Growth of diamond in liquid metal at 1 atm pressure.

Natural diamonds were (and are) formed (thousands of million years ago) in the upper mantle of Earth in metallic melts at temperatures of 900-1,400 °C and at pressures of 5-6 GPa (refs. 1,2). Diamond is thermodynamically stable under high-pressure and high-temperature conditions as per the phase diagram of carbon3. Scientists at General Electric invented and used a high-pressure and high-temperature apparatus in 1955 to synthesize diamonds by using molten iron sulfide at about 7 GPa and 1,600 °C (refs. 4-6). There is an existing model that diamond can be grown using liquid metals only at both high pressure and high temperature7. Here we describe the growth of diamond crystals and polycrystalline diamond films with no seed particles using liquid metal but at 1 atm pressure and at 1,025 °C, breaking this pattern. Diamond grew in the subsurface of liquid metal composed of gallium, iron, nickel and silicon, by catalytic activation of methane and diffusion of carbon atoms into and within the subsurface regions. We found that the supersaturation of carbon in the liquid metal subsurface leads to the nucleation and growth of diamonds, with Si playing an important part in stabilizing tetravalently bonded carbon clusters that play a part in nucleation. Growth of (metastable) diamond in liquid metal at moderate temperature and 1 atm pressure opens many possibilities for further basic science studies and for the scaling of this type of growth.

Airy-beam holographic sonogenetics for advancing neuromodulation precision and flexibility.

Advancing our understanding of brain function and developing treatments for neurological diseases hinge on the ability to modulate neuronal groups in specific brain areas without invasive techniques. Here, we introduce Airy-beam holographic sonogenetics (AhSonogenetics) as an implant-free, cell type-specific, spatially precise, and flexible neuromodulation approach in freely moving mice. AhSonogenetics utilizes wearable ultrasound devices manufactured using 3D-printed Airy-beam holographic metasurfaces. These devices are designed to manipulate neurons genetically engineered to express ultrasound-sensitive ion channels, enabling precise modulation of specific neuronal populations. By dynamically steering the focus of Airy beams through ultrasound frequency tuning, AhSonogenetics is capable of modulating neuronal populations within specific subregions of the striatum. One notable feature of AhSonogenetics is its ability to flexibly stimulate either the left or right striatum in a single mouse. This flexibility is achieved by simply switching the acoustic metasurface in the wearable ultrasound device, eliminating the need for multiple implants or interventions. AhSonogentocs also integrates seamlessly with in vivo calcium recording via fiber photometry, showcasing its compatibility with optical modalities without cross talk. Moreover, AhSonogenetics can generate double foci for bilateral stimulation and alleviate motor deficits in Parkinson's disease mice. This advancement is significant since many neurological disorders, including Parkinson's disease, involve dysfunction in multiple brain regions. By enabling precise and flexible cell type-specific neuromodulation without invasive procedures, AhSonogenetics provides a powerful tool for investigating intact neural circuits and offers promising interventions for neurological disorders.

TREM2 acts as a receptor for IL-34 to suppress acute myeloid leukemia in mice.

The bone marrow microenvironment supports leukocyte mobilization and differentiation and controls the development of leukemias, including acute myeloid leukemia (AML). Here, we found that the development of AML xenotransplants was suppressed in mice with osteoclasts tuberous sclerosis 1 (Tsc1) deletion. Tsc1-deficient osteoclasts released a high level of interleukin-34 (IL-34), which efficiently induced AML cell differentiation and prevented AML progression in various preclinical models. Conversely, AML development was accelerated in mice deficient in IL-34. Interestingly, IL-34 inhibited AML independent of its known receptors but bound directly to triggering receptor expressed on myeloid cells 2 (TREM2), a key hub of immune signals. TREM2-deficient AML cells and normal myeloid cells were resistant to IL-34 treatment. Mechanistically, IL-34-TREM2 binding rapidly phosphorylated Ras protein activator like 3 and inactivated extracellular signal-regulated protein kinase 1/2 signaling to prevent AML cell proliferation and stimulate differentiation. Furthermore, TREM2 was downregulated in patients with AML and associated with a poor prognosis. This study identified TREM2 as a novel receptor for IL-34, indicating a promising strategy for overcoming AML differentiation blockade in patients with AML.

