Association of common maternal infections with birth outcomes: a multinational cohort study.

PURPOSE: It is unclear whether common maternal infections during pregnancy are risk factors for adverse birth outcomes. We assessed the association between self-reported infections during pregnancy with preterm birth and small-for-gestational-age (SGA) in an international cohort consortium. METHODS: Data on 120,507 pregnant women were obtained from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA. Self-reported common infections during pregnancy included influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections, cystitis, urinary tract infection, and the symptoms fever and diarrhoea. Birth outcomes included preterm birth, low birth weight and SGA. Associations between maternal infections and birth outcomes were first assessed using Poisson regression in each cohort and then pooled using random-effect meta-analysis. Risk ratios (RR) and 95% confidence intervals (CI) were calculated, adjusted for potential confounders. RESULTS: Vaginal infections (pooled RR, 1.10; 95% CI, 1.02-1.20) and urinary tract infections (pooled RR, 1.17; 95% CI, 1.09-1.26) during pregnancy were associated with higher risk of preterm birth. Similar associations with low birth weight were also observed for these two infections. Fever during pregnancy was associated with higher risk of SGA (pooled RR, 1.07; 95% CI, 1.02-1.12). No other significant associations were observed between maternal infections/symptoms and birth outcomes. CONCLUSION: Vaginal infections and urinary infections during pregnancy were associated with a small increased risk of preterm birth and low birth weight, whereas fever was associated with SGA. These findings require confirmation in future studies with laboratory-confirmed infection diagnosis.

10× single-cell sequencing revealed cellular composition heterogeneity in cardiac myxoma with malignant glandular properties.

Cardiac myxoma is the most common primary cardiac tumor in adults. The histogenesis and cellular composition of myxoma are still unclear. This study aims to reveal the role of myxoma cell components and their gene expression in tumor development. We obtained single living cells by enzymatic digestion of tissues from 4 cases of surgically resected cardiac myxoma. Of course, there was 1 case of glandular myxoma and 3 cases of nonglandular myxoma. Then, 10× single-cell sequencing was performed. We identified 12 types and 11 types of cell populations in glandular myxoma and nonglandular myxoma, respectively. Heterogeneous epithelial cells are the main components of glandular myxoma. The similarities and differences in T cells in both glandular and nonglandular myxoma were analyzed by KEGG and GO. The most important finding was that there was active communication between T cells and epithelial cells. These results clarify the possible tissue occurrence and heterogeneity of cardiac myxoma and provide a theoretical basis and guidance for clinical diagnosis and treatment.

3D Printed Multifunctional Biomimetic Bone Scaffold Combined with TP-Mg Nanoparticles for the Infectious Bone Defects Repair.

Infected bone defects are one of the most challenging problems in the treatment of bone defects due to the high antibiotic failure rate and the lack of ideal bone grafts. In this paper, inspired by clinical bone cement filling treatment, α-c phosphate (α-TCP) with self-curing properties is composited with ß-tricalcium phosphate (ß-TCP) and constructed a bionic cancellous bone scaffolding system α/ß-tricalcium phosphate (α/ß-TCP) by low-temperature 3D printing, and gelatin is preserved inside the scaffolds as an organic phase, and later loaded with a metal-polyphenol network structure of tea polyphenol-magnesium (TP-Mg) nanoparticles. The scaffolds mimic the structure and components of cancellous bone with high mechanical strength (>100 MPa) based on α-TCP self-curing properties through low-temperature 3D printing. Meanwhile, the scaffolds loaded with TP-Mg exhibit significant inhibition of Staphylococcus aureus (S.aureus) and promote the transition of macrophages from M1 pro-inflammatory to M2 anti-inflammatory phenotype. In addition, the composite scaffold also exhibits excellent bone-enhancing effects based on the synergistic effect of Mg2+ and Ca2+. In this study, a multifunctional ceramic scaffold (α/ß-TCP@TP-Mg) that integrates anti-inflammatory, antibacterial, and osteoinduction is constructed, which promotes late bone regenerative healing while modulating the early microenvironment of infected bone defects, has a promising application in the treatment of infected bone defects.

