CDC73 serves as a tumour-promoting factor in oesophageal cancer.

The role of human cell division cycle 73 (CDC73) in human cancers has sparked controversy; however, its significance in oesophageal cancer remains elusive. This study aimed to elucidate CDC73 expression and its biological implications in human oesophageal cancer. Our findings unveiled a notable upregulation of CDC73 in both oesophageal cancer cell lines and tissues. Importantly, elevated CDC73 levels in patients with oesophageal cancer correlated with an unfavourable prognosis. Functional investigations revealed that CDC73 knockdown effectively curtailed the proliferation and growth of oesophageal cancer cells both in vitro and in vivo. Mechanistically, RRP15 emerged as a potential downstream target of CDC73 through a screening process involving identification of the top co-expressed genes, subsequent knockdown experiments, and observation of significant inhibition of cell proliferation, with RRP15 showing the most pronounced effect. This finding was further supported by the positive correlation observed between CDC73 and RRP15 in ESCA samples analysed using the ENCORI Pan-Cancer Analysis Platform. Notably, depletion of RRP15 in CDC73-overexpressing cells led to a shift from augmented to diminished tumour growth. Collectively, our findings underscore the pivotal role of CDC73 in oesophageal cancer through the modulation of RRP15 expression, suggesting CDC73 as a potential therapeutic target for treating oesophageal cancer.

Triggered Release of Ampicillin from Metallic Implant Coatings for Combating Periprosthetic Infections.

Periprosthetic infections caused by Staphylococcus aureus (S. aureus) pose unique challenges in orthopedic surgeries, in part due to the bacterium's capacity to invade surrounding bone tissues besides forming recalcitrant biofilms on implant surfaces. We previously developed prophylactic implant coatings for the on-demand release of vancomycin, triggered by the cleavage of an oligonucleotide (Oligo) linker by micrococcal nuclease (MN) secreted by the Gram-positive bacterium, to eradicate S. aureus surrounding the implant in vitro and in vivo. Building upon this coating platform, here we explore the feasibility of extending the on-demand release to ampicillin, a broad-spectrum aminopenicillin ß-lactam antibiotic that is more effective than vancomycin in killing Gram-negative bacteria that may accompany S. aureus infections. The amino group of ampicillin was successfully conjugated to the carboxyl end of an MN-sensitive Oligo covalently integrated in a polymethacrylate hydrogel coating applied to titanium alloy pins. The resultant Oligo-Ampicillin hydrogel coating released the ß-lactam in the presence of S. aureus and successfully cleared nearby S. aureus in vitro. When the Oligo-Ampicillin-coated pin was delivered to a rat femoral canal inoculated with 1000 cfu S. aureus, it prevented periprosthetic infection with timely on-demand drug release. The clearance of the bacteria from the pin surface as well as surrounding tissue persisted over 3 months, with no local or systemic toxicity observed with the coating. The negatively charged Oligo fragment attached to ampicillin upon cleavage from the coating did diminish the antibiotic's potency against S. aureus and Escherichia coli (E. coli) to varying degrees, likely due to electrostatic repulsion by the anionic surfaces of the bacteria. Although the on-demand release of the ß-lactam led to adequate killing of S. aureus but not E. coli in the presence of a mixture of the bacteria, strong inhibition of the colonization of the remaining E. coli on hydrogel coating was observed. These findings will inspire considerations of alternative broad-spectrum antibiotics, optimized drug conjugation, and Oligo linker engineering for more effective protection against polymicrobial periprosthetic infections.

Ecofriendly Controlled-Release Insecticide Carrier: pH-/Temperature-Responsive Rosin-Derived Hydrogels for Avermectin Delivery against Mythimna separata (Walker).