Molecular classification reveals the sensitivity of lung adenocarcinoma to radiotherapy and immunotherapy: multi-omics clustering based on similarity network fusion.

BACKGROUND: Due to individual differences in tumors and immune systems, the response rate to immunotherapy is low in lung adenocarcinoma (LUAD) patients. Combinations with other therapeutic strategies improve the efficacy of immunotherapy in LUAD patients. Although radioimmunotherapy has been demonstrated to effectively suppress tumors, the underlying mechanisms still need to be investigated. METHODS: Total RNA from LUAD cells was sequenced before and after radiotherapy to identify differentially expressed radiation-associated genes. The similarity network fusion (SNF) algorithm was applied for molecular classification based on radiation-related genes, immune-related genes, methylation data, and somatic mutation data. The changes in gene expression, prognosis, immune cell infiltration, radiosensitivity, chemosensitivity, and sensitivity to immunotherapy were assessed for each subtype. RESULTS: We used the SNF algorithm and multi-omics data to divide TCGA-LUAD patients into three subtypes. Patients with the CS3 subtype had the best prognosis, while those with the CS1 and CS2 subtypes had poorer prognoses. Among the strains tested, CS2 exhibited the most elevated immune cell infiltration and expression of immune checkpoint genes, while CS1 exhibited the least. Patients in the CS2 subgroup were more likely to respond to PD-1 immunotherapy. The CS2 patients were most sensitive to docetaxel and cisplatin, while the CS1 patients were most sensitive to paclitaxel. Experimental validation of signature genes in the CS2 subtype showed that inhibiting the expression of RHCG and TRPA1 could enhance the sensitivity of lung cancer cells to radiation. CONCLUSIONS: In summary, this study identified a risk classifier based on multi-omics data that can guide treatment selection for LUAD patients.

The Arabidopsis stomatal polarity protein BASL mediates distinct processes before and after cell division to coordinate cell size and fate asymmetries.

In many land plants, asymmetric cell divisions (ACDs) create and pattern differentiated cell types on the leaf surface. In the Arabidopsis stomatal lineage, BREAKING OF ASYMMETRY IN THE STOMATAL LINEAGE (BASL) regulates division plane placement and cell fate enforcement. Polarized subcellular localization of BASL is initiated before ACD and persists for many hours after the division in one of the two daughters. Untangling the respective contributions of polarized BASL before and after division is essential to gain a better understanding of its roles in regulating stomatal lineage ACDs. Here, we combine quantitative imaging and lineage tracking with genetic tools that provide temporally restricted BASL expression. We find that pre-division BASL is required for division orientation, whereas BASL polarity post-division ensures proper cell fate commitment. These genetic manipulations allowed us to uncouple daughter-cell size asymmetry from polarity crescent inheritance, revealing independent effects of these two asymmetries on subsequent cell behavior. Finally, we show that there is coordination between the division frequencies of sister cells produced by ACDs, and this coupling requires BASL as an effector of peptide signaling.

A cornucopia of diversity-Ranunculales as a model lineage.

The Ranunculales are a hyperdiverse lineage in many aspects of their phenotype, including growth habit, floral and leaf morphology, reproductive mode, and specialized metabolism. Many Ranunculales species, such as opium poppy and goldenseal, have a high medicinal value. In addition, the order includes a large number of commercially important ornamental plants, such as columbines and larkspurs. The phylogenetic position of the order with respect to monocots and core eudicots and the diversity within this lineage make the Ranunculales an excellent group for studying evolutionary processes by comparative studies. Lately, the phylogeny of Ranunculales was revised, and genetic and genomic resources were developed for many species, allowing comparative analyses at the molecular scale. Here, we review the literature on the resources for genetic manipulation and genome sequencing, the recent phylogeny reconstruction of this order, and its fossil record. Further, we explain their habitat range and delve into the diversity in their floral morphology, focusing on perianth organ identity, floral symmetry, occurrences of spurs and nectaries, sexual and pollination systems, and fruit and dehiscence types. The Ranunculales order offers a wealth of opportunities for scientific exploration across various disciplines and scales, to gain novel insights into plant biology for researchers and plant enthusiasts alike.

