A Novel Transferable Resistance-Nodulation-Division Pump Gene Cluster, tmexCD2-toprJ2, Confers Tigecycline Resistance in Raoultella ornithinolytica.

We recently identified a novel plasmid-mediated resistance-nodulation-division (RND)-type efflux pump gene cluster, tmexCD1-toprJ1, in Klebsiella pneumoniae that conferred resistance to multiple antimicrobials, including tigecycline. While homologs of tmexCD1-toprJ1 were found encoded in many other bacterial species in GenBank, their functions and transfer mechanisms remain unknown. This study identified another mobile gene cluster, tmexCD2-toprJ2, co-occurring on both a plasmid (pHNNC189-2) and the chromosome of a clinical Raoultella ornithinolytica isolate, strain NC189, producing KPC-2, NDM-1, and RmtC. tmexCD2-toprJ2 shares high similarity at the nucleotide level with tmexCD1-toprJ1, with 98.02%, 96.75%, and 99.93% identities to tmexC1, tmexD1, and toprJ1, respectively. Phylogenetic analysis revealed that tmexCD2-toprJ2 may have originated from the chromosome of a Pseudomonas species. The expression of tmexCD2-toprJ2 in an Escherichia coli strain resulted in an 8-fold increase in the tigecycline MIC and decreased susceptibility to other antimicrobials. Genetic context analyses demonstrated that tmexCD2-toprJ2, together with the adjacent hypothetical site-specific integrase genes, was possibly captured and mobilized by a XerD-like tyrosine recombinase system, forming a putative transposition unit (xerD-like-int3-like-thf2-ybjD-umuD-ΔumuC1-int1-like-int2-like-hp1-hp2-tnfxB2-ISBvi2-tmexCD2-toprJ2-ΔumuC1), which was inserted into umuC-like genes in both the NC189 plasmid pHNNC189-2 and the chromosome. Since tmexCD1-toprJ1 and tmexCD2-toprJ2 could confer multidrug resistance, the spread of these gene clusters, associated with the new recombinase system, calls for more attention.

The impact on quality of life from informing diagnosis in patients with cancer: a systematic review and meta-analysis.

BACKGROUND: The aim of this study was to assess the impact on quality of life from informing patients with cancer of their diagnosis and disease status. METHOD: We searched the follow databases, PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), PsycINFO, WEB OF SCIENCE, Embase, CBM (Chinese Biomedical Literature database), WANFANG database (Chinese Medicine Premier), and CNKI (China National Knowledge Infrastructure), using the following terms: neoplasm, cancer, tumor, tumor, carcinoma, disclosure, truth telling, breaking bad news, knowledge, knowing, awareness, quality of life, QOL. Pairs of reviewers independently screened documents and extracted the data, and the meta-analysis was performed using Revman 5.0 software. RESULTS: Eleven thousand seven hundred forty records retrieved from the databases and 23 studies were included in the final analysis. A meta-analysis revealed that there were no differences in either the general quality of life and symptoms of fatigue, pain, dyspnea, insomnia, appetite loss, and diarrhea, between informed and uniformed cancer patients (P > 0.05). There were also no differences found between the patient groups in physical function, role function, cognitive activity, and emotional function (P > 0.05). In terms of vitality, patients who were completely informed about their diagnosis showed higher vitality than uniformed patients. Uninformed patients seemed to have lower social function scores. Between partly informed and uninformed cancer patients, no differences were found in their general quality of life, function domains, and disease-related symptoms (P > 0.05). CONCLUSION: Informing cancer patients of their diagnosis may not have a detrimental effect on their quality of life. TRIAL REGISTRATION: CRD42017060073 .

Rapid Increase in Carbapenemase-Producing Enterobacteriaceae in Retail Meat Driven by the Spread of the blaNDM-5-Carrying IncX3 Plasmid in China from 2016 to 2018.

The presence and molecular characteristics of carbapenemase-producing Enterobacteriaceae (CPE) among meat products in China were investigated. A total of 110 carbapenem-resistant Enterobacteriaceae (CRE) isolates, including 94 Escherichia coli and 10 Klebsiella pneumoniae isolates, were identified from 105 of 794 (13.2%) samples. The positive rates markedly increased from 2016 (9.4%) to 2018 (22.2%). Only blaNDM genes were detected; 79.1% of blaNDM genes were carried by IncX3 plasmids. Routine monitoring of carbapenemase-producing Enterobacteriaceae in the animal food supply is highly recommended.

