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Implant-related osteomyelitis is a formidable hurdle in the clinical setting and is characterized by inflammation, infection, and consequential bone destruction. Therefore, effective reactive oxygen species (ROS) scavenging, bacterial killing, and subsequent bone tissue repair are urgently needed for the treatment of difficult-to-heal osteomyelitis. Herein, we utilized the eddy-thermal effect of magnesium (Mg) implants under an alternating magnetic field (AMF) for the controlled release of H2 gas and ions (OH− and Mg2+) for the treatment of osteomyelitis. H2 released by Mg rods under AMFs effectively scavenged cytotoxic ROS, exhibiting anti-inflammatory effects and consequently disrupting the environment of bacterial infections. In addition, the OH− hindered the energy metabolism of bacteria by effectively neutralizing protons within the microenvironment. Moreover, H2 impaired the permeability of bacterial membranes and expedited the damage induced by OH−. This synergistic AMF-induced H2 and proton depletion treatment approach not only killed both gram-negative and gram-positive bacteria but also effectively treated bacterial infections (abscesses and osteomyelitis). Moreover, Mg2+ released from the Mg rods enhanced and accelerated the process of bone osteogenesis. Overall, our work cleverly exploited the eddy-thermal effect and chemical activity of Mg implants under AMFs, aiming to eliminate the inflammatory environment and combat bacterial infections by the simultaneous release of H2, OH−, and Mg2+, thereby facilitating tissue regeneration. This therapeutic strategy achieved multiple benefits in one, thus presenting a promising avenue for clinical application.

Osteosarcoma (OS) patients have a poor prognosis due to its high degree of heterogeneity and high rate of metastasis. Magnetic hyperthermia therapy (MHT) combined with immunotherapy is an effective strategy to treat solid and metastatic tumors. Here, we combined biodegradable magnesium (Mg) macroscale rods, which acted as an eddy thermo-magnetic agent under a low external alternating magnetic field, and immunotherapy to achieve a radical cure for OS. The eddy thermal effect (ETE) of the Mg rods (MgR) showed outstanding cytotoxic effects and enhanced the maturation of dendritic cells (DCs), and the mild MHT induced the immunogenic cell death (ICD) in the OS cells. Combined with immune checkpoint blockade (ICB) therapy, we obtained an excellent curative effect against OS, and a further evaluation demonstrated that the local MHT induced by the MgR increased T cells infiltration and the polarization of M1 macrophages. Interestingly, the biodegradable MgR also promoted bone osteogenesis. Our work highlighted the uneven ETE mediated by the biodegradable MgR induced a comprehensive immunologic activation in the OS tumor microenvironment (TME), which would inspire the application of MHT for the effective treatment of OS.

Oxidative stress, due to the disruption of the balance between reactive oxygen species (ROS) generation and the antioxidant defense system, plays an important role in the pathogenesis of rheumatoid arthritis (RA). Excessive ROS leads to the loss of biological molecules and cellular functions, release of many inflammatory mediators, stimulate the polarization of macrophages, and aggravate the inflammatory response, thus promoting osteoclasts and bone damage. Therefore, foreign antioxidants would effectively treat RA. Herein, ultrasmall iron-quercetin natural coordination nanoparticles (Fe-Qur NCNs) with excellent anti-inflammatory and antioxidant properties were constructed to effectively treat RA. Fe-Qur NCNs obtained by simple mixing retain the inherent ability to remove ROS of quercetin and have a better water-solubility and biocompatibility. In vitro experiments showed that Fe-Qur NCNs could effectively remove excess ROS, avoid cell apoptosis, and inhibit the polarization of inflammatory macrophages by reducing the activation of the nuclear factor-κ-gene binding (NF-κB) pathways. In vivo experiments showed that the swollen joints of mice with rheumatoid arthritis treated with Fe-Qur NCNs significantly improved, with Fe-Qur NCNs largely reducing inflammatory cell infiltration, increasing anti-inflammatory macrophage phenotypes, and thus inhibiting osteoclasts, which led to bone erosion. This study demonstrated that the new metal-natural coordination nanoparticles could be an effective therapeutic agent for the prevention of RA and other diseases associated with oxidative stress.

