Genetic landscape of ESBL producing international clone ST410 of Escherichia coli from pediatric infections in Shenzhen, China.

Background: The emergence of ESBLs producing cephalosporin-resistant Escherichia coli isolates poses a threat to public health. This study aims to decipher the genetic landscape and gain insights into ESBL-producing E. coli strains belonging to the high-risk clone ST410 from pediatric patients. Methods: 29 E. coli ST410 isolates were collected from young children and subjected to antimicrobial susceptibility testing, Whole-genome sequencing (WGS), serotype analysis, MLST, ESBL genes, virulence genes, and plasmid profiling. Results: Antimicrobial susceptibility testing demonstrated a high level of resistance to cephalosporins followed by aminoglycoside, sulfonamide, carbapenem and penicillin group of antibiotics. However, n=20/29 shows MDR phenotype. Phylogenetic group B2 (n=15) dominated, followed by group D (n=7), group A (n=4), and group B1 (n=3). Serotyping analysis identified O1:H7 (n=8), O2:H1 (n=6), O8:H4 (n=5), O16:H5 (n=4), and O25:H4 (n=3). Other serotypes identified included O6:H1, O15:H5, and O18:H7 (n=1 each). The most commonly detected ESBL genes were bla CTX-M, (n=26), followed by bla TEM (n=23), and bla SHV (n=18). Additionally, bla OXA-1 (n=10), bla OXA-48 (n=5), bla KPC-2 (n=3), bla KPC-3 (n=2), bla NDM-1 (n=4), bla NDM-5 (n=1), bla GES-1 (n=2), bla GES-5 (n=1), and bla CYM-1 (n=3). Notable virulence genes identified within the ST410 isolates included fimH (n=29), papC (n=24), hlyA (n=22), and cnf1 (n=18), among others. Diverse plasmids were observed including IncFIS, IncX4, IncFIA, IncCol, IncI2 and IncFIC with transmission frequency ranges from 1.3X10-2 to 2.7X10-3. Conclusion: The ST410 clone exhibited a complex resistance profile, diverse serotypes, the presence of specific resistance genes (ESBL genes), virulence gene repertoire, and diverse plasmids. The bla CTX-M was the most prevalent ESBL gene detected.

Injectable Mechanophore Nanoparticles for Deep-Tissue Mechanochemical Dynamic Therapy.

Photodynamic therapy (PDT) and sonodynamic therapy (SDT), using nonionizing light and ultrasound to generate reactive oxygen species, offer promising localized treatments for cancers. However, the effectiveness of PDT is hampered by inadequate tissue penetration, and SDT largely relies on pyrolysis and sonoluminescence, which may cause tissue injury and imprecise targeting. To address these issues, we have proposed a mechanochemical dynamic therapy (MDT) that uses free radicals generated from mechanophore-embedded polymers under mechanical stress to produce reactive oxygen species for cancer treatment. Yet, their application in vivo is constrained by the bulk form of the polymer and the need for high ultrasound intensities for activation. In this study, we developed injectable, nanoscale mechanophore particles with enhanced ultrasound sensitivity by leveraging a core-shell structure comprising silica nanoparticles (NPs) whose interfaces are linked to polymer brushes by an azo mechanophore moiety. Upon focused ultrasound (FUS) treatment, this injectable NP generates reactive oxygen species (ROS), demonstrating promising results in both an in vitro 4T1 cell model and an in vivo mouse model of orthotopic breast cancers. This research offers an alternative therapy technique, integrating force-responsive azo mechanophores and FUS under biocompatible conditions.

Case report: Abscesses in children caused by invasive group A Streptococcus.

Streptococcus is one of the common pathogens of suppurative infections. Invasive group A Streptococcus (iGAS) infections often develop from skin or soft tissue infections, and streptococcal toxic shock syndrome is considered the main cause of death in Chinese children with iGAS infectious disease. However, soft tissue infections caused by iGAS infections, especially the formation of abscesses, are relatively rare. A retrospective study was conducted, and pediatric in-patients who were diagnosed with an iGAS infection identified by cultures from normally sterile sites and treated in a tertiary hospital during 2016-2018 were included. A total of 14 patients were identified, which included 10 boys and four girls. The patients had an age range from 3 months to 10 years and were diagnosed with soft tissue infections and a formation of abscesses caused by iGAS infections. The most common sites of infections were the lower limbs. In five patients, the abscess was accompanied by fever, and the local soft tissue showed redness, swelling, tenderness, and an elevated skin temperature. Laboratory findings included an increased white blood cell (WBC) count in 12 patients, an increased C reactive protein (CRP) level in seven patients, and an increased erythrocyte sedimentation rate (ESR) in 10 patients. No patients had an elevated procalcitonin level. For all 14 patients, we performed puncture and drainage of abscesses, and cultured GAS from the drainage fluid. All children also received antibiotic treatment. During 2 months of follow-up, the patients' condition remained stable and no evidence of kidney or heart damage was observed. For pediatric patients with abscesses, early diagnosis, prompt treatment with incision and drainage, and immediate culture of the drainage fluid are important. Upon confirmation of an iGAS infection, ß-lactam antibiotics should be given to provide effective treatment, and in some patients with poor therapeutic outcomes, the use of vancomycin as an alternative can achieve the desired results.

Adaptive loss-guided multi-stage residual ASPP for lesion segmentation and disease detection in cucumber under complex backgrounds.

BACKGROUND: In complex agricultural environments, the presence of shadows, leaf debris, and uneven illumination can hinder the performance of leaf segmentation models for cucumber disease detection. This is further exacerbated by the imbalance in pixel ratios between background and lesion areas, which affects the accuracy of lesion extraction. RESULTS: An original image segmentation framework, the LS-ASPP model, which utilizes a two-stage Atrous Spatial Pyramid Pooling (ASPP) approach combined with adaptive loss to address these challenges has been proposed. The Leaf-ASPP stage employs attention modules and residual structures to capture multi-scale semantic information and enhance edge perception, allowing for precise extraction of leaf contours from complex backgrounds. In the Spot-ASPP stage, we adjust the dilation rate of ASPP and introduce a Convolutional Attention Block Module (CABM) to accurately segment lesion areas. CONCLUSIONS: The LS-ASPP model demonstrates improved performance in semantic segmentation accuracy under complex conditions, providing a robust solution for precise cucumber lesion segmentation. By focusing on challenging pixels and adapting to the specific requirements of agricultural