Organocatalytic Redox Deracemization of Cyclic Benzylic Ethers Enabled by An Acetal Pool Strategy.

The first redox deracemization of a series of cyclic benzylic ethers, including 6H-benzo[c]chromenes, isochromans, and 1H-isochromenes, is described. An "acetal pool" strategy was adopted to harmonize the complete oxidation of secondary ethers with imidodiphosphoric acid catalyzed asymmetric transfer hydrogenation. The synthetic utility of the process was demonstrated by the effective deracemization of biologically active molecules of interest that are difficult to prepare by other methods.

TBHP/TFA mediated oxidative cross-dehydrogenative coupling of N-heterocycles with aldehydes.

An effective and metal-free oxidative cross-dehydrogenative coupling (CDC) of N-heterocycles with diverse aldehydes has been established in the presence of TBHP/TFA. The scope with respect to aldehyde and N-heterocycle components is broad, allowing facile synthesis of a broad range of structurally diverse C1-acyl substituted heterocycles in good efficiency.

Preparation and Characterization of Puerarin-Loaded Lipid Nanocapsules.

The puerarin-loaded lipid nanocapsules (PUE-LNCs), composed of labrafac, lipoid and water, were prepared with a phase inversion procedure. The formulation was optimized by simplex lattice design and characterized for its size, zeta potential and in vitro drug release. The results showed that the PUE-LNCs performed a homogeneous typical core-shell structure under transmission electron microscope (TEM). The entrapment efficiency and drug loading were 56.61 ± 0.27% and 2.62 ± 0.12%, respectively. In vitro drug release revealed the PUE-LNCs showed a controlled-release manner in both artificial simulated gastric juice (pH 1.0) and artificial simulated intestinal fluid (pH 6.8). Based on the aforementioned results, it should now allow a promising tuning for further applications of LNCs as a drug delivery system for puerarin.

Practical and highly selective C-H functionalization of structurally diverse ethers.

A trityl ion mediated C-H functionalization of ethers with a wide range of nucleophiles at ambient temperature has been developed. The reaction displays high chemoselectivity and good functional group tolerance. The protocol also exhibits excellent regio- and diastereoselectivities for the unsymmetric ethers, thus stereoselectively generating highly functionalized disubstituted 2,5-trans tetrahydrofurans (THF), 2,6-trans tetrahydropyrans (THP), 2,6-trans dihydropyrans (DHP), and 1,3-trans isochromans, and highlighting the capacity of the protocol in complex molecule synthesis.

The impact of epidemic infectious diseases on the relationship between subjective well-being and social class identity in older adults: The mediating role of Self-rated health.

BACKGROUND: The purpose of this paper is to explore the relationship between subjective well-being, social class identity, and Self-rated health among older persons,. Focusing on the mediating role of health and the impact of epidemic infectious diseases on these relationships. METHODS: Based on the 2018 and 2021 China General Social Survey (CGSS) databases, the data were screened, and processed. Using Stata17, we employed ordered probit regression to examine the relationships among variables and Bootstrap methods to assess mediation effects, and the CGSS data for 2018 and 2021 were compared and analyzed. RESULTS: Our results revealed that factors such as social class identity, health status, and personal income significantly positively impact older persons' subjective well-being (P<0.01). Notably, there was a partial mediating effect of health status between the subjective well-being of the elderly and social class identity. And findings showed that when older adults were affected by epidemic diseases, their subjective well-being, social class identity, and Self-rated health remained significantly positively correlated. Subjective well-being, social class identity. What is more noteworthy is that when affected by epidemic infectious diseases, older adults' subjective well-being, social class identity, and Self-rated health remained significantly positively correlated. The mediating role of self-rated health in older adults' subjective well-being and social class identity increased from 9.6% to 12.4%. CONCLUSIONS: In the face of epidemic infectious diseases, we need to pay more attention to the Self-rated health of the elderly, and the Chinese government should take effective measures to improve their health level, which will in turn improve the subjective well-being of the elderly and realize the goal of healthy aging.

Insights into the enhancement mechanism of immersion resistance of cooked noodles induced by wheat flour post-ripening: The view from protein cross-linking.