URP20 improves corneal injury caused by alkali burns combined with pathogenic bacterial infection in rats.

Corneal alkali burns often occur in industrial production and daily life, combined with infection, and may cause severe eye disease. Oxidative stress and neovascularization (NV) are important factors leading to a poor prognosis. URP20 is an antimicrobial peptide that has been proven to treat bacterial keratitis in rats through antibacterial and anti-NV effects. Therefore, in this study, the protective effect and influence mechanism of URP20 were explored in a rat model of alkali burn together with pathogenic bacteria (Staphylococcus aureus and Escherichia coli) infection. In addition, human umbilical vein endothelial cells (HUVECs) and human corneal epithelial cells (HCECs) were selected to verify the effects of URP20 on vascularization and oxidative stress. The results showed that URP20 treatment could protect corneal tissue, reduce corneal turbidity, and reduce the NV pathological score. Furthermore, URP20 significantly inhibited the expression of the vascularization marker proteins VEGFR2 and CD31. URP20 also reduced the migration ability of HUVECs. In terms of oxidative stress, URP20 significantly upregulated SOD and GSH contents in corneal tissue and HCECs (treated with 200 µM H2O2) and promoted the expression of the antioxidant protein Nrf2/HO-1. At the same time, MDA and ROS levels were also inhibited. In conclusion, URP20 could improve corneal injury combined with bacterial infection in rats caused by alkali burns through antibacterial, anti-NV, and antioxidant activities.

Impact of Isolated Coronary Microvascular Disease Diagnosed Using Various Measurement Modalities on Prognosis: An Updated Systematic Review and Meta-Analysis.

INTRODUCTION: The main aim of this study was to investigate the impact of isolated coronary microvascular disease (CMD) as diagnosed via various modalities on prognosis. METHODS: A systematic literature review of PubMed, Embase, and Cochrane Library databases was conducted to identify relevant studies published up to March 2023. Included studies were required to measure coronary microvascular function and report outcomes in patients without obstructive coronary artery disease (CAD) or any other cardiac pathological characteristics. The primary endpoint was all-cause mortality, and the secondary endpoint was a major adverse cardiac event (MACE). Pooled effects were calculated using random effects models. RESULTS: A total of 27 studies comprising 18,204 subjects were included in the meta-analysis. Indices of coronary microvascular function measurement included coronary angiography-derived index of microcirculatory resistance (caIMR), hyperemic microcirculatory resistance (HMR), coronary flow reserve (CFR), and so on. Patients with isolated CMD exhibited a significantly higher risk of mortality (OR: 2.97, 95% CI, 1.91-4.60, p < 0.0001; HR: 3.38, 95% CI, 1.77-6.47, p = 0.0002) and MACE (OR: 5.82, 95% CI, 3.65-9.29, p < 0.00001; HR: 4.01, 95% CI, 2.59-6.20, p < 0.00001) compared to those without CMD. Subgroup analysis by measurement modality demonstrated consistent and robust pooled effect estimates in various subgroups. CONCLUSION: CMD is significantly associated with an elevated risk of mortality and MACE in patients without obstructive CAD or any other identifiable cardiac pathologies. The utilization of various measurement techniques may have potential advantages in the management of isolated CMD.

Large-scale array for radio astronomy on the farside (LARAF).

At the Royal Society meeting in 2023, we have mainly presented our lunar orbit array concept called DSL, and also briefly introduced a concept of a lunar surface array, LARAF. As the DSL concept had been presented before, in this article, we introduce the LARAF. We propose to build an array in the far side of the Moon, with a master station which handles the data collection and processing, and 20 stations with maximum baseline of 10 km. Each station consists of 12 membrane antenna units, and the stations are connected to the master station by power line and optical fibre. The array will make interferometric observation in the 0.1-50 MHz band during the lunar night, powered by regenerated fuel cells. The whole array can be carried to the lunar surface with a heavy rocket mission, and deployed with a rover in eight months. Such an array would be an important step in the long-term development of lunar-based ultralong wavelength radio astronomy. It has a sufficiently high sensitivity to observe many radio sources in the sky, though still short of the dark age fluctuations. We discuss the possible options in the power supply, data communication, deployment etc. This article is part of a discussion meeting issue 'Astronomy from the Moon: the next decades (part 2)'.