The exploration of environmentally friendly, less toxic, sustained-release insecticide is increasing with the growing demand for food to meet the requirements of the expanding population. As a sustained-release carrier, the unique, environmentally friendly intelligent responsive hydrogel system is an important factor in improving the efficiency of insecticide utilization and accurate release. In this study, we developed a facile approach for incorporating the natural compound rosin (dehydroabietic acid, DA) and zinc ions (Zn2+) into a poly(N-isopropylacrylamide) (PNIPAM) hydrogel network to construct a controlled-release hydrogel carrier (DA-PNIPAM-Zn2+). Then, the model insecticide avermectin (AVM) was encapsulated in the carrier at a drug loading rate of 36.32% to form AVM@DA-PNIPAM-Zn2+. Surprisingly, the smart controlled carrier exhibited environmental responsiveness, strongly enhanced mechanical properties, self-healing ability, hydrophobicity, and photostability to ensure a balance between environmental friendliness and the precision of the drug release. The release experiments showed that the carboxyl and amide groups in the polymer chains alter the intermolecular forces within the hydrogel meshes and ingredient diffusion by changing temperatures (25 and 40 °C) and pH values (5.8, 7.4, and 8.5), leading to different release behaviors. The insecticidal activity of the AVM@DA-PNIPAM-Zn2+ against oriental armyworms was good, with an effective minimum toxicity toward aquatic animals. Therefore, AVM@DA-PNIPAM-Zn2+ is an effective drug delivery system against oriental armyworms. We anticipate that this ecofriendly, sustainable, smart-response carrier may broaden the utilization rosin and its possible applications in the agricultural sector.

Predictive DNA damage signaling for low­dose ionizing radiation.

Numerous studies have attempted to develop biological markers for the response to radiation for broad and straightforward application in the field of radiation. Based on a public database, the present study selected several molecules involved in the DNA damage repair response, cell cycle regulation and cytokine signaling as promising candidates for low­dose radiation­sensitive markers. The HuT 78 and IM­9 cell lines were irradiated in a concentration­dependent manner, and the expression of these molecules was analyzed using western blot analysis. Notably, the activation of ataxia telangiectasia mutated (ATM), checkpoint kinase 2 (CHK2), p53 and H2A histone family member X (H2AX) significantly increased in a concentration­dependent manner, which was also observed in human peripheral blood mononuclear cells. To determine the radioprotective effects of cinobufagin, as an ATM and CHK2 activator, an in vivo model was employed using sub­lethal and lethal doses in irradiated mice. Treatment with cinobufagin increased the number of bone marrow cells in sub­lethal irradiated mice, and slightly elongated the survival of lethally irradiated mice, although the difference was not statistically significant. Therefore, KU60019, BML­277, pifithrin­α, and nutlin­3a were evaluated for their ability to modulate radiation­induced cell death. The use of BML­277 led to a decrease in radiation­induced p­CHK2 and γH2AX levels and mitigated radiation­induced apoptosis. On the whole, the present study provides a novel approach for developing drug candidates based on the profiling of biological radiation­sensitive markers. These markers hold promise for predicting radiation exposure and assessing the associated human risk.

Biomechanical Effect of Different Posterior Fixation Techniques on Stability and Adjacent Segment Degeneration in Treating Thoracolumbar Burst Fracture With Osteoporosis: A Finite Element Analysis.

STUDY DESIGN: Finite element analysis. OBJECTIVE: To investigate the biomechanical effect of four posterior fixation tcehniques on stability and adjacent segment degeneration in treating thoracolumbar burst fractures with osteoporosis. SUMMARY OF BACKGROUND DATA: In terms of stability and adjacent segment degeneration, there remains no consensus or guidelines on the optimal technique for the treatment of thoracolumbar burst fractures in patients with osteoporosis. METHODS: Images of CT scans were imported into MIMICS and further processed by Geomagic to build 3-dimensional models of the T10-L5 region. A v-shaped osteotomy was performed on the L1 vertebral body to simulate a burst fracture in the setting of osteoporosis. Subsequently, four fixation techniques were designed using SolidWorks software. Range of motion (ROM) of the global spine, ROM distribution, ROM of adjacent segment, Von Mises stress on adjacent intervertebral discs and facet joints were analyzed. RESULTS: Among the four groups, the cortical bone screw fixation (CBT) showed the highest global ROM at 1.86°, while long-segmented pedicle screw fixation (LSPS) had the lowest global ROM at 1.25°. The LSPS had the smallest percentage of ROM of fractured vertebral body to fixed segment at 75.04%, suggesting the highest stability after fixation. The maximum ROM of the adjacent segment was observed in the CBT at 1.32°, while the LSPS exhibited the smallest at 0.89°. However, the LSPS group experienced larger maximum stress on the adjacent intervertebral discs (9.60MPa) and facet joints (3.36MPa), indicating an increasing risk of adjacent segment disease. CONCLUSION: LSPS provided the greatest stability, while CBT provided the smallest amount of stability. However, the elevated stress on adjacent intervertebral discs and facet joints after LSPS fixation increased the possibility of adjacent segment degeneration. Cement-augmented pedicle screw fixation (CAS) and combined cortical bone screw and pedicle screw fixation (CBT-PS) demonstrated significant biomechanical advantages in providing moderate fixation strength while reducing stress on the intervertebral discs and facet joints.