To overcome the problem that takeaway noodles possessed poor immersion resistance, in this study noodles were prepared from post-ripened wheat flour, and changes in textural properties, protein components, and water status of noodles were determined. The firmness and tensile distance of noodles were gradually increased by 7.40%-35.88% when wheat flour was post-ripened for 20-40 d. Afterwards, noodle textural qualities were slightly decreased. Compared with control groups, contents of glutenin macropolymer (GMP) and disulfide bonds were significantly (p<0.05) increased and protein network was also more compact, whereas the Glutenin/Gliadin ratio and free sulfhydryl groups content were significantly (p<0.05) reduced. Contents of sodium dodecyl sulfate extractable protein (SDSEP) were reduced by 3.22%-6.23%. Meanwhile, the decrease in A23 indicated that wheat flour post-ripening limited water-absorbing capacity of noodles during immersion. In conclusion, wheat flour post-ripening promoted the immersion resistance of noodles by inducing protein cross-linking, and the best post-ripening time was 20-40 d.

Giant Ulcer with Necrosis on Right Vulva, Groin, and Thigh-- A Case of Necrotizing Fasciitis Associated with Erythematous Pemphigus.

Necrotizing fasciitis is a rare, severe, rapidly progressing disease with a high mortality rate. We report a case of a 72-year female with erythematous pemphigus who developed erythema, swelling and ulceration on right vulva, groin, and thigh. The early clinical manifestations of the patient were nonspecific and easily misdiagnosed as cellulitis. However, upon the occurrence of ulceration and necrosis, deep fungal infection, pyoderma gangrenosum or lymphoproliferative disorders were considered. The pathology suggested IgG4-related diseases, plasmacytoma et al. But at last, surgical exploration and postoperative pathology confirmed the diagnosis of necrotizing fasciitis. The patient recovered after multiple aggressive surgical debridement procedures and antibiotic therapy and the patient has been followed up for 2 years without recurrence. Clinicians should be vigilant about the possibility of necrotizing fasciitis in patients with erythema, pain, rapid ulceration of skin and soft tissue, particularly in immunocompromised individuals with long-term use of immunosuppressive agents. It is crucial for saving life by early multi-disciplinary consultation, prompt diagnosis, and aggressive treatment.

Persistence and molecular epidemiology of blaNDM-positive Gram-negative bacteria in three broiler farms: A longitudinal study (2015-2021).

Although carbapenems have not been approved for animal use, blaNDM-positive bacteria (NPB) are increasingly being detected in farm animals. It is important to investigate the routes and underlying mechanisms of evolution and transmission of animal-borne NPB. In this study, NPB recovered from chicken feces and environmental samples in three adjacent broiler farms were investigated. We found that 13.0% of Escherichia coli strains recovered from chicken feces during the period 2015-2016 carried the blaNDM gene. In 2017-2021, however, as many as 55.8% chicken and environmental samples collected during the breeding period were found to harbor NPB. Importantly, such strains were detectable in samples from farmland (10.3%, 8/78), vegetable fields (7.3%, 3/41), and environment of chicken farms (25.6%, 41/160) which had been left vacant for a long period of time. Intriguingly, different sequence types of NPB became dominant in different years. Both clonal dissemination of NPB and horizontal transmission of blaNDM-bearing plasmids were observed among different farms and among the environment niches inside and outside the farm houses. Worryingly, transmission of NPB and blaNDM-bearing plasmids between these farms and other places was also observed. All in all, our results suggested the persistence of NPB in chickens and farm environments, presumably due to extensive contamination by exogenous materials and transmission of NPB within the farm system. These events were aggravated by the increase in antibiotic usage and poor sanitary conditions in the farm houses. Stringent control measures should be implemented to arrest transmission of animal-borne NPB to the environment and the community.

Fabrication of localized surface plasmon resonance fiber probes using ionic self-assembled gold nanoparticles.

An nm-thickness composite gold thin film consisting of gold nanoparticles and polyelectrolytes is fabricated through ionic self-assembled multilayers (ISAM) technique and is deposited on end-faces of optical fibers to construct localized surface plasmon resonance (LSPR) fiber probes. We demonstrate that the LSPR spectrum induced by ISAM gold films can be fine-tuned through the ISAM procedure. We investigate variations of reflection spectra of the probe with respect to the layer-by-layer adsorption of ISAMs onto end-faces of fibers, and study the spectral variation mechanism. Finally, we demonstrated using this fiber probe to detect the biotin-streptavidin bioconjugate pair. ISAM adsorbed on optical fibers potentially provides a simple, fast, robust, and low-cost, platform for LSPR biosensing applications.

An Initial Alignment Technology of Shearer Inertial Navigation Positioning Based on a Fruit Fly-Optimized Kalman Filter Algorithm.