Efficacy of chidamide maintenance therapy versus autologous stem cell transplantation versus observation as a post-remission choice in the survival of adult patients with peripheral T-cell lymphoma: Post hoc analysis of a prospective, multicenter, phase 2 study in China.

In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .

Changes in the nutrients, phytochemical profile and antioxidant activity of Rheum officinale Baill. leaf blades during different growth periods.

Rhubarb contains an abundance of compounds and nutrients that promote health through various activities; however, these activities are affected by the harvest season. In this paper, the changes in nutrients, phytochemical profiles and antioxidant activity of Rheum officinale leaf blades (LRO) during different growth periods were investigated. The results showed that LRO is a good source of protein, fiber, and minerals and contains abundant fatty acids; however, as the harvest time increased from March to July, the levels of protein and amino acid decreased, and the levels of other nutrients reached a maximum in May or June. LRO also contains flavonoids, terpenoids, and quinones. As the harvest time increased, the quinone content decreased, possibly due to the unstable chemical properties of quinones at high temperatures. The flavonoid contents reached a maximum in May or June. This study indicated that LRO is a source of nutrients and chemical components and can be used for functional food production. In addition, the nutrients and chemical components related to the antioxidant activity of LRO changed according to the harvest season.

Chelator boosted tumor-retention and pharmacokinetic properties: development of 64Cu labeled radiopharmaceuticals targeting neurotensin receptor.

PURPOSE: Accumulating evidence suggests that neurotensin (NTS) and neurotensin receptors (NTSRs) play key roles in lung cancer progression by triggering multiple oncogenic signaling pathways. This study aims to develop Cu-labeled neurotensin receptor 1 (NTSR1)-targeting agents with the potential for both imaging and therapeutic applications. METHOD: A series of neurotensin receptor antagonists (NRAs) with variable propylamine (PA) linker length and different chelators were synthesized, including [64Cu]Cu-CB-TE2A-iPA-NRA ([64Cu]Cu-4a-c, i = 1, 2, 3), [64Cu]Cu-NOTA-2PA-NRA ([64Cu]Cu-4d), [64Cu]Cu-DOTA-2PA-NRA ([64Cu]Cu-4e, also known as [64Cu]Cu-3BP-227), and [64Cu]Cu-DOTA-VS-2PA-NRA ([64Cu]Cu-4f). The series of small animal PET/CT were conducted in H1299 lung cancer model. The expression profile of NTSR1 was also confirmed by IHC using patient tissue samples. RESULTS: For most of the compounds studied, PET/CT showed prominent tumor uptake and high tumor-to-background contrast, but the tumor retention was strongly influenced by the chelators used. For previously reported 4e, [64Cu]Cu-labeled derivative showed initial high tumor uptake accompanied by rapid tumor washout at 24 h. The newly developed [64Cu]Cu-4d and [64Cu]Cu-4f demonstrated good tumor uptake and tumor-to-background contrast at early time points, but were less promising in tumor retention. In contrast, our lead compound [64Cu]Cu-4b demonstrated 9.57 ± 1.35, 9.44 ± 2.38 and 9.72 ± 4.89%ID/g tumor uptake at 4, 24, and 48 h p.i., respectively. Moderate liver uptake (11.97 ± 3.85, 9.80 ± 3.63, and 7.72 ± 4.68%ID/g at 4, 24, and 48 h p.i.) was observed with low uptake in most other organs. The PA linker was found to have a significant effect on drug distribution. Compared to [64Cu]Cu-4b, [64Cu]Cu-4a had a lower background, including a greatly reduced liver uptake, while the tumor uptake was only moderately reduced. Meanwhile, [64Cu]Cu-4c showed increased uptake in both the tumor and the liver. The clinical relevance of NTSR1 was also demonstrated by the elevated tumor expression in patient tissue samples. CONCLUSIONS: Through the side-by-side comparison, [64Cu]Cu-4b was identified as the lead agent for further evaluation based on its high and sustained tumor uptake and moderate liver uptake. It can not only be used to efficiently detect NTSR1 expression in lung cancer (for diagnosis, patient screening, and treatment monitoring), but also has the great potential to treat NTSR-positive lesions once chelating to the beta emitter 67Cu.