Application of Blood Lymphocyte Immunophenotype and TCR Gene Rearrangement in the Diagnosis of CTCL.

BACKGROUND: The immunophenotype of peripheral blood lymphocytes and T-cell receptor (TCR) gene rearrangement of cutaneous T cell lymphoma (CTCL) patients were retrospectively analyzed to explore their value in the diagnosis of CTCL. METHODS: A total of fifty patients' results were enrolled from 2013 to 2021, including 29 malignant skin disorders and 21 benign skin disorders. The immunophenotype of peripheral blood lymphocytes were analyzed by flow cytometry and TCR gene rearrangement was detected by capillary electrophoresis. Lymphocyte subsets, CD4/CD8 ratio, the percentage of CD3+CD4+CD7- cells and CD45RA/CD45RO ratio was calculated between malignant and benign skin disorders. Peripheral blood lymphocyte immunophenotype and TCR gene rearrangement was compared with skin biopsy to evaluate their sensitivity and specificity. RESULTS: Lymphocyte subsets between malignant and benign groups have no significant difference in percentage of T cell (p > 0.05). The CD4/CD8 ratio is higher in patients with malignant lymphoma than the healthy range. The percentage of CD3+CD4+CD7- cells in malignant groups is higher than that in benign groups and CD45RA/ CD45RO ratio has significant difference between malignant and benign groups (p < 0.05). The sensitivity and specificity of TCR rearrangement for CTCL were 51.7% and 42.9%. The sensitivity and specificity of peripheral blood lymphocyte immunophenotype for CTCL were 44.8% and 33.3%. Combining the two methods, the sensitivity and specificity reached 69.0% and 38.1%, respectively. CONCLUSIONS: CD4/CD8 ratio of lymphocyte subsets, the proportion of CD4+CD7-T cells and CD45RA/CD45RO ratio can effectively distinguish benign and malignant dermatosis. TCR rearrangement method combined with lymphocyte immunophenotype can improve the sensitivity and specificity of CTCL diagnosis.

Age-adjusted Charlson comorbidity index is associated with the risk of osteoporosis in older fall-prone men: a retrospective cohort study.

BACKGROUND: There is growing evidence linking the age-adjusted Charlson comorbidity index (aCCI), an assessment tool for multimorbidity, to fragility fracture and fracture-related postoperative complications. However, the role of multimorbidity in osteoporosis has not yet been thoroughly evaluated. We aimed to investigate the association between aCCI and the risk of osteoporosis in older adults at moderate to high risk of falling. METHODS: A total of 947 men were included from January 2015 to August 2022 in a hospital in Beijing, China. The aCCI was calculated by counting age and each comorbidity according to their weighted scores, and the participants were stratified into two groups by aCCI: low (aCCI < 5), and high (aCCI ≥5). The Kaplan Meier method was used to assess the cumulative incidence of osteoporosis by different levels of aCCI. The Cox proportional hazards regression model was used to estimate the association of aCCI with the risk of osteoporosis. Receiver operating characteristic (ROC) curve was adapted to assess the performance for aCCI in osteoporosis screening. RESULTS: At baseline, the mean age of all patients was 75.7 years, the mean BMI was 24.8 kg/m2, and 531 (56.1%) patients had high aCCI while 416 (43.9%) were having low aCCI. During a median follow-up of 6.6 years, 296 participants developed osteoporosis. Kaplan-Meier survival curves showed that participants with high aCCI had significantly higher cumulative incidence of osteoporosis compared with those had low aCCI (log-rank test: P < 0.001). When aCCI was examined as a continuous variable, the multivariable-adjusted model showed that the osteoporosis risk increased by 12.1% (HR = 1.121, 95% CI 1.041-1.206, P = 0.002) as aCCI increased by one unit. When aCCI was changed to a categorical variable, the multivariable-adjusted hazard ratios associated with different levels of aCCI [low (reference group) and high] were 1.00 and 1.557 (95% CI 1.223-1.983) for osteoporosis (P <  0.001), respectively. The aCCI (cutoff ≥5) revealed an area under ROC curve (AUC) of 0.566 (95%CI 0.527-0.605, P = 0.001) in identifying osteoporosis in older fall-prone men, with sensitivity of 64.9% and specificity of 47.9%. CONCLUSIONS: The current study indicated an association of higher aCCI with an increased risk of osteoporosis among older fall-prone men, supporting the possibility of aCCI as a marker of long-term skeletal-related adverse clinical outcomes.