The shearer is one of the core equipment of the fully mechanized coal face. The fast and accurate positioning of the shearer is the prerequisite for its memory cutting, intelligent height adjustment, and intelligent speed adjustment. Inertial navigation technology has many advantages such as strong autonomy, good concealment, and high reliability. The accurate positioning of the shearer based on inertial navigation can not only determine its operating position but also measure the direction of movement. However, when inertial navigation is used to locate the shearer in motion, the cumulative errors will occur, resulting in inaccurate positioning of the shearer. The accuracy of the initial alignment is directly related to the working precision of the inertial navigation system. In order to improve the efficiency and accuracy of initial alignment, an improved initial alignment method is proposed in this paper, which uses a fruit fly-optimized Kalman filter algorithm for initial alignment. In order to improve the filtering performance, the fruit fly-optimized Kalman filter algorithm uses an improved fruit fly algorithm to realize the adaptive optimization of system noise variance. Finally, simulation and experiments verify the effectiveness of the fruit fly-optimized Kalman filter algorithm.

Successful treatment of large cutaneous facial Rosai-Dorfman disease using combination of subtotal resection and ALA-PDT: A case report.

Rosai-Dorfman disease (RDD), also called sinus histiocytosis with massive lymphadenopathy, is a rare, benign and self-limited histiocytosis. We present a case of cutaneous Rosai-Dorfman disease (CRDD) on the right cheek that responded well to combination of subtotal resection and ALA-PDT. We believe that the combination of subtotal resection and ALA-PDT treatment for large cutaneous facial Rosai-Dorfman disease patients is a more effective, highly satisfying, and quick therapy worth promoting.

Identification of fosA10, a Novel Plasmid-Mediated Fosfomycin Resistance Gene of Klebsiella pneumoniae Origin, in Escherichia coli.

PURPOSE: Several subtypes of plasmid-mediated fosfomycin resistance gene fosA in Enterobacteriaceae have been reported worldwide and have caused concern. The present study characterized a novel member of fosA gene located on a plasmid from Escherichia coli. MATERIALS AND METHODS: A fosfomycin-resistant E. coli isolate PK9 was recovered from a chicken meat sample in 2018. The presence of fosA genes was detected by PCR and sequencing. Whole-genome sequencing (WGS), conjugation, and cloning were performed to identify the mechanism responsible for fosfomycin resistance. Oxford Nanopore MinION sequencing was carried out to characterize the plasmid carrying fosfomycin resistance gene and the genetic context of the novel fosA variant. RESULTS: A novel fosA gene with significant homology (>98%) with fosA6 and fosA5 genes was identified by WGS and was named fosA10. FosA10 shared 56.1% to 98.6% amino acid sequence identity with other reported plasmid-mediated FosA enzymes. Fosfomycin resistance and fosA10 gene were successfully transferred to E. coli C600 by conjugation. Cloning confirmed that FosA10 could confer fosfomycin resistance (MIC > 128 µg/mL). The fosA10 gene was localized on a 53kb IncFII (F35:A-:B-) plasmid. The ∆lysR-fosA10-∆hp fragment (4328 bp), located between two copies of IS10R, showed 100% identity with the chromosomal sequences of 17 Klebsiella pneumoniae strains of ST664 and one of ST3821 in GenBank. CONCLUSION: Our findings indicated that the fosA10 gene of E. coli might be captured from the chromosome of K. pneumoniae by IS10, which further demonstrated that K. pneumoniae might act as a reservoir of fosA-like genes acquired by E. coli.

Surgical interventions combined with photodynamic therapy in the treatment of Perifolliculitis Capitis Abscendens et Suffodiens: Report of 5 cases.

Perifolliculitis capitis abscedens et suffodiens (PCAS), also known as dissecting cellulitis of the scalp (DCS), is a rare, chronic, suppurative inflammatory disease of the scalp which may evolve into cicatricial alopecia. Its refractory nature has a detrimental impact on patients' quality of life. Here, we report five cases of PCAS treated with 5% 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT), prior to which different methods of surgical intervention were given. The surgical interventions were under local anesthesia. In general, all surgical interventions, pretreatments and PDT were well tolerated. 4 patients showed complete clearance of lesions and 1 patient attained significant improvement of symptoms 1 month after treatment. This suggested that surgical interventions, combined with topical ALA-PDT could be an effective, minimally-invasive, and safe alternative for PCAS, especially for cases recalcitrant to other conventional therapies.

Frequency-Specific Changes of Resting Brain Activity in Parkinson's Disease: A Machine Learning Approach.