The mechanisms of ferroptosis in the pathogenesis of kidney diseases.

The pathological features of acute and chronic kidney diseases are closely associated with cell death in glomeruli and tubules. Ferroptosis is a form of programmed cell death characterized by iron overload-induced oxidative stress. Ferroptosis has recently gained increasing attention as a pathogenic mechanism of kidney damage. Specifically, the ferroptosis signaling pathway has been found to be involved in the pathological process of acute and chronic kidney injury, potentially contributing to the development of both acute and chronic kidney diseases. This paper aims to elucidate the underlying mechanisms of ferroptosis and its role in the pathogenesis of kidney disease, highlighting its significance and proposing novel directions for its treatment.

NLRP3-dependent pyroptosis exacerbates coxsackievirus A16 and coxsackievirus A10-induced inflammatory response and viral replication in SH-SY5Y cells.

Coxsackievirus A16 (CV-A16) and coxsackievirus A10 (CV-A10), more commonly etiological agents of hand, foot and mouth disease (HFMD), are capable of causing severe neurological syndromes with high fatalities, but their neuropathogenesis has rarely been studied. Mounting evidence indicated that pyroptosis is an inflammatory form of cell death that might be widely involved in the pathogenic mechanisms of neurotropic viruses. Our study was designed to examine the effects of NLRP3-mediated pyroptosis in CV-A16- and CV-A10-induced inflammatory neuropathologic formation. In this work, it was showed that SH-SY5Y cells were susceptible to CV-A16 and CV-A10, and meanwhile their infections could result in a decreasing cell viability and an increasing LDH release as well as Caspase1 activation. Moreover, CV-A16 and CV-A10 infections triggered NLRP3-mediated pyroptosis and promoted the release of inflammatory cytokines. Additionally, activated NLRP3 accelerated the pyroptosis formation and aggravated the inflammatory response, but inhibited NLRP3 had a dampening effect on the above situation. Finally, it was further revealed that NLRP3 agonist enhanced the viral replication, but NLRP3 inhibitor suppressed the viral replication, suggesting that NLRP3-driven pyroptosis might support CV-A16 and CV-A10 production in SH-SY5Y cells. Together, our findings demonstrated a mechanism by which CV-A16 and CV-A10 induce inflammatory responses by evoking NLRP3 inflammasome-regulated pyroptosis, which in turn further stimulated the viral replication, providing novel insights into the pathogenesis of CV-A16 and CV-A10 infections.

Inflammatory bowel disease alters in vivo distribution of orally administrated nanoparticles: Revealing via SERS tag labeling technique.