Benefit finding in chronic kidney disease patients receiving hemodialysis: a cross-sectional study.

BACKGROUND AND OBJECTIVES: The psychological problems of hemodialysis (HD) patients are prominent, and benefit finding (BF) have been proven beneficial to physical and mental health, fewer researchers explored BF in HD patients. The aim of this study was to investigate the current status of BF in patients with chronic kidney disease and to analyze the factors influencing it in order to provide a reference for subsequent interventions. METHODS: A cross-sectional study was done on 246 HD patients by convenience sampling in the hemodialysis center of a 3 A hospital in Shanghai from March to September 2019. The measures include General Information Questionnaire, Benefit Finding Scale, Perceived Social Support Scale, General Self-efficacy Scale, and Simplified Coping Style scale. RESULTS: The median (interquartile range, IQR) score of BF was 66 (IQR = 19) and it was lower compared with other chronic diseases. Significant differences in BF scores were found between different age groups, HD duration categories, and understanding degrees of HD. Taking BF as the dependent variable, the results of multiple linear regression analysis showed that age, duration of HD, family support, other support, positive coping, and self-efficacy entered the regression equation to explain 43.8% of the total variation. Social support played an indirect effect in the relationship between positive coping and BF, accounting for 54.1% of the total effect. CONCLUSION: The BF of HD patients is worrisome and affected by many factors. Medical staff could pay attention to the positive psychology of HD patients, and construct individualized interventions according to the influencing factors to improve their BF level and achieve physical and mental health.

Knowledge, attitude, and practice toward weight management among diabetic patients in Qidong City, Jiangsu Province.

BACKGROUND: Weight management is an effective prevention and treatment strategy for diabetes mellitus. This study aimed to assess the knowledge, attitude, and practice (KAP) of diabetic patients towards weight management. METHODS: Diabetic patients treated at Qidong City, Jiangsu Province, between January 2023 and June 2023 were included in this cross-sectional study. A self-designed questionnaire was used to collect their demographic characteristics and KAP toward weight management. Structural equation modeling (SEM) was employed to examine the inter-relationships among KAP scores. RESULTS: Among a total of 503 valid questionnaires that were collected, 55.07% were filled out by men and 54.67% by those aged < 60 years. The mean scores for knowledge, attitude, and practice were 8.03 ± 3.525 (possible range: 0-13), 31.88 ± 3.524 (possible range: 10-50), and 22.24 ± 3.318 (possible range: 9-45), respectively. Pearson's correlation analysis revealed the knowledge was positively associated with attitude (r = 0.295, P < 0.001) and practice (r = 0.131, P < 0.001), and attitude was positively associated with practice (r = 0.140, P = 0.002). SEM demonstrated positive associations between knowledge and attitude (ß = 0.28, P < 0.001), and attitude and practice (ß = 0.09, P = 0.019). Moreover, older age was negatively associated with knowledge (ß=-0.04, P = 0.001), while higher education (ß = 1.220, P < 0.001), increased monthly income (ß = 0.779, P < 0.001), diagnosis of fatty liver (ß = 1.03, P = 0.002), and screening for excess visceral fat (ß = 1.11, P = 0.002) were positively associated with knowledge. CONCLUSION: Diabetic patients showed moderate knowledge, neutral attitudes, and inappropriate practices toward weight management. Knowledge was positively associated with attitude and practice. These findings provided valuable directions for healthcare interventions targeting improved KAP status of weight management among diabetic patients.

Association of serum metal levels with type 2 diabetes: A prospective cohort and mediating effects of metabolites analysis in Chinese population.

