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The synthesis of chloramphenicol, a kind of amphenicol antibiotic with broad-spectrum antibacterial activity, is challenging due to its stereochemistry. Here, we have designed a four-step chemoenzymatic strategy, including a biocatalytic step mediated by l-threonine transaldolase from Pseudomonassp. (PsLTTA) to convert 4-nitrobenzaldehyde (1) to (2S,3R)-2-amino-3-hydroxy-3-(4-nitrophenyl)propanoic acid (2) followed by a three-step chemical reaction to obtain chloramphenicol. A rational design of PsLTTA was devised by reshaping the substrate binding pocket and substrate access channel, resulting in the best variant PsLTTA-N35A/C57I/F59A/H69F (PsLTTA-Mu9), which achieved a 7.1-fold higher yield of 2than wild-type PsLTTA. After coupling with ScADH/CbFDH to remove the byproduct acetaldehyde and optimizing the reaction conditions, the whole-cell catalyst BL21(PsLTTA-Mu9/ScADH/CbFDH) could synthesize 200 mM of 2in four hours with 99% conversion and 97.7% de, delivering the highest time–space yield (11.3 g L−1h−1) ever reported. Finally, the chemoenzymatic approach was applied for the gram-scale synthesis of 5with a high overall yield (54%). The success of this strategy demonstrates the great advantage of the chemoenzymatic approach in the asymmetric synthesis of chloramphenicol and may contribute to its industrial synthesis.

Background and aims: Esophageal stricture is a distressing issue for patients with early esophageal cancer following extensive endoscopic submucosal dissection (ESD), and the current steroid-based approaches are unsatisfactory for stricture prophylaxis. We evaluated the efficacy of oral hydrocortisone sodium succinate and aluminum phosphate gel (OHA) for stricture prophylaxis after extensive ESD. Methods: Patients undergoing > 3/4 circumferential ESD were randomized to either the endoscopic loco-regional triamcinolone acetonide injection (ETI) plus oral prednisone group or the OHA group. The primary endpoint was incidence of esophageal stricture, and the secondary endpoints included adverse events (AEs) and endoscopic balloon dilations (EBDs). Results: The incidence of esophageal stricture in OHA group (per-protocol analysis, 9.4%, 3/32; intention-to-treat analysis, 12.1%, 4/33) was significantly less than that of control group (per-protocol analysis, 35.5%, 11/31, P= 0.013; intention-to-treat analysis, 39.4%, 13/33, P= 0.011). Two sessions of EBD were necessary to release all strictures in the OHA group, while the similar EBDs (median 2, range 1–4) for 11 of the control. Operation-related AEs included infection (control vs. OHA group = 9.7% vs. 31.3%, P= 0.034), operation-related hypokalemia (19.4% vs. 31.3%, P= 0.278), perforation (3.2% vs. 3.1%), post-ESD hemorrhage (6.5% vs. 0%), and cardiac arrhythmia (0% vs. 6.3%). Steroid-related AEs included steroid-related hypokalemia (16.1% vs. 25%) and bone fracture (3.2% vs. 0%). Multivariate logistic regression analysis demonstrated that OHA was an independent protective factor for stricture (OR 0.079; 95%CI 0.011, 0.544; P= 0.01) and mucosal defect > 11/12 circumference was an independent risk factor (OR 49.91; 95%CI 6.7, 371.83; P< 0.001). Conclusions: OHA showed significantly better efficacy in preventing esophageal stricture after > 3/4 circumferential ESD compared to ETI plus oral prednisone.

Normal cells must overcome multiple protective mechanisms to develop into cancer cells. Their new capabilities include self-sufficiency in growth signals and insensitivity to antigrowth signals, evasion of apoptosis, a limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis; these are also termed the six hallmarks of cancer. A deep understanding of the genetic and protein alterations involved in these processes has enabled the development of targeted therapeutic strategies and clinical trial design in the search for ovarian cancer treatments. Clinically, significantly longer progression-free survival has been observed in the single use of PARP, MEK, VEGF and Chk1/Chk2 inhibitors. However, the clinical efficacy of the targeted agents is still restricted to specific molecular subtypes and no trials illustrate a benefit in overall survival. Exploring novel drug targets or combining current feasible biological agents hold great promise to further improve outcomes in ovarian cancer. In this review, we intend to provide a comprehensive description of the molecular alterations involved in ovarian cancer carcinogenesis and of emerging biological agents and combined strategies that target aberrant pathways, which might shed light on future ovarian cancer treatment.

For the characteristics of semi-rigid base asphalt pavement prone to cracking, various stress-absorption layers are applied widely by decreasing stress concentration, improving interlayer bonding and waterproofing. Existing studies on the anti-cracking effect of stress absorbing layers rarely consider top-down fatigue cracking on the outside of the boundary of the vehicle loading zone. Firstly, this paper proposes a finite element model setting a downward expansion of fatigue crack in pavement based on fracture mechanics. The influence law of modulus and thickness of stress absorbing layer on stress intensity factor of crack tip and the fatigue life of the pavement is analyzed furthermore. Numerical calculation results demonstrate that shearing stress intensity factor increases with stress absorbing layer thickness and decreases with stress absorbing layer modulus, while fatigue life of pavement grows with the modulus of the stress absorbing layer and decreases with its thickness. Sensitivity analysis indicates that the modulus of the stress absorbing layer has a greater effect on the fatigue life of the pavement relative to thickness, which offers reference for further promotion and application of stress absorbing layer.