Nanoparticles (NPs) could be uptake orally and exposed to digestive tract through various sources such as particulate pollutant, nanomedicine and food additive. Inflammatory bowel disease (IBD), as a global disease, induced disruption of the intestinal mucosal barrier and thus altered in vivo distribution of NPs as a possible consequence. However, related information was relatively scarce. Herein, in vivo distribution of typical silica (SiO2) and titania (TiO2) NPs was investigated in healthy and IBD models at cell and animal levels via a surface-enhanced Raman scattering (SERS) tag labeling technique. The labeled NPs were composed of gold SERS tag core and SiO2 (or TiO2) shell, demonstrating sensitive and characteristic SERS signals ideal to trace the NPs in vivo. Cell SERS mapping revealed that protein corona from IBD intestinal fluid decreased uptake of NPs by lipopolysaccharide-induced RAW264.7 cells compared with normal intestinal fluid protein corona. SERS signal detection combined with inductively coupled plasma mass spectrometry (ICP-MS) analysis of mouse tissues (heart, liver, spleen, lung and kidney) indicated that both NPs tended to accumulate in lung specifically after oral administration for IBD mouse (6 out of 20 mice for SiO2 and 4 out of 16 mice for TiO2 were detected in lung). Comparatively, no NP signals were detected in all tissues from healthy mice. These findings suggested that there might be a greater risk associated with the oral uptake of NPs in IBD patients due to altered in vivo distribution of NPs.

Exploring the prognostic significance of iron death­related lncRNAs in colorectal cancer: A systematic review and meta­analysis.

Colorectal cancer is a significant health challenge globally, with its prognosis associated with the profile of molecular biomarkers. Recently, the role of iron death-associated long non-coding (lnc)RNAs in cancer development has garnered attention; however, their expression patterns and prognostic value in colorectal cancer remain poorly elucidated. The present study aimed to assess the expression levels of iron death-related lncRNAs in colorectal cancer tissues and evaluate their relationship with patient outcomes through a comprehensive meta-analysis. Systematic searches were performed across multiple databases, including PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang and VIP databases, to identify studies relevant to the objective of the present study. Selected studies met predetermined inclusion criteria, from which data were extracted. R software version 4.3.1 was used for the meta-analysis, evaluating the association between iron death-related lncRNAs expression and colorectal cancer prognosis. Publication bias was assessed using funnel plot analysis, and Begg's and Egger's test. A total of 11 studies, including 3,984 patients with colorectal cancer, were included in the present meta-analysis. The results demonstrated a significant association between iron death-related lncRNAs and tumor stage classification [odds ratio (OR)=2.00; 95% confidence interval (CI), 1.77-2.24]. Notably, a significant association was also revealed between iron death-related lncRNAs and T stage classification in colorectal cancer (OR=1.82; 95% CI, 1.50-2.20). Furthermore, a statistically significant association was demonstrated between iron death-related lncRNAs and lymph node metastasis in colorectal cancer (OR=1.31; 95% CI, 1.03-1.66). The findings also highlighted a significant association between iron death-associated lncRNA and distant metastasis in colon cancer (OR=2.04; 95% CI, 1.62-2.56). Moreover, a significant association between iron death-related lncRNAs and risk score in colorectal cancer was revealed (OR=1.75; 95% CI, 1.25-2.46). In conclusion, the findings of the present meta-analysis underscore the potential of high ferroptosis-associated lncRNA expression as an indicator of adverse outcomes in colorectal cancer, suggesting their viability as biomarkers for cancer progression and prognosis. This insight opens potential new avenues for clinical application and further research into colorectal cancer management.

Interaction Pattern Disentangling for Multi-Agent Reinforcement Learning.

Deep cooperative multi-agent reinforcement learning has demonstrated its remarkable success over a wide spectrum of complex control tasks. However, recent advances in multi-agent learning mainly focus on value decomposition while leaving entity interactions still intertwined, which easily leads to over-fitting on noisy interactions between entities. In this work, we introduce a novel interactiOn Pattern disenTangling (OPT) method, to disentangle the entity interactions into interaction prototypes, each of which represents an underlying interaction pattern within a subgroup of the entities. OPT facilitates filtering the noisy interactions between irrelevant entities and thus significantly improves generalizability as well as interpretability. Specifically, OPT introduces a sparse disagreement mechanism to encourage sparsity and diversity among discovered interaction prototypes. Then the model selectively restructures these prototypes into a compact interaction pattern by an aggregator with learnable weights. To alleviate the training instability issue caused by partial observability, we propose to maximize the mutual information between the aggregation weights and the history behaviors of each agent. Experiments on single-task, multi-task and zero-shot benchmarks demonstrate that the proposed method yields results superior to the state-of-the-art counterparts. Our code is available at https://github.com/liushunyu/OPT.