Lifestyle-based subtypes of childhood obesity and their association with cardiometabolic factors: A cluster analysis.

BACKGROUND: Lifestyle factors play an important role in the development and management of childhood obesity and its related cardiometabolic complications. OBJECTIVE/METHODS: We aimed to explore childhood obesity subtypes based on lifestyle factors and examine their association with cardiometabolic health. We included 1550 children with obesity from the National Health and Nutrition Examination Survey. Cluster analysis identified obesity subtypes based on four lifestyle factors (physical activity, diet quality, sedentary time and smoking). Multiple linear regression assessed their association with cardiometabolic factors. RESULTS: Five subtypes of childhood obesity were identified: unhealthy subtype (n = 571; 36.8%), physically active subtype (n = 185; 21.1%), healthy diet subtype (n = 404; 26.1%), smoking subtype (n = 125; 8.1%) and non-sedentary subtype (n = 265; 17.1%). Compared with the unhealthy subtype, the physically active subtype had lower insulin and HOMA-IR levels, and smoking subtype was associated with lower HDL levels. When compared with children with normal weight, all obesity subtypes had worse cardiometabolic profile, except the physically active subtype who had similar DBP, HbA1c and TC levels; smoking subtype who had similar TC levels; and healthy diet and non-sedentary subtypes who had similar DBP levels. CONCLUSION: Children of different lifestyle-based obesity subtypes might have different cardiometabolic risks. Our new classification system might help personalize assessment of childhood obesity.

Yanghanlia caeni gen. nov., sp. nov., a novel taxon within the family Alcaligenaceae isolated from sludge of a pesticide-manufacturing factory.

A Gram-stain-negative bacterium, designated LG-2T, was isolated from sludge collected at a pesticide-manufacturing factory in Jiangsu Province, PR China. Cells of strain LG-2T were strictly aerobic, non-motile and spherical. Growth was observed at 15-42 °C (optimum, 30 °C), pH 6.0-9.0 (optimum, pH 7.0) and 0-3.0 % (w/v) NaCl (optimum, 1.0 %). LG-2T showed 95.5-96.9 % 16S rRNA sequence similarity to type strains in the genera Pusillimonas, Bordetella, Parapusillimonas, Candidimonas and Paracandidimonas of the family Alcaligenaceae. The phylogenomic tree indicated that strain LG-2T was clustered in the family Alcaligenaceae and formed a clade with Paracandidimonas soli IMT-305T, while the phylogenetic trees based on 16S rRNA gene sequences indicated that strain LG-2T formed a distinct clade within the family Alcaligenaceae. The average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity values between LG-2T and its closely related type strains in the genera Pusillimonas, Bordetella, Parapusillimonas, Candidimonas and Paracandidimonas were 70.8-75.3, 18.9-23.7 and 59.6 %-69.3 %, respectively. The major cellular fatty acids were C16 : 0, C17 : 0 cyclo, summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) and summed feature 2 (C12 : 0 aldehyde and/or unknown 10.928). The predominant menaquinone was Q-8. The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, two aminophospholipids, three aminolipids and nine unknown polar lipids. The genome size of strain LG-2T was 3.2 Mb and the DNA G+C content was 63.4 mol%. On the basis of the phenotypic, phylogenetic and genomic results from this study, strain LG-2T represents a novel species of a new genus in the family Alcaligenaceae, for which the name Yanghanlia caeni gen. nov., sp. nov. is proposed, with strain LG-2T (=KCTC 8084T= CCTCC AB 2023123T) as the type strain.

Clinical characteristics and prognosis of patients with newly diagnosed primary central nervous system lymphoma: a multicentre retrospective analysis.