Background: Carbapenem-resistant Acinetobacter baumannii (A. baumannii) was on the top of the list of the most threatening bacteria published by the WHO in 2017. Antisense oligonucleotides (ASOs) based therapy is a promising strategy for combating Multi-Drug Resistant (MDR) bacteria because of its high specificity, easy design and lower induction of resistance, but poor cellular uptake by bacteria has restricted the further utilization of this therapy. Methods: Here, we used CADY, a secondary amphipathic peptide of 20 residues that could successfully carry siRNA into mammalian cells, to prepare CADY/ASOs nanoparticles (CADY-NPs) targeting acpP (encoding acyl carrier protein), and evaluated the uptake features, the inhibitory effects of CADY-NPs on gene expression and the growth of MDR-A. baumannii. Results: We found that CADY-NPs could be quickly internalized by drug-sensitive and MDR-A. baumannii in an energy independent manner, which could be restrained by chlorpromazine (an inhibitor of clathrin mediated endocytosis) significantly. In addition, CADY-NPs targeting acpP concentrationdependently retarded the growth of MDR-A. baumannii, which was associated with the decreased expression of targeted genes in A. baumannii. Conclusion: In conclusion, our research is the first to demonstrate that CADY can deliver ASOs into bacteria and provide a novel strategy for the treatment of MDR-A. baumannii.

This exploratory study investigated the circumstances of falls and fall-related injuries among frail elderly people under home care. A convenience sample of 500 frail elderly (60–99 years old) from the Wanshoulu and Yuyuantan communities in Beijing's Haidian District during February 2013 and March 2014. Fall circumstances and related injuries were characterized by detailed interviews and questionnaires. The article reports the results of a study that the overall fall incidence was 41.5%, and higher for females than males. Falls mainly occurred in individuals who were over 80 years old (50.0%) and indoors (67.9%). The percentage of subjects who experienced a combined injury after the fall was 56.3%, whereas 19.0% fell causes a fracture. Approximately 35% of the subjects were hospitalized, and 27.6% of the subjects recovered more than 30 days. Results indicate that, falls in the frail elderly caused serious damage, and fall-related circumstances should be a great concern in this population.

The intended data-flow in a vulnerable program is subject to be subverted by attacks which exploit buffer overflows or format string vulnerabilities to write data to unintended location. In Mobile Telecommunication it is especially important on data safety. These attacks can be classified into two types: control-flow-attacks exploit buffer overflows or other vulnerabilities to overwrite a return address, a function pointer, or some other piece of control-data; non-control-data attacks exploit similar vulnerabilities to overwrite security critical data without subverting the intended control-flow in the program. The control-flow attacks are well studied and widely used, so there are several typical approaches to prevent them, which monitor the sequence of system calls emitted by the application being monitored and utilize control-flow information of the system calls for intrusion detection. However, the non-control-data attacks are rare for the reason that they rely on specific semantics of the target applications, and there are only few works that defend them to some extent. In order to prevent non-control-data attacks, we leverage dynamic taint technique to track the instruction level relationship between different system call arguments and construct taint graph which can represent behavior profile of a benign program in this paper..

Esophageal fibrovascular polyp is rare in esophageal neoplasms and usually very large. Here, we present a case of giant esophageal fibrovascular polyp. The patient had dysphagia and choking sensation at presentation. She underwent positron emission-computed tomography (PET-CT), endoscopy, endoscopic ultrasonography, and fine needle aspiration. She was clinically diagnosed as having an esophageal benign tumor and underwent endoscopic submucosal dissection. The polyp was successfully resected; however, the process was very difficult, and the lesion was too large to pass through the upper esophagus. Finally, we removed the lesion surgically. Fibrovascular polyps are often large, and if endoscopic resection is chosen, it is necessary to consider the difficulties that may be encountered during resection, before initiating treatment.

Esophageal tuberculosis is rare among digestive system diseases. We herein present two cases of esophageal tuberculosis. One patient presented with a choking sensation and pain in the chest, and the other presented with loss of appetite and emaciation. Both patients had an esophagomediastinal fistula, underwent endoscopic ultrasonography and fine-needle aspiration, were clinically diagnosed with esophageal tuberculosis, received antituberculosis treatment, and exhibited clinical improvement. These two rare cases suggest that the possibility of esophageal tuberculosis should be considered in patients with an esophagomediastinal fistula. Endoscopic ultrasonography and fine-needle aspiration can be performed to assist the diagnosis. Good clinical results can often be achieved with timely antituberculosis treatment.

Objective Endoscopic submucosal dissection (ESD) is widely used in early-stage esophageal cancer, but the quality of life of patients with postoperative stricture is markedly reduced, requiring long-term repeat, periodic endoscopic balloon dilatation. We evaluated the combination of hydrocortisone sodium succinate and aluminum phosphate gel administered orally for stricture prevention.Methods We retrospectively assigned 27 patients who underwent ≥3/4 circular ESD for esophageal superficial squamous cell cancer to one of two groups according to the preventative strategy: endoscopic intralesional steroid injection and systemic steroid (IT+ST group) and oral combination of hydrocortisone sodium succinate and aluminum phosphate gel (OHA group). Stricture rate was compared between the two groups.Results There were six and seven complete and ≥3/4 circular ESD cases, respectively, in the IT+ST group and four and ten cases in the OHA group. Stricture rates in the IT+ST and OHA groups were 53.8% and 7.1%, respectively. Nine patients in each group developed hypokalemia after glucocorticoid administration.Conclusions OHA is a promising treatment strategy for stricture prevention following large-circumference ESD in patients with early stage esophageal carcinoma.