Chitosan-based GOx@Co-MOF composite hydrogel: A promising strategy for enhanced antibacterial and wound healing effects.

A novel composite hydrogel was synthesized via Schiff base reaction between chitosan and di-functional poly(ethylene glycol) (DF-PEG), incorporating glucose oxidase (GOx) and cobalt metal-organic frameworks (Co-MOF). The resulting CS/PEG/GOx@Co-MOF composite hydrogel was characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), and energy-dispersive X-ray spectroscopy (EDS). The results confirmed successful integration and uniform distribution of Co-MOF within the hydrogel matrix. Functionally, the hydrogel exploits the catalytic decomposition of glucose by GOx to generate gluconic acid and hydrogen peroxide (H2O2), while Co-MOF gradually releases metal ions and protects GOx. This synergy enhanced the antibacterial activity of the composite hydrogel against both Gram-positive (S. aureus) and Gram-negative bacteria (E. coli), outperforming conventional chitosan-based hydrogels. The potential of the composite hydrogel in treating wound infections was evaluated through antibacterial and wound healing experiments. Overall, CS/PEG/GOx@Co-MOF hydrogel holds great promise for the treatment of wound infections, paving the way for further research and potential clinical applications.

Research on High-Stability Composite Control Methods for Telescope Pointing Systems under Multiple Disturbances.

During the operation of space gravitational wave detectors, the constellation configuration formed by three satellites gradually deviates from the ideal 60° angle due to the periodic variations in orbits. To ensure the stability of inter-satellite laser links, active compensation of the breathing angle variation within the constellation plane is achieved by rotating the optical subassembly through the telescope pointing mechanism. This paper proposes a high-performance robust composite control method designed to enhance the robust stability, disturbance rejection, and tracking performance of the telescope pointing system. Specifically, based on the dynamic model of the telescope pointing mechanism and the disturbance noise model, an H∞ controller has been designed to ensure system stability and disturbance rejection capabilities. Meanwhile, employing the method of an H∞ norm optimized disturbance observer (HODOB) enhances the nonlinear friction rejection ability of the telescope pointing system. The simulation results indicate that, compared to the traditional disturbance observer (DOB) design, utilizing the HODOB method can enhance the tracking accuracy and pointing stability of the telescope pointing system by an order of magnitude. Furthermore, the proposed composite control method improves the overall system performance, ensuring that the stability of the telescope pointing system meets the 10 nrad/Hz1/2 @0.1 mHz~1 Hz requirement specified for the TianQin mission.

Fast and effective molecular property prediction with transferability map.

Effective transfer learning for molecular property prediction has shown considerable strength in addressing insufficient labeled molecules. Many existing methods either disregard the quantitative relationship between source and target properties, risking negative transfer, or require intensive training on target tasks. To quantify transferability concerning task-relatedness, we propose Principal Gradient-based Measurement (PGM) for transferring molecular property prediction ability. First, we design an optimization-free scheme to calculate a principal gradient for approximating the direction of model optimization on a molecular property prediction dataset. We have analyzed the close connection between the principal gradient and model optimization through mathematical proof. PGM measures the transferability as the distance between the principal gradient obtained from the source dataset and that derived from the target dataset. Then, we perform PGM on various molecular property prediction datasets to build a quantitative transferability map for source dataset selection. Finally, we evaluate PGM on multiple combinations of transfer learning tasks across 12 benchmark molecular property prediction datasets and demonstrate that it can serve as fast and effective guidance to improve the performance of a target task. This work contributes to more efficient discovery of drugs, materials, and catalysts by offering a task-relatedness quantification prior to transfer learning and understanding the relationship between chemical properties.

Transport of polyethylene and polypropylene microplastics under the action of agricultural chemicals: Role of pesticide adjuvants and neonicotinoid active ingredients.