Bruton's tyrosine kinase inhibitors (BTKi) exhibit superior efficacy in relapsed/refractory primary central nervous system lymphoma (PCNSL), but few studies have evaluated patients with newly diagnosed PCNSL, and even fewer studies have evaluated differences in efficacy between treatment with BTKi and traditional chemotherapy. This study retrospectively analyzed the clinical characteristics of 86 patients with PCNSL and identified predictors of poor prognosis for overall survival (OS). After excluding patients who only received palliative care, 82 patients were evaluated for efficacy and survival. According to the induction regimen, patients were divided into the traditional chemotherapy, BTKi combination therapy, and radiotherapy groups; the objective response rates (ORR) of the three groups were 71.4%, 96.2%, and 71.4% (P = 0.037), respectively. Both median progression-free survival and median duration of remission showed statistically significant differences (P = 0.019 and P = 0.030, respectively). The median OS of the BTKi-containing therapy group was also longer than that of the traditional chemotherapy group (not reached versus 47.8 (32.5-63.1) months, P = 0.038).Seventy-one patients who achieved an ORR were further analyzed, and achieved an ORR after four cycles of treatment and maintenance therapy had prolonged OS (P = 0.003 and P = 0.043, respectively). In conclusion, survival, and prognosis of patients with newly diagnosed PCNSL are influenced by the treatment regimen, with the BTKi-containing regimen showing great potential.

The Antioxidant Dendrobium officinale Polysaccharide Modulates Host Metabolism and Gut Microbiota to Alleviate High-Fat Diet-Induced Atherosclerosis in ApoE-/- Mice.

BACKGROUND: The discovery of traditional plants' medicinal and nutritional properties has opened up new avenues for developing pharmaceutical and dietary strategies to prevent atherosclerosis. However, the effect of the antioxidant Dendrobium officinale polysaccharide (DOP) on atherosclerosis is still not elucidated. PURPOSE: This study aims to investigate the inhibitory effect and the potential mechanism of DOP on high-fat diet-induced atherosclerosis in Apolipoprotein E knockout (ApoE-/-) mice. STUDY DESIGN AND METHODS: The identification of DOP was measured by high-performance gel permeation chromatography (HPLC) and Fourier transform infrared spectroscopy (FTIR). We used high-fat diet (HFD)-induced atherosclerosis in ApoE-/- mice as an animal model. In the DOP intervention stage, the DOP group was treated by gavage with 200 µL of 200 mg/kg DOP at regular times each day and continued for eight weeks. We detected changes in serum lipid profiles, inflammatory factors, anti-inflammatory factors, and antioxidant capacity to investigate the effect of the DOP on host metabolism. We also determined microbial composition using 16S rRNA gene sequencing to investigate whether the DOP could improve the structure of the gut microbiota in atherosclerotic mice. RESULTS: DOP effectively inhibited histopathological deterioration in atherosclerotic mice and significantly reduced serum lipid levels, inflammatory factors, and malondialdehyde (F/B) production. Additionally, the levels of anti-inflammatory factors and the activity of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), were significantly increased after DOP intervention. Furthermore, we found that DOP restructures the gut microbiota composition by decreasing the Firmicutes/Bacteroidota (F/B) ratio. The Spearman's correlation analysis indicated that serum lipid profiles, antioxidant activity, and pro-/anti-inflammatory factors were associated with Firmicutes, Bacteroidota, Allobaculum, and Coriobacteriaceae_UCG-002. CONCLUSIONS: This study suggests that DOP has the potential to be developed as a food prebiotic for the treatment of atherosclerosis in the future.

A Reconfigurable DNA Framework Nanotube-Assisted Antiangiogenic Therapy.

A major limitation of tumor antiangiogenic therapy is the pronounced off-target effect, which can lead to unavoidable injury in multiple organs. Ensuring sufficient delivery and controlled release of these antiangiogenic agents at tumor sites is crucial for realizing their clinical application. Here, we develop a smart DNA-based nanodrug, termed Endo-rDFN, by precisely assembling the antiangiogenic agent, endostar (Endo), into a reconfigurable DNA framework nanotube (rDFN) that could recognize tumor-overexpressed nucleolin to achieve the targeted delivery and controllable release of Endo. Endo-rDFN can not only effectively enhance the tumor-targeting capability of Endo and maintain its efficient accumulation in tumor tissues but also achieve on-demand release of Endo at tumor sites via the specific DNA aptamer for tumor-overexpressed nucleolin, named AS1411. We also found that Endo-rDFN exhibited significant inhibition of angiogenesis and tumor growth, while also providing effective protection against multiorgan injury (heart, liver, spleen, kidney, lung, etc.) to some extent, without compromising the function of these organs. Our study demonstrates that rDFN represents a promising vector for reducing antiangiogenic therapy-induced multiorgan injury, highlighting its potential for promoting the clinical application of antiangiogenic agents.