Several studies have suggested an association between exposure to various metals and the onset of type 2 diabetes (T2D). However, the results vary across different studies. We aimed to investigate the associations between serum metal concentrations and the risk of developing T2D among 8734 participants using a prospective cohort study design. We utilized inductively coupled plasmamass spectrometry (ICP-MS) to assess the serum concentrations of 27 metals. Cox regression was applied to calculate the hazard ratios (HRs) for the associations between serum metal concentrations on the risk of developing T2D. Additionally, 196 incident T2D cases and 208 healthy control participants were randomly selected for serum metabolite measurement using an untargeted metabolomics approach to evaluate the mediating role of serum metabolite in the relationship between serum metal concentrations and the risk of developing T2D with a nested casecontrol study design. In the cohort study, after Bonferroni correction, the serum concentrations of zinc (Zn), mercury (Hg), and thallium (Tl) were positively associated with the risk of developing T2D, whereas the serum concentrations of manganese (Mn), molybdenum (Mo), barium (Ba), lutetium (Lu), and lead (Pb) were negatively associated with the risk of developing T2D. After adding these eight metals, the predictive ability increased significantly compared with that of the traditional clinical model (AUC: 0.791 vs. 0.772, P=8.85×10-5). In the nested casecontrol study, a machine learning analysis revealed that the serum concentrations of 14 out of 1579 detected metabolites were associated with the risk of developing T2D. According to generalized linear regression models, 7 of these metabolites were significantly associated with the serum concentrations of the identified metals. The mediation analysis showed that two metabolites (2-methyl-1,2-dihydrophthalazin-1-one and mestranol) mediated 46.81% and 58.70%, respectively, of the association between the serum Pb concentration and the risk of developing T2D. Our study suggested that serum Mn, Zn, Mo, Ba, Lu, Hg, Tl, and Pb were associated with T2D risk. Two metabolites mediated the associations between the serum Pb concentration and the risk of developing T2D.

3-(Methylthio)Propionic Acid from Bacillus thuringiensis Berliner Exhibits High Nematicidal Activity against the Root Knot Nematode Meloidogyne incognita (Kofoid and White) Chitwood.

Root knot nematodes cause serious damage to global agricultural production annually. Given that traditional chemical fumigant nematicides are harmful to non-target organisms and the environment, the development of biocontrol strategies has attracted significant attention in recent years. In this study, it was found that the Bacillus thuringiensis Berliner strain NBIN-863 exhibits strong fumigant nematicidal activity and has a high attraction effect on Meloidogyne incognita (Kofoid and White) Chitwood. Four volatile organic compounds (VOCs) produced by NBIN-863 were identified using solid-phase microextraction and gas chromatography-mass spectrometry. The nematicidal activity of four VOCs, namely, N-methylformamide, propenamide, 3-(methylthio)propionic acid, and phenylmalonic acid, was detected. Among these compounds, 3-(methylthio)propionic acid exhibited the highest direct contact nematicidal activity against M. incognita, with an LC50 value of 6.27 µg/mL at 24 h. In the fumigant bioassay, the mortality rate of M. incognita treated with 1 mg/mL of 3-(methylthio)propionic acid for 24 h increased to 69.93%. Furthermore, 3-(methylthio)propionic acid also exhibited an inhibitory effect on the egg-hatching of M. incognita. Using chemotaxis assays, it was determined that 3-(methylthio)propionic acid was highly attractive to M. incognita. In pot experiments, the application of 3-(methylthio)propionic acid resulted in a reduction in gall numbers, decreasing the number of galls per gram of tomato root from 97.58 to 6.97. Additionally, the root length and plant height of the treated plants showed significant increases in comparison with the control group. The current study suggests that 3-(methylthio)propionic acid is a novel nematicidal virulence factor of B. thuringiensis. Our research provides evidence for the potential use of NBIN-863 or its VOCs in biocontrol against root knot nematodes.

Genomic and Comparative Transcriptomic Analyses Reveal Key Genes Associated with the Biosynthesis Regulation of Okaramine B in Penicillium daleae NBP-49626.