Bacterial fruit blotch, caused by seed-borne pathogen Acidovorax citrulli, poses a serious threat to the production of cucurbits globally. Although the disease can cause substantial economic losses, limited information is available about the molecular mechanisms of virulence. This study identified that, a random transposon insertion mutant impaired in the ability to elicit a hypersensitive response on tobacco. The disrupted gene in this mutant was determined to be Aave_0638, which is predicted to encode a YggS family pyridoxal phosphate-dependent enzyme. YggS is a highly conserved protein among multiple organisms, and is responsible for maintaining the homeostasis of pyridoxal 5′-phosphate and amino acids in cells. yggS deletion mutant of A. citrulli strain XjL12 displayed attenuated virulence, delayed hypersensitive response, less tolerance to H2O2 and pyridoxine, increased sensitivity to antibiotic β-chloro-D-alanine, and reduced swimming. In addition, RNA-Seq analysis demonstrated that yggS was involved in regulating the expression of certain pathogenicity-associated genes related to secretion, motility, quorum sensing and oxidative stress response. Importantly, YggS significantly affected type III secretion system and its effectors in vitro. Collectively, our results suggest that YggS is indispensable for A.citrulli virulence and expands the role of YggS in the biological processes.

Abstract Background An inappropriate anastomosis method during laparoscopic anterior rectal resection can increase the risk of anastomotic complications and affect surgical, economic, and oncological outcomes. The aim of this study is to compare the incidence of anastomotic complications and the surgical, economic, and oncological outcomes following single versus double purse-string anastomosis during laparoscopic total mesorectal excision (TME) for low rectal cancer. Methods/design This randomized controlled trial (the SINGLE–DOUBLE study) will randomly assign middle and low rectal adenocarcinoma patients to receive either single or double purse-string anastomosis during laparoscopic low anterior rectal resection. Patients will be eligible for inclusion only if they (1) have adenocarcinoma confirmed by preoperative colonoscopy and biopsy, (2) have a tumor situated less than 12 cm from the anal verge, (3) do not have the anal sphincter involved, and (4) do not have distant metastases. The primary endpoint measure will be the incidence of anastomotic complications (leakage, narrowing, and bleeding). The secondary endpoints will be surgical, economic, and oncological outcomes. A total of 500 patients will be enrolled in the study. Sample size calculation was based on previous reports and our retrospective analysis. Discussion This randomized single-center controlled trial is expected to demonstrate which anastomosis method (single or double purse-string anastomosis) is better for reducing complications and improving prognosis in rectal cancer patients undergoing laparoscopic TME for low or middle rectal cancer. Trial registration Registration number: ChiCTR1800016116. Protocol Registration Receipt: May 13, 2018.

In previous studies, two conflicting conclusions existed, which were: (a) the isobutane/n-butane ratio of natural gas increases with the increasing maturity (R o ) of source rocks and (b) decreases with the increasing R o . In this paper, the correlations between the isobutane/n-butane ratios, dryness of natural gases, and the R o values of source rocks of 77 gas samples from Cretaceous and Tertiary in Kuqa Depression, Tarim Basin, Triassic Xujiahe Formation in central Sichuan Basin, Carboniferous–Permian in Sulige and Yulin gas field, Ordos Basin, China, and 80 shale gas samples from Mississippian Barnett Shale in the Fort Worth Basin, the United States are analyzed to reveal the evolution of the isobutane/n-butane ratios, then mathematical models of the isobutane/n-butane ratios and R o are attempted to be established. Results show that the isobutane/n-butane ratio initially increases and then decreases with increasing R o , both coal-derived gas and oil-type gas. Diverse types of kerogens may be responsible for the different corresponding R o values when the isobutane/n-butane ratios of gases reach their maximum values. The initial increase in the isobutane/n-butane ratios with increasing R o is the reason that isobutane is mainly generated at a higher rate by carbonium ion reaction of α-olefins with protons during kerogen primary cracking at lower maturity, whereas free radical reactions to form n-butane relatively quickly during oil cracking at higher maturity and isobutane cracked at a higher rate during the wet gas cracking stage may result in the terminal decreases in the isobutane/n-butane ratios. Besides, mathematical models of the isobutane/n-butane ratios of different types of natural gas and maturity are established. Therefore, the maturity of gas source rock can be obtained quickly based on the models using the isobutane/n-butane ratio combined with other component information (such as dryness, wetness, etc.), which is of great significance to the characterization of natural gas maturity and gas source rock correlation.