A distributed data processing scheme based on Hadoop for synchrotron radiation experiments.

With the development of synchrotron radiation sources and high-frame-rate detectors, the amount of experimental data collected at synchrotron radiation beamlines has increased exponentially. As a result, data processing for synchrotron radiation experiments has entered the era of big data. It is becoming increasingly important for beamlines to have the capability to process large-scale data in parallel to keep up with the rapid growth of data. Currently, there is no set of data processing solutions based on the big data technology framework for beamlines. Apache Hadoop is a widely used distributed system architecture for solving the problem of massive data storage and computation. This paper presents a set of distributed data processing schemes for beamlines with experimental data using Hadoop. The Hadoop Distributed File System is utilized as the distributed file storage system, and Hadoop YARN serves as the resource scheduler for the distributed computing cluster. A distributed data processing pipeline that can carry out massively parallel computation is designed and developed using Hadoop Spark. The entire data processing platform adopts a distributed microservice architecture, which makes the system easy to expand, reduces module coupling and improves reliability.

Extracellular vesicles derived from immune cells: Role in tumor therapy.

Extracellular vesicles (EVs), which have a lipid nano-sized structure, are known to contain the active components of parental cells and play a crucial role in intercellular communication. The progression and metastasis of tumors are influenced by EVs derived from immune cells, which can simultaneously stimulate and suppress immune responses. In the past few decades, there has been a considerable focus on EVs due to their potential in various areas such as the development of vaccines, delivering drugs, making engineered modifications, and serving as biomarkers for diagnosis and prognosis. This review focuses on the substance information present in EVs derived from innate and adaptive immune cells, their effects on the immune system, and their applications in cancer treatment. While there are still challenges to overcome, it is important to explore the composition of immune cells released vesicles and their potential therapeutic role in tumor therapy. The review also highlights the current limitations and future prospects in utilizing EVs for treatment purposes.

Peiella sedimenti gen. nov., sp. nov., a novel taxon within the family Caulobacteraceae isolated from sediment of a river.

A Gram-stain-negative bacterium, designated XZ-24T, was isolated from sediment of a river in Mianyang city, Sichuan province, PR China. Cells (1.0-2.0 µm long and 0.4-0.5 µm in width) were strictly aerobic, non-spore-forming, rod shaped, prosthecate and motile by means of a polar flagellum. Growth occurred at 10-37 °C (optimum, 30 °C), at pH 5.0-9.0 (optimum pH 7.0) and with 0-3.0 % (w/v) NaCl (optimum 1.0 % NaCl). The results of phylogenetic analysis based on genomes and 16S rRNA gene sequences indicated that XZ-24T formed a distinct phyletic branch within the family Caulobacteraceae and was most closely related to members of the genera Brevundimonas, Caulobacter and Phenylobacterium with 95.3-96.5 % 16S rRNA gene sequence similarities. The average amino acid identities (AAI) between XZ-24T and species of the family Caulobacteraceae were 47.0-64.5 %, which were below the genus boundary (70 %). The predominant cellular fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), C16 : 0, C18 : 1ω7c 11-methyl and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), the isoprenoid quinone was Q-10, and the major polar lipids were 1,2-di-O-acyl-3-O-α-d-glucopyranuronosyl glycerol; 1,2-di-O-acyl-3-O-[d-glucopyranosyl-(1→4)-α-d glucopyranuronosyl] glycerol and phosphatidylglycerol. The genome size of XZ-24T was 2.64 Mb with a DNA G+C content of 68.9 %. On the basis of the evidence presented in this study, strain XZ-24T represents a novel species of a novel genus in the family Caulobacteraceae, for which the name Peiella sedimenti gen. nov., sp. nov. (Type strain XZ-24T=CCTCC AB 20 23 094T=KCTC 8038T) is proposed.