Understanding the impact of various agricultural chemical components on the fate and transport of microplastics (MPs) in the subsurface is essential. In this study, column experiments on saturated porous media were conducted to explore the influence of the coexistence environment of pesticide adjuvants (surfactants) and active ingredients (neonicotinoids) on the transport of polyethylene (PE) and polypropylene (PP) MPs. An anionic surfactant (sodium dodecyl sulfate (SDS)), a nonionic surfactant (nonylphenol ethoxylate (NP-40)), and three neonicotinoid insecticides (acetamiprid, dinotefuran, and nitenpyram) could independently increase MP migration by 9.31%-61.01% by improving the hydrophilicity. Acetamiprid or dinotefuran reduced the adhesion work of the binary system by competing with SDS for adsorption sites, thereby inhibiting PE mobility. However, nitenpyram in the mixture was not easily adsorbed on the surface of PE MPs together with SDS because of nitenpyram's high hydrophilicity. Neonicotinoid molecules could not reduce the hydrophilic modification of SDS on PP MPs by competing for adsorption sites. Owing to their weak charge and adhesion work of nonionic surfactants (-4.80 mV and 28.45 kT for PE and -8.21 mV and 17.64 kT for PP), neonicotinoids tended to occupy the adsorption sites originally belonging to NP-40. The long molecular chain of NP-40 made it difficult for high-concentration neonicotinoids to affect the adhesion on MPs. In addition, NP-40 was harder to peel off from the MP surface than SDS, leading to a larger MP transport ability in the sand column.

Red Fluorescent Molecule with Aggregation-Induced Emission Based on Dehydroabietic Acid Diarylamine for Bioimaging.

In this paper, molecules with AIE red light properties were designed by coupling dehydroabietic acid diarylamine and 2,3-diphenylfumaronitrile, which were designated 2DTPA-CN and 2TPA-CN. The emission wavelengths were 683 nm and 701 nm, respectively. The 2DTPA-CN and 2TPA-CN showed typical AIE characteristics with large Stokes shifts of 7.4 × 104 cm-1 and 6.7 × 104 cm-1, respectively. The obvious solvatochromism and electron cloud distributions of HOMO/LUMO in the ground and excited states both reveal the intramolecular charge transfer (ICT) effect. The 2DTPA-CN, boasting exceptional biocompatibility, was successfully prepared into nanoparticles (NPs), which were applied to tumor cell imaging, showing good bioimaging effects both in vitro imaging in live cells and in vivo imaging in live mice. The results demonstrated that it possesses significant potential as an effective bioimaging reagent for the detection of tumor cells. Furthermore, the incorporation of 2,3-diphenylfumaronitrile moieties to dehydroabietic acid diarylamine emerged as a proficient approach to broaden the emission wavelengths of rosin-based fluorescent materials.

African swine fever virus infection regulates pyroptosis by cleaving gasdermin A (GSDMA) via active caspase-3 and caspase-4.

African swine fever (ASF), caused by the African swine fever virus (ASFV), is a viral hemorrhagic disease that affects domestic pigs and wild boars. ASFV infection causes extensive tissue damage, and the associated mechanism is poorly understood. Pyroptosis is characterized by the activation of inflammatory caspases and pore formation in the cellular plasma membrane, resulting in the release of inflammatory cytokines and cell damage. How ASFV infection regulates pyroptosis remains unclear. Here, using small interfering RNA assay and overexpression methods, we report that ASFV infection regulated pyroptosis by cleaving the pyroptosis execution protein gasdermin A (GSDMA). ASFV infection activated caspase-3 and caspase-4, which specifically cleaved GSDMA at D75-P76 and D241-V242 to produce GSDMA into five fragments, including GSDMA-N1-75, GSDMA-N1-241, and GSDMA-N76-241 fragments at the N terminal end of GSDMA. Only GSDMA-N1-241, which was produced in the late stage of ASFV infection, triggered pyroptosis and inhibited ASFV replication. The fragments GSDMA-N1-75 and GSDMA-N76-241 lose the ability to induce pyroptosis. Overall ASFV infection differentially regulates pyroptosis by GSDMA in the indicated phase, which may be conducive to its own replication. Our findings reveal a novel molecular mechanism for the regulation of pyroptosis.