Background/Aims: Increased expression of galectin-1 (Gal-1) in gastric cancer (GC) promotes metastasis and correlates with poor prognosis. The mechanisms by which Gal-1 promotes GC metastasis remain unknown. Methods: Gal-1and Sphingosine-1-phosphate receptor 1 (S1PR1) were determined by immunohistochemistry(IHC) and quantitative real time polymerase chain reaction (qRT-PCR) in GC specimens. Stably transfected Gal-1 or S1PR1 into SGC7901 and MGC-803 cells, western blot and invasion assays in vitro and nude mice tumorigenicity in vivo were also employed. Results: Overexpression of Gal-1 enhanced expression of S1PR1 in SGC-7901 cells, and increased cell invasion, while knockdown Gal-1 in MGC-803 cells reduced S1PR1 expression and diminished invasion. Simultaneous knockdown of Gal-1 and overexpression of S1PR1 in MGC803 cells rescued invasive ability of MGC803 cells. S1PR1 was associated with expression of epithelial-to-mesenchymal transition (EMT) markers in vitro and in clinical samples. EMT induced in MGC-803 cells by TGF-β1 was accompanied by S1PR1 activation, while knockdown of S1PR1 reduced response to TGF-β1, suggest that Gal-1 promotes GC invasion by activating EMT through a S1PR1-dependent mechanism. Overexpression of S1PR1 promoted subcutaneous xenograft growth and pulmonary metastases, and enhanced expression of EMT markers. Conclusion: Galectin-1 promotes metastasis in gastric cancer through a S1PR1- dependent mechanism, our results indicate that targeting S1PR1 may be a novel strategy to treat GC metastasis.

In the past three decades, about 0.93% of people moved from rural areas to cities per year in China. Therefore, understanding of the relationships among urban physical environment (UPE), economic development, and population growth are significant for China to realize sustainable urban development. Based on the concept and connotation of UPE and ecocity, the UPE evaluation system was constructed containing 6 first-level of indicators (i.e., climate, quality of ambient air and atmosphere, freshwater, wastewater, built environment, and noise pollution) and 13 second-level indicators. An entropy weight-TOPSIS model was developed in order to evaluate the UPE system, using the data of China’s 36 main cities from 2003 to 2016. The coupling coordination degree (CCD) among the UPE, economy, and population was measured by a ternary CCD model. The results showed that (1) the UPE of 36 main cities showed periodic fluctuations throughout the 14 years, and the coastal cities and southern cities had superior UPE than the inland cities and northern cities, respectively; (2) the vast majority of cities’ CCD had experienced steady upward trends. UPE, economy, and population promoted mutually in most of the cities, but in a few super cities, the economic development and population growth exceeded the capacity of UPE. Meanwhile, the CCD gaps between the northern and southern cities were significantly widened.

Blue Rubber Bleb Nevus Syndrome (BRBNS) is an uncommon congenital disorder characterized by sporadic venous malformation which mainly occurs in skin and alimentary canal. Here, we report a BRBNS patient with concomitant intestinal intussusception who diagnosed by intraoperative endoscopy and ultimately managed using surgical resection. A 19-year-old boy was referred to urgent surgery for acute melena and stomachache. He had used to be a long-term iron user for undiagnosed chronic anemia and papules. Abdominal CT on admission demonstrated the presence of intestinal intussusception. The following exploratory laparotomy and intraoperative endoscopy revealed multiple gastrointestinal hemangiomas. The postoperative course was uneventful and pathological examination certified multiple cavernous hemangiomas in the resected gastrointestines.