Ectoine hyperproduction by engineered Halomonas bluephagenesis.

Ectoine, a crucial osmoprotectant for salt adaptation in halophiles, has gained growing interest in cosmetics and medical industries. However, its production remains challenged by stringent fermentation process in model microorganisms and low production level in its native producers. Here, we systematically engineered the native ectoine producer Halomonas bluephagenesis for ectoine production by overexpressing ectABC operon, increasing precursors availability, enhancing product transport system and optimizing its growth medium. The final engineered H. bluephagenesis produced 85 g/L ectoine in 52 h under open unsterile incubation in a 7 L bioreactor in the absence of plasmid, antibiotic or inducer. Furthermore, it was successfully demonstrated the feasibility of decoupling salt concentration with ectoine synthesis and co-production with bioplastic P(3HB-co-4HB) by the engineered H. bluephagenesis. The unsterile fermentation process and significantly increased ectoine titer indicate that H. bluephagenesis as the chassis of Next-Generation Industrial Biotechnology (NGIB), is promising for the biomanufacturing of not only intracellular bioplastic PHA but also small molecular compound such as ectoine.

Chrysomycins, Anti-Tuberculosis C-Glycoside Polyketides from Streptomyces sp. MS751.

A new dimeric C-glycoside polyketide chrysomycin F (1), along with four new monomeric compounds, chrysomycins G (2), H (3), I (4), J (5), as well as three known analogues, chrysomycins A (6), B (7), and C (8), were isolated and characterised from a strain of Streptomyces sp. obtained from a sediment sample collected from the South China Sea. Their structures were determined by detailed spectroscopic analysis. Chrysomycin F contains two diastereomers, whose structures were further elucidated by a biomimetic [2 + 2] photodimerisation of chrysomycin A. Chrysomycins B and C showed potent anti-tuberculosis activity against both wild-type Mycobacterium tuberculosis and a number of clinically isolated MDR M. tuberculosis strains.

Bone mesenchymal stem cell-derived extracellular vesicles containing NORAD promote osteosarcoma by miR-30c-5p.

Osteosarcoma is a bone tumor that often affects children, adolescents and young people. Non-coding RNA activated by DNA damage (NORAD) can promote the proliferation of cancer cells in multiple tumors. Thus, the current study set out to explore the role of NORAD derived from extracellular vesicles (EVs) of bone mesenchymal stem cells (BMSCs) in osteosarcoma. First, NORAD was highly expressed in osteosarcoma cells and tissues, which might be associated with the progression and metastasis of osteosarcoma. We isolated EVs from the characterized BMSCs, and found that NORAD was transferred from BMSCs to osteosarcoma cells via EVs in the co-culture system. Consequently, NORAD delivered by BMSC-derived EVs promoted the proliferation and invasion of osteosarcoma cells. Subsequently, bioinformatics analyses suggested potential binding relationship between NORAD and microRNA-30c-5p (miR-30c-5p) as well as between miR-30c-5p and Krueppel-like factor 10 (KLF10), and the results of which were further verified by dual luciferase reporter gene assay, RNA immunoprecipitation, and RNA pull-down assay. Mechanistically, NORAD acted as a sponge of miR-30c-5p and up-regulated the expression of KLF10 where miR-30-c-5p mimic declined the effect induced by NORAD on cancer cells. The osteosarcoma cells were injected into mice to develop tumor growth and metastasis models. In these two models, injection of BMSC-EVs elevated NORAD expression and KLF10 but reduced miR-30c-5p expression, whereby suppressing tumor growth and lung metastasis. To conclude, BMSC-EVs deliver NORAD to osteosarcoma cells to regulate the miR-30c-5p/KLF10 axis, thereby accelerating the progression and metastasis of osteosarcoma.

Improved volume variable cluster model method for crystal-lattice optimization: effect on isotope fractionation factor.