The erosive effect of pomegranate juice on enamel: An in vitro study.

AIM: Dental erosion is a chemical-mechanical process that leads to the loss of dental hard tissues. This study aimed to investigate the effect of pomegranate juice on the enamel. METHODS: Enamel blocks were randomly divided into three groups: deionized water, cola, and pomegranate juice. The blocks were immersed in the solutions four times a day for 14 days, and stored in artificial saliva for the remaining period. The surface hardness was measured on days 7 and 14. The surface structures of the demineralized blocks were observed via scanning electron microscopy (SEM), and the depth of demineralization was observed via confocal laser scanning microscopy (CLSM). The pH, calcium, and phosphorus levels of the three solutions were analyzed. RESULTS: The microhardness values of the blocks in the pomegranate juice and cola groups decreased with the increase in the demineralization time. The blocks in the pomegranate juice group exhibited large fractures in the enamel column, whereas those in the cola group had pitted enamels with destruction of the interstitial enamel column. Compared with cola group, fluorescent penetration increased in pomegranate juice (P < 0.01). The pH of cola (2.32 ± 0.09) was lower than that of pomegranate juice (3.16 ± 0.16). Furthermore, the calcium content in pomegranate juice was significantly higher than that in cola (P < 0.01). Alternatively, the concentration of phosphorous in cola was significantly higher than that in pomegranate juice (P < 0.01). CONCLUSION: These findings indicate that pomegranate juice can cause enamel demineralization with an erosive potential comparable to that of cola.

Self-regulated efficient production of L-threonine via an artificial quorum sensing system in engineered Escherichia coli.

Imbalance in carbon flux distribution is one of the most important factors affecting the further increase in the yield of high value-added natural products in microbial metabolic engineering. Meanwhile, the most common inducible expression systems are difficult to achieve industrial-scale production due to the addition of high-cost or toxic inducers during the fermentation process. Quorum sensing system, as a typical model for density-dependent induction of gene expression, has been widely applied in synthetic biology. However, there are currently few reports for efficient production of microbial natural products by using quorum sensing system to self-regulate carbon flux distribution. Here, we designed an artificial quorum sensing system to achieve efficient production of L-threonine in engineered Escherichia coli by altering the carbon flux distribution of the central metabolic pathways at specific periods. Under the combination of switch module and production module, the system was applied to divide the microbial fermentation process into two stages including growth and production, and improve the production of L-threonine by self-inducing the expression of pyruvate carboxylase and threonine extracellular transporter protease after a sufficient amount of cell growth. The final strain TWF106/pST1011, pST1042pr could produce 118.2 g/L L-threonine with a yield of 0.57 g/g glucose and a productivity of 2.46 g/(L· h). The establishment of this system has important guidance and application value for the production of other high value-added chemicals in microorganisms by self-regulation.

Coexistence of pulmonary arterial hypertension and straight back syndrome in a patient with a novel BMPR2 variant affecting cytoplasmic tail domain.

BACKGROUND: Pathologic variants in the bone morphogenetic protein receptor-2 (BMPR2) gene cause a pulmonary arterial hypertension phenotype in an autosomal-dominant pattern with incomplete penetrance. Straight back syndrome is one of the causes of pseudo-heart diseases. To date, no cases of idiopathic or heritable pulmonary arterial hypertension with straight back syndrome have been reported. CASE PRESENTATION: A 30-year-old female was diagnosed with pulmonary arterial hypertension by right heart catheterization. Computed tomography revealed a decreased anteroposterior thoracic space with heart compression, indicating a straight back syndrome. Genetic analysis by whole exome sequencing identified a novel c.2423_2424delGT (p.G808Gfs*4) germline frameshift variant within BMPR2 affecting the cytoplasmic tail domain. CONCLUSIONS: This is the first report of different straight back characteristics in heritable pulmonary arterial hypertension with a novel germline BMPR2 variant. This finding may provide a new perspective on the variable penetrance of the pulmonary arterial hypertension phenotype.