Restricted production of fungal secondary metabolites hinders the ability to conduct comprehensive research and development of novel biopesticides. Okaramine B from Penicillium demonstrates remarkable insecticidal efficacy; however, its biosynthetic yield is low, and its regulatory mechanism remains unknown. The present study found that the yield difference was influenced by fermentation modes in okaramine-producing strains and performed genomic and comparative transcriptome analysis of P. daleae strain NBP-49626, which exhibits significant features. The NBP-49626 genome is 37.4 Mb, and it encodes 10,131 protein-encoding genes. Up to 5097 differentially expressed genes (DEGs) were identified during the submerged and semi-solid fermentation processes. The oka gene cluster, lacking regulatory and transport genes, displayed distinct transcriptional patterns in response to the fermentation modes and yield of Okaramine B. Although transcription trends of most known global regulatory genes are inconsistent with those of oka, this study identified five potential regulatory genes, including two novel Zn(II)2Cys6 transcription factors, Reg2 and Reg19. A significant correlation was also observed between tryptophan metabolism and Okaramine B yields. In addition, several transporter genes were identified as DEGs. These results were confirmed using real-time quantitative PCR. This study provides comprehensive information regarding the regulatory mechanism of Okaramine B biosynthesis in Penicillium and is critical to the further yield improvement for the development of insecticides.

A Fusion of Taq DNA Polymerase with the CL7 Protein from Escherichia coli Remarkably Improves DNA Amplification.

DNA polymerases are important enzymes that synthesize DNA molecules and therefore are critical to various scientific fields as essential components of in vitro DNA synthesis reactions, including PCR. Modern diagnostics, molecular biology, and genetic engineering require DNA polymerases with improved performance. This study aimed to obtain and characterize a new CL7-Taq fusion DNA polymerase, in which the DNA coding sequence of Taq DNA polymerase was fused with that of CL7, a variant of CE7 (Colicin E7 DNase) from Escherichia coli. The resulting novel recombinant open reading frame was cloned and expressed in E. coli. The recombinant CL7-Taq protein exhibited excellent thermostability, extension rate, sensitivity, and resistance to PCR inhibitors. Our results showed that the sensitivity of CL7-Taq DNA polymerase was 100-fold higher than that of wild-type Taq, which required a template concentration of at least 1.8 × 105 nM. Moreover, the extension rate of CL7-Taq was 4 kb/min, which remarkably exceeded the rate of Taq DNA polymerase (2 kb/min). Furthermore, the CL7 fusion protein showed increased resistance to inhibitors of DNA amplification, including lactoferrin, heparin, and blood. Single-cope human genomic targets were readily available from whole blood, and pretreatment to purify the template DNA was not required. Thus, this is a novel enzyme that improved the properties of Taq DNA polymerase, and thus may have wide application in molecular biology and diagnostics.

The association between outdoor light at night exposure and adult obesity in Northeastern China.

Previous studies have linked exposure to light at night (LAN) with various health outcomes, but evidence is limited for the LAN-obesity association. Thestudy analysed data from 24,845 participants of the 33 Communities Chinese Health Study and obesity (BMI ≥28 kg/m2) was defined according to the Working Group on Obesity in China. The Global Radiance Calibrated Nighttime Lights data were used to estimate participants' LAN exposure. The mixed-effect regression models examined the LAN-BMI and LAN-obesity association. We found that higher LAN exposure was significantly associated with greater BMI and higher risk of obesity. Changes of BMI and the odds ratios (ORs) of obesity and 95% confidence intervals (CIs) for 2nd, 3rd, and 4th against the 1st quartile of LAN exposure were 0.363 (0.208, 0.519), 0.364 (0.211, 0.516) and 0.217 (0.051, 0.383); 1.228 (1.099, 1.371), 1.356 (1.196, 1.538) and 1.269 (1.124, 1.433), respectively. Age and regular exercise showed significant modification effects on the LAN-obesity association.

Haglund resection versus Haglund non-resection for calcific insertional Achilles tendinopathy with Haglund deformity: A retrospective study.