The application of resting state functional MRI (RS-fMRI) in Parkinson's disease (PD) was widely performed using standard statistical tests, however, the machine learning (ML) approach has not yet been investigated in PD using RS-fMRI. In current study, we utilized the mean regional amplitude values as the features in patients with PD (n = 72) and in healthy controls (HC, n = 89). The t-test and linear support vector machine were employed to select the features and make prediction, respectively. Three frequency bins (Slow-5: 0.0107-0.0286 Hz; Slow-4: 0.0286-0.0821 Hz; conventional: 0.01-0.08 Hz) were analyzed. Our results showed that the Slow-4 may provide important information than Slow-5 in PD, and it had almost identical classification performance compared with the Combined (Slow-5 and Slow-4) and conventional frequency bands. Similar with previous neuroimaging studies in PD, the discriminative regions were mainly included the disrupted motor system, aberrant visual cortex, dysfunction of paralimbic/limbic and basal ganglia networks. The lateral parietal lobe, such as right inferior parietal lobe (IPL) and supramarginal gyrus (SMG), was detected as the discriminative features exclusively in Slow-4. Our findings, at the first time, indicated that the ML approach is a promising choice for detecting abnormal regions in PD, and a multi-frequency scheme would provide us more specific information.

Emergence of a Plasmid-Encoded Resistance-Nodulation-Division Efflux Pump Conferring Resistance to Multiple Drugs, Including Tigecycline, in Klebsiella pneumoniae.

Transporters belonging to the chromosomally encoded resistance-nodulation-division (RND) superfamily mediate multidrug resistance in Gram-negative bacteria. However, the cotransfer of large gene clusters encoding RND-type pumps from the chromosome to a plasmid appears infrequent, and no plasmid-mediated RND efflux pump gene cluster has yet been found to confer resistance to tigecycline. Here, we identified a novel RND efflux pump gene cluster, designated tmexCD1-toprJ1, on plasmids from five pandrug-resistant Klebsiella pneumoniae isolates of animal origin. TMexCD1-TOprJ1 increased (by 4- to 32-fold) the MICs of tetracyclines (including tigecycline and eravacycline), quinolones, cephalosporins, and aminoglycosides for K.pneumoniae, Escherichia coli, and Salmonella TMexCD1-TOprJ1 is closely related (64.5% to 77.8% amino acid identity) to the MexCD-OprJ efflux pump encoded on the chromosome of Pseudomonas aeruginosa In an IncFIA plasmid, pHNAH8I, the tmexCD1-toprJ1 gene cluster lies adjacent to two genes encoding site-specific integrases, which may have been responsible for its acquisition. Expression of TMexCD1-TOprJ1 in E. coli resulted in increased tigecycline efflux and in K. pneumoniae negated the efficacy of tigecycline in an in vivo infection model. Expression of TMexCD1-TOprJ1 reduced the growth of E. coli and Salmonella but not K. pneumoniaetmexCD1-toprJ1-positive Enterobacteriaceae isolates were rare in humans (0.08%) but more common in chicken fecal (14.3%) and retail meat (3.4%) samples. Plasmid-borne tmexCD1-toprJ1-like gene clusters were identified in sequences in GenBank from Enterobacteriaceae and Pseudomonas strains from multiple continents. The possibility of further global dissemination of the tmexCD1-toprJ1 gene cluster and its analogues in Enterobacteriaceae via plasmids may be an important consideration for public health planning.IMPORTANCE In an era of increasing concerns about antimicrobial resistance, tigecycline is likely to have a critically important role in the treatment of carbapenem-resistant Enterobacteriaceae, the most problematic pathogens in human clinical settings-especially carbapenem-resistant K.pneumoniae Here, we identified a new plasmid-borne RND-type tigecycline resistance determinant, TMexCD1-TOprJ1, which is widespread among K. pneumoniae isolates from food animals. tmexCD1-toprJ1 appears to have originated from the chromosome of a Pseudomonas species and may have been transferred onto plasmids by adjacent site-specific integrases. Although tmexCD1-toprJ1 still appears to be rare in human clinical isolates, considering the transferability of the tmexCD1-toprJ1 gene cluster and the broad substrate spectrum of TMexCD1-TOprJ1, further dissemination of this mobile tigecycline resistance determinant is possible. Therefore, from a "One Health" perspective, measures are urgently needed to monitor and control its further spread. The current low prevalence in human clinical isolates provides a precious time window to design and implement measures to tackle this.