The isotopic fractionation factor and element partition coefficient can be calculated only after the geometric optimization of the molecular clusters is completed. Optimization directly affects the accuracy of some parameters, such as the average bond length, molecular volume, harmonic vibrational frequency, and other thermodynamic parameters. Here, we used the improved volume variable cluster model (VVCM) method to optimize the molecular clusters of a typical oxide, quartz. We documented the average bond length and relative volume change. Finally, we extracted the harmonic vibrational frequencies and calculated the equilibrium fractionation factor of the silicon and oxygen isotopes. Given its performance in geometrical optimization and isotope fractionation factor calculation, we further applied the improved VVCM method to calculate isotope equilibrium fractionation factors of Cd and Zn between the hydroxide (Zn-Al layered double hydroxide), carbonate (cadmium-containing calcite) and their aqueous solutions under superficial conditions. We summarized a detailed procedure and used it to re-evaluate published theoretical results for cadmium-containing hydroxyapatite, emphasizing the relative volume change for all clusters and confirming the optimal point charge arrangement (PCA). The results showed that the average bond length and isotope fractionation factor are consistent with those published in previous studies, and the relative volume changes are considerably lower than the results calculated using the periodic boundary method. Specifically, the average Si-O bond length of quartz was 1.63 Å, and the relative volume change of quartz centered on silicon atoms was  - 0.39%. The average Zn-O bond length in the Zn-Al-layered double hydroxide was 2.10 Å, with a relative volume change of 1.96%. Cadmium-containing calcite had an average Cd-O bond length of 2.28 Å, with a relative volume change of 0.45%. At 298 K, the equilibrium fractionation factors between quartz, Zn-Al-layered double hydroxide, cadmium-containing calcite, and their corresponding aqueous solutions were [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] respectively. These results strongly support the reliability of the improved VVCM method for geometric optimization of molecular clusters.

Moiré Superlattice-Induced Superconductivity in One-Unit-Cell FeTe.

In this work, we demonstrate that the nonsuperconducting single-layer FeTe can become superconducting when its structure is properly tuned by epitaxially growing it on Bi2Te3 thin films. The properties of the single-layer FeTe deviate strongly from its bulk counterpart, as evidenced by the emergence of a large superconductivity gap (3.3 meV) and an apparent 8 × 2 superlattice (SL). Our first-principles calculations indicate that the 8 × 2 SL and the emergence of the novel superconducting phase are essentially the result of the structural change in FeTe due to the presence of the underlying Bi2Te3 layer. The structural change in FeTe likely suppresses the antiferromagnetic order in the FeTe and leads to superconductivity. Our work clearly demonstrates that moiré pattern engineering in a heterostructure is a reachable dimension for investigating novel materials and material properties.

Superconductivity in Single-Quintuple-Layer Bi2Te3 Grown on Epitaxial FeTe.

How an interfacial superconductivity emerges during the nucleation and epitaxy is of great importance not only for unveiling the physical insights but also for finding a feasible way to tune the superconductivity via interfacial engineering. In this work, we report the nanoscale creation of a robust and relatively homogeneous interfacial superconductivity (TC ≈ 13 K) on the epitaxial FeTe surface, by van der Waals epitaxy of single-quintuple-layer topological insulator Bi2Te3. Our study suggests that the superconductivity in the Bi2Te3/FeTe heterostructure is generated at the interface and that the superconductivity at the interface does not enhance or weaken with the increase of the Bi2Te3 thickness beyond 1 quintuple layer (QL). The observation of the topological surface states crossing Fermi energy in the Bi2Te3/FeTe heterostructure with the average Bi2Te3 thickness of about 20 QL provides further evidence that this heterostructure may potentially host Majorana zero modes.

Evidence for Magnetic Skyrmions at the Interface of Ferromagnet/Topological-Insulator Heterostructures.

The heterostructures of the ferromagnet (Cr2Te3) and topological insulator (Bi2Te3) have been grown by molecular beam epitaxy. The topological Hall effect as evidence of the existence of magnetic skyrmions has been observed in the samples in which Cr2Te3 was grown on top of Bi2Te3. Detailed structural characterizations have unambiguously revealed the presence of intercalated Bi bilayer nanosheets right at the interface of those samples. The atomistic spin-dynamics simulations have further confirmed the existence of magnetic skyrmions in such systems. The heterostructures of ferromagnet and topological insulator that host magnetic skyrmions may provide an important building block for next generation of spintronics devices.

New Diketopiperazines from a Marine-Derived Fungus Strain Aspergillus versicolor MF180151.

Six new diketopiperazines, (±)-7,8-epoxy-brevianamide Q ((±)-1), (±)-8-hydroxy-brevianamide R ((±)-2), and (±)-8-epihydroxy-brevianamide R ((±)-3), together with four known compounds, (±)-brevianamide R ((±)-4), versicolorin B (5) and averufin (6), were isolated from a marine-derived fungus strain Aspergillus versicolor MF180151, which was recovered from a sediment sample collected from the Bohai Sea, China. The chemical structures were established by 1D- and 2D-NMR spectra and HR-ESI-MS. 1 is the first sample of brevianamides with an epoxy moiety. Their bioactivities were evaluated against Candida albicans, Bacillus subtilis, Staphylococcus aureus, methicillin-resistant S. aureus, Pseudomonas aeruginosa, and Bacillus Calmette-Guérin. Compounds 1-4 showed no activities against the pathogens, and compounds 5 and 6 showed moderate activities against S. aureus and methicillin-resistant S. aureus.