N-glycan biosignatures as a potential diagnostic biomarker for early-stage pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of less than 10%, owing to its late-stage diagnosis. Early detection of pancreatic cancer (PC) can significantly increase survival rates. AIM: To identify the serum biomarker signatures associated with early-stage PDAC by serum N-glycan analysis. METHODS: An extensive patient cohort was used to determine a biomarker signature, including patients with PDAC that was well-defined at an early stage (stages I and II). The biomarker signature was derived from a case-control study using a case-cohort design consisting of 29 patients with stage I, 22 with stage II, 4 with stage III, 16 with stage IV PDAC, and 88 controls. We used multiparametric analysis to identify early-stage PDAC N-glycan signatures and developed an N-glycan signature-based diagnosis model called the "Glyco-model". RESULTS: The biomarker signature was created to discriminate samples derived from patients with PC from those of controls, with a receiver operating characteristic area under the curve of 0.86. In addition, the biomarker signature combined with cancer antigen 19-9 could discriminate patients with PDAC from controls, with a receiver operating characteristic area under the curve of 0.919. Glyco-model demonstrated favorable diagnostic performance in all stages of PC. The diagnostic sensitivity for stage I PDAC was 89.66%. CONCLUSION: In a prospective validation study, this serum biomarker signature may offer a viable method for detecting early-stage PDAC.

Ruixingdingia sedimenti gen. nov., sp. nov., a novel taxon within the family Paracoccaceae isolated from sediment of Qiantang River.

A Gram-stain-negative bacterium, designated LG-4T, was isolated from sediment of Qiantang River in Zhejiang Province, PR China. Cells were strictly aerobic, non-spore-forming, non-motile and short-rod-shaped (1.0-1.2 µm long and 0.7-0.8 µm wide). Growth occurred at 15-42 °C (optimum, 30 °C), at pH 5.0-9.0 (pH 7.0) and at 0-2.0 % (w/v) NaCl (optimum, 0.5 % NaCl). Strain LG-4T showed 95.75-96.90 % 16S rRNA gene sequence similarity to various type strains of the genera Tabrizicola, Pseudotabrizicola, Phaeovulum, Rhodobacter and Wagnerdoeblera of the family Paracoccaceae, and the most closely related strain was Tabrizicola soli ZQBWT (96.90 % similarity). The phylogenomic tree showed that strain LG-4T clustered in the family Paracoccaceae and was positioned outside of the clade composed of the genera Wagnerdoeblera and Falsigemmobacter. The average nucleotide identity and digital DNA-DNA hybridization values between strain LG-4T and the related type strains were in the range of 74.19-77.56 % and 16.70-25.80 %, respectively. The average amino acid identity (AAI) values between strain LG-4T and related type strains of the family Paracoccaceae were 60.94-69.73 %, which are below the genus boundary (70 %). The evolutionary distance (ED) values between LG-4T and the related genera of the family Paracoccaceae were 0.21-0.34, which are within the recommended standard (≥0.21-0.23) for defining a novel genus in the family Paracoccaceae. The predominant cellular fatty acids were C18 : 1 ω7c, C19 : 0 cyclo ω8c, C18 : 0 and C16 : 0, the isoprenoid quinone was Q-10, and the major polar lipids were phospholipid, phosphatidylglycerol, phosphatidylcholine, aminolipid and two unknown polar lipids. The genome size was 4.7 Mb with 68.6 mol% G+C content. On the basis of distinct phylogenetic relationships, low AAI values and high ED values, and differential phenotypic, physiological and biochemical characteristics, strain LG-4T represents a novel species of a new genus in the family Paracoccaceae, for which the name Ruixingdingia sedimenti gen. nov., sp. nov. is proposed. The type strain is LG-4T (=MCCC 1K08849T=KCTC 8136T).

Neurogenesis-Associated Protein, a Potential Prognostic Biomarker in Anti-PD-1 Based Kidney Renal Clear Cell Carcinoma Patient Therapeutics.

