affected the sensory quality and volatile metabolome of fermented milk over storage, and an optimal range of co-fermentative culture was titrated in this work.