Madurastatin B3, a rare aziridine derivative from actinomycete Nocardiopsis sp. LS150010 with potent anti-tuberculosis activity.

Since the discovery of the first antibiotic, natural products have played an important role in chemistry, biology and medicine. To explore the potential of bioactive compounds from microbes isolated from the southeast of Tibet, China, a crude extract library was constructed and screened against Staphylococcus aureus. The strain Nocardiopsis sp. LS150010 was scaled up and subjected to further chemical studies, resulting in the identification of N-salicyloyl-2-aminopropan-1,3-diol (2) and its rare aziridine derivative, madurastatin B3 (1). Their structures were determined by detailed analysis of 1D, 2D NMR and HRMS data. Compounds 1 and 2 displayed significant inhibitory activity against S. aureus and methicillin resistant S. aureus, with MIC values of 6.25 µg/mL. Compound 1 also showed potent inhibitory activity against Bacillus subtilis and Escherichia coli, as well as activity in a Mycobacterium tuberculosis Bacillus Calmette-Guérin infected THP-1 cell model.

USA's expanded overseas tuberculosis screening program: a retrospective study in China.

BACKGROUND: To address increasing tuberculosis (TB) incidence in foreign-born populations, immigrant TB screening programs have been implemented in the USA. These programs are modified periodically, the effectiveness of which have been disputed. The aim of this retrospective study was to assess the value of the 2009 Technical Instructions for Tuberculosis Screening and Treatment Using Cultures and Directly Observed Therapy (CDOT TB TI) in a cohort of the USA permanent-resident applicants from China. METHODS: Standardized forms were used to collect demographic, clinical, and laboratory data of Chinese individuals screened at the Guangdong International Travel Healthcare Center for permanent residence in the USA between October 08, 2009 and December 31, 2012. Applicants' data were further retrospectively evaluated by three experienced panel physicians and radiologists according to the 1991 Technical Instructions for Tuberculosis Screening and Treatment (TI). TB cases and characteristics identified by the 1991 and expanded 2009 programs were compared. RESULTS: The CDOT TB TI identified more than twice as many TB cases that required treatment completion before clearance for travel than the 1991 TI (270 vs. 131). In addition, the expanded screening program identified more cases of negative sputum smear but positive culture (181 vs. 44), and more cases of radiography suggestive of inactive (22 vs. 3) and active (248 vs. 128) TB. Specifically, the 1991 TI screening program failed to identify 25/38 (65.79%) cases carrying drug-resistant isolates, and 13/131 (9.92%) would have been inappropriately treated. Moreover, 220/270 (81.48%) of the cases were asymptomatic, which were identified by screening and subsequently treated. Improved chest radiograph and sputum negative conversion occurred in all treated cases. CONCLUSION: CDOT TB TI, a screening program that includes sputum culture and drug susceptibility tests, identifies a greater number of TB cases, likely contributing to the overall decrease in TB prevalence in host (USA) and origin (China) countries.

Three new sterigmatocystin analogues from marine-derived fungus Aspergillus versicolor MF359.

During the systematic screening of active compounds from marine-derived fungi, the extract of a strain of Aspergillus versicolor MF359 isolated from a marine sponge of Hymeniacidon perleve was identified for detailed chemical investigation. Three new secondary metabolites, named hemiacetal sterigmatocystin (1), acyl-hemiacetal sterigmatocystin (2), and 5-methoxydihydrosterigmatocystin (3), together with a known compound, aversin (4), were characterized. 1 represents a first structure of sterigmatocystin hemiacetal from nature. The antibacterial activities of these identified compounds were evaluated against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Bacillus subtilis, and Pseudomonas aeruginosa. Compound 3 showed activity against S. aureus and B. subtilis with MIC values of 12.5 and 3.125 µg/mL, respectively.

8-Hydroxy-2'-deoxyguanosine expression predicts outcome of esophageal cancer.