BACKGROUND: Calcific insertional Achilles tendinopathy(CIAT) with Haglund deformity is a type of recalcitrant tendinopathy. The necessity of concomitant removal of Haglund deformity during CIAT treatment is controversial. The present study aimed to evaluate the functional outcomes between Haglund resection and Haglund non-resection in the treatment of CIAT with Haglund deformity. METHODS: A retrospective study included 29 patients who were underwent Achilles tendon debridement, bursal excision, and subsequent tendon reattachment.for CIAT with Haglund deformity. All patients were divided into 2 groups according to Haglund resection (resection group, n = 16) and Haglund non-resection (non-resection group, n = 13) using the parallel line method on lateral calcaneal X ray after surgery. Patients were evaluated in terms of the American Orthopedic Foot and Ankle Society (AOFAS), Visual Analog Scale (VAS) and Victorian Institute of Sports Assessment-Achilles (VISA-A) scores and the mean time of activities of daily living (ADL). Anatomy changes included the Fowler-Philip angle, calcaneal pitch angle and Achilles tendon force arm were measured with radiography preoperatively and postoperatively. RESULTS: Both groups exhibited a significant increase in AOFAS, VAS and VISA-A scores after surgery. There were no significant differences between the resection group and the non-resection group for the AOFAS (92.38 ± 5.7 vs. 93.15 ± 12.17; P = 0.82), VAS (0.5 ± 0.52 vs. 0.61 ± 0.87; P = 0.66) and VISA-A questionnaire (82.56 ± 13.46 vs. 74.92 ± 16.4; P = 0.18) at the latest follow-up. The mean time of ADL in the non-resection group was significantly faster compared to that of the resection group (8.15 ± 2.51 weeks vs. 11.31 ± 4.06 weeks, P = 0.02). The Fowler-Philip angle of the resection group decreased from 55.55° ± 12.34° preoperatively to 44.52° ± 10.24° at the latest follow-up (P = 0.001). The Fowler-Philip angle of the non-resection group decreased from 54.38° ± 8.41° preoperatively to 46.52° ± 8.02° at the latest follow-up (P = 0.016). The calcaneal pitch angle of the resection group increased from 22.76° ± 5.37° preoperatively to 25.98° ± 6. 4° at the latest follow-up (P = 0.018). The Achilles tendon force arm of the resection group decreased from 178.50 mm ± 5.37 mm preoperatively to 173.90 mm ± 8.07 mm at the latest follow-up (P = 0.018). CONCLUSION: Resection or non-resection of the posterosuperior calcaneal tuberosity for CIAT with Haglund deformity would both provide satisfactory functional outcomes. Haglund non-resection may expedite patients' return to their daily activities, suggesting a Haglund deformity resection may be unnecessary in the surgical treatment for CIAT with Haglund deformity.

Ataxia telangiectasia mutated kinase inhibition promotes irradiation-induced PD-L1 expression in tumour-associated macrophages through IFN-I/JAK signalling pathway.

Tumour-associated macrophages (TAMs) are one of the primary sources of PD-L1 expression in the tumour microenvironment (TME). Ionizing radiation (IR) promotes PD-L1 expression in tumour cells. However, the effect of IR on macrophage PD-L1 expression and the underlying mechanisms remain unclear. ATM kinase, as the key kinase for initiating DNA damage repair (DDR) process, is associated with innate immune STING axis activation. Here, we explored the molecular mechanism implicated in macrophage PD-L1 expression regulated by IR as well as the role of ATM kinase in this process. IR-regulated PD-L1 expression in macrophages and associated signalling pathways were explored by in vitro studies using murine and human macrophage cell lines. A colorectal xenograft murine model was employed to demonstrate the impact of targeting ATM and PD-L1 expression in TAMs following IR on growth of tumour in vivo. IR up-regulated PD-L1 expression in macrophages, which was further augmented by ATM kinase inhibition. ATM inhibition increased IR-induced DNA damage, which activated STING/interferon regulatory factor 3 (IRF3) signalling pathway and up-regulated type I interferon (IFN-I) expression in macrophages. IFN-I bound to the IFN α receptor 1 on macrophages, activated the downstream JAK1 and STAT1/3 signalling and eventually led to PD-L1 up-expression. ATM inhibition augmented IR-induced PD-L1 expression in macrophages and CD8+ T cell infiltration, and promoted anti-tumour efficacy in vivo. These results suggested that ATM inhibition promoted IR-induced PD-L1 expression through the activation of innate immunity in TAMs, which provided a novel approach to enhance the anti-tumour efficacy of RT.