The transketolase 1 gene (TKTL1) is an essential factor that contributes to brain development. Some studies have shown the influence of TKTL1 in cancers, but it has been rarely reported in kidney cancer. Furthermore, the role of TKTL1 in the prognosis and tumor infiltration of immune cells in various cancers, particularly kidney cancer, remains unknown. In this study, TKTL1 expression and its clinical characteristics were investigated using a variety of databases. TIMER was used to investigate the relationship between TKTL1 and immune infiltrates in various types of cancer. We also studied the relationship between TKTL1 expression and response to PD-1 blocker immunotherapy in renal cancer. We conducted TKTL1 agonists virtual screening from 13,633 natural compounds (L6020), implemented secondary library construction according to the types of top results, and then conducted secondary virtual screening for 367 alkaloids. Finally, in vitro assays of cell viability assays and colony formation assays were performed to demonstrate the pharmacological potency of the screening of TKTL1 agonists. Using these methods, we determined that TKTL1 significantly affects the prognostic potential in different types of kidney cancer patients. The underlying mechanism might be that the TKTL1 expression level was positively associated with devious immunocytes in kidney renal clear cell carcinoma (KIRC) rather than in kidney renal papillary cell carcinoma (KIRP) and kidney chromophobe (KICH). This recruitment may result from the up-regulation of the mTOR signaling pathway affecting T cell metabolism. We also found that TKTL1 may act as an immunomodulator in KIRC patients' response to anti-PD-1 therapy. Moreover, we also found that piperine and glibenclamide are potent agonists of TKTL1. We have demonstrated, in vitro, that piperine and glibenclamide can inhibit the proliferation and clone formation of Caki-2 cell lines by agonizing the expression of TKTL1. In summary, our discovery implies that TKTL1 may be a promising prognostic biomarker for KIRC patients who respond to anti-PD-1 therapy. Piperine and glibenclamide may be effective therapeutic TKTL1 agonists, providing a theoretical basis for the clinical treatment of kidney cancer.

Efficacy and Toxicity of Moderately Hypofractionated Radiation Therapy with Helical TomoTherapy Versus Conventional Radiation Therapy in Patients with Unresectable Stage III Non-Small Cell Lung Cancer Receiving Concurrent Chemotherapy: A Multicenter, Randomized Phase 3 Trial.

PURPOSE: The standard treatment schedule for unresectable stage III non-small cell lung cancer (NSCLC) is chemotherapy with concurrent radiation therapy (60 Gy delivered in 30 fractions), although moderately hypofractionated radiation therapy (Hypo-RT) has also been considered as an alternative strategy. This study aimed to compare the efficacy and toxicity of moderately Hypo-RT with helical TomoTherapy versus conventionally fractionated radiation therapy (Con-RT) in patients with unresectable stage III NSCLC receiving concurrent chemotherapy. METHODS AND MATERIALS: In this randomized, multicenter, nonblinded phase 3 clinical trial, eligible patients were randomised at a 1:1 ratio to either the Hypo-RT group (60 Gy in 20 fractions) or Con-RT group (60 Gy in 30 fractions). All patients received 2 cycles of concurrent platinum-based chemotherapy plus 2 cycles of consolidation therapy. The primary endpoint was 3-year overall survival (OS) in the intention-to-treat population. The secondary endpoints were progression-free survival and treatment-related adverse events. RESULTS: A total of 146 patients were enrolled from July 27, 2018, to November 1, 2021. The median follow-up was 46 months. The 3-year OS rates in the Hypo-RT and Con-RT groups were 58.4% and 38.4%, respectively (P = .02). The median OS from randomisation was 41 months in the Hypo-RT group and 30 months in the Con-RT group (hazard ratio, 0.61; 95% confidence interval, 0.40-0.94; P = .02). There was no significant difference in the rates of grade ≥2 treatment-related adverse events between the 2 groups. CONCLUSIONS: Moderately Hypo-RT using helical TomoTherapy may improve OS in patients with unresectable stage III NSCLC, while maintaining toxicity rates.