Esophageal cancer is characterized by increased oxidative stress and the production of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is one of the main mutagenic modifications of DNA. We analyzed the predictive value of 8-OHdG expression on postoperative survival of patients with esophageal cancer with univariate and multivariate analysis. The high levels of 8-OHdG are associated with significantly shorter survival time by log-rank test using Kaplan-Meier methods. Moreover, the level of 8-OHdG expression was identified as an independent predictor for esophageal cancer outcome using Cox proportional hazards model analysis (relative risk, 0.294; 95% confidence interval, 0.178-0.487; P = .000). These results suggest that oxidative damage marker of 8-OHdG is a useful prognostic marker in esophageal cancer. The analysis of 8-OHdG levels can help in the identification of patient subgroups that are at high risk for poor disease outcomes.

PHA is not just a bioplastic!

Polyhydroxyalkanoates (PHA) have evolved into versatile biopolymers, transcending their origins as mere bioplastics. This extensive review delves into the multifaceted landscape of PHA applications, shedding light on the diverse industries that have harnessed their potential. PHA has proven to be an invaluable eco-conscious option for packaging materials, finding use in films foams, paper coatings and even straws. In the textile industry, PHA offers a sustainable alternative, while its application as a carbon source for denitrification in wastewater treatment showcases its versatility in environmental remediation. In addition, PHA has made notable contributions to the medical and consumer sectors, with various roles ranging from 3D printing, tissue engineering implants, and cell growth matrices to drug delivery carriers, and cosmetic products. Through metabolic engineering efforts, PHA can be fine-tuned to align with the specific requirements of each industry, enabling the customization of material properties such as ductility, elasticity, thermal conductivity, and transparency. To unleash PHA's full potential, bridging the gap between research and commercial viability is paramount. Successful PHA production scale-up hinges on establishing direct supply chains to specific application domains, including packaging, food and beverage materials, medical devices, and agriculture. This review underscores that PHA's future rests on ongoing exploration across these industries and more, paving the way for PHA to supplant conventional plastics and foster a circular economy.

Asymmetric edge supercurrents in MoTe2 Josephson junctions.

To investigate the higher order topology in MoTe2, the supercurrent interference phenomena in Nb/MoTe2/Nb planar Josephson junctions have been systematically studied. By analyzing the obtained interference pattern of the critical supercurrents and performing a comparative study of the edge-touched and untouched junctions, it's found that the supercurrent is dominated by the edges, rather than the bulk or surfaces of MoTe2. An asymmetric Josephson effect with a field-tunable sign is also observed, indicating the nontrivial origin of the edge states. These results not only provide initial evidence for the hinge states in the higher order topological insulator MoTe2, but also demonstrate the potential applications of MoTe2-based Josephson junctions in rectifying the supercurrent.

Retraction: Strontium-doped gelatin scaffolds promote M2 macrophage switch and angiogenesis through modulating the polarization of neutrophils.

Retraction of 'Strontium-doped gelatin scaffolds promote M2 macrophage switch and angiogenesis through modulating the polarization of neutrophils' by Tao Li et al., Biomater. Sci., 2021, 9, 2931-2946, https://doi.org/10.1039/D0BM02126A.

HOXB9 promotes osteosarcoma cell survival and malignancy under glucose starvation via upregulating SPP1 expression.

Homeobox B9 (HOXB9) has been shown to play a critical role in several tumors. However, the precise biological mechanisms and functions of HOXB9 in osteosarcoma remain largely unknown. In this study, we found that HOXB9 was increased upon glucose starvation. Elevated HOXB9 suppressed osteosarcoma cell death and supported cell growth and migration under glucose starvation. Further mechanistic studies demonstrated that HOXB9 directly bound to the promoter of secreted phosphoprotein 1 (SPP1) and transcriptionally upregulated SPP1 expression which then led cell death decrease and cell growth increase under glucose deprivation environment. Clinically, HOXB9 was significantly upregulated in osteosarcoma compared with normal tissues and increase of HOXB9 expression was positively associated with the elevation of SPP1 in osteosarcoma. Overall, our study illustrates that HOXB9 contributes to malignancy in osteosarcoma and inhibits cell death through transcriptional upregulating SPP1 under glucose starvation.

Establishing and Validating an Aging-Related Prognostic Signature in Osteosarcoma.

Aging is an inevitable process that biological changes accumulate with time and results in increased susceptibility to different tumors. But currently, aging-related genes (ARGs) in osteosarcoma were not clear. We investigated the potential prognostic role of ARGs and established an ARG-based prognostic signature for osteosarcoma. The transcriptome data and corresponding clinicopathological information of patients with osteosarcoma were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Molecular subtypes were generated based on prognosis-related ARGs obtained from univariate Cox analysis. With ARGs, a risk signature was built by univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Differences in clinicopathological features, immune infiltration, immune checkpoints, responsiveness to immunotherapy and chemotherapy, and biological pathways were assessed according to molecular subtypes and the risk signature. Based on risk signature and clinicopathological variables, a nomogram was established and validated. Three molecular subtypes with distinct clinical outcomes were classified based on 36 prognostic ARGs for osteosarcoma. A nine-ARG-based signature in the TCGA cohort, including BMP8A, CORT, SLC17A9, VEGFA, GAL, SSX1, RASGRP2, SDC3, and EVI2B, has been created and developed and could well perform patient stratification into the high- and low-risk groups. There were significant differences in clinicopathological features, immune checkpoints and infiltration, responsiveness to immunotherapy and chemotherapy, cancer stem cell, and biological pathways among the molecular subtypes. The risk signature and metastatic status were identified as independent prognostic factors for osteosarcoma. A nomogram combining ARG-based risk signature and metastatic status was established, showing great prediction accuracy and clinical benefit for osteosarcoma OS. We characterized three ARG-based molecular subtypes with distinct characteristics and built an ARG-based risk signature for osteosarcoma prognosis, which could facilitate prognosis prediction and making personalized treatment in osteosarcoma.

Predictive value of gut microbiota in long-term blood pressure control: a cross-sectional study.

OBJECTIVES: To investigate the prediction of long-term blood pressure control using the intestinal flora of patients with hypertension. METHODS: A total of 125 patients with primary grade-2 hypertension who attended the cardiovascular department of Hebei Province Hospital of Chinese Medicine between April 2021 and April 2022 were enrolled; these included 65 patients with substandard long-term blood pressure control (the uncontrolled group) and 60 patients with standard long-term blood pressure control (the controlled group). General clinical data and data on morning stools and diet were recorded for all the enrolled patients. The 16 s rDNA sequencing of faecal intestinal flora was also performed to analyse the differences in intestinal flora between the two groups of patients and to investigate the relationship between blood pressure compliance and the presence of flora. RESULTS: The intestinal flora of the two groups of patients differed in terms of the Firmicutes-Bacteroidetes ratio (F/B), α-diversity analysis (Chao1, ACE and Shannon) results and ß-diversity analysis results. At the genus level, the number of Streptococcus and Paraprevotella in patients in the uncontrolled group was greater than that of the controlled group, and the level of Akkermansia and Bifidobacterium was lower than that in the controlled group. A logistic regression analysis of the difference factors found differences in ACE, F/B, Streptococcus, Paraprevotella and Akkermansia in the two groups; these differences remained after correcting for age, gender and body mass index. The receiver operating characteristic curves revealed the following: ACE (area under the curve [AUC] = 85.282), Streptococcus (AUC = 82.705), Akkermansia (AUC = 77.333), Paraprevotella (AUC = 66.154) and F/B (AUC = 60.436). CONCLUSIONS: There were significant differences in the intestinal flora of the patients in the controlled blood group compared with that of the uncontrolled group. Therefore, the ACE, genus levels of Streptococcus and Akkermansia could provide some prediction of late blood pressure compliance or non-compliance in patients with hypertension.

[The degradation of plastics and the production of polyhydroxyalkanoates (PHA)].

In recent years, the petroleum-based plastic pollution problem has been causing global attention. The idea of "degradation and up-cycling of plastics" was proposed for solving the environmental pollution caused by non-degradable plastics. Following this idea, plastics would be firstly degraded and then reconstructed. Polyhydroxyalkanoates (PHA) can be produced from the degraded plastic monomers as a choice to recycle among various plastics. PHA, a family of biopolyesters synthesized by many microbes, have attracted great interest in industrial, agricultural and medical sectors due to its biodegradability, biocompatibility, thermoplasticity and carbon neutrality. Moreover, the regulations on PHA monomer compositions, processing technology, and modification methods may further improve the material properties, making PHA a promising alternative to traditional plastics. Furthermore, the application of the "next-generation industrial biotechnology (NGIB)" utilizing extremophiles for PHA production is expected to enhance the PHA market competitiveness, promoting this environmentally friendly bio-based material to partially replace petroleum-based products, and achieve sustainable development with carbon-neutrality. This review summarizes the basic material properties, plastic upcycling via PHA biosynthesis, processing and modification methods of PHA, and biosynthesis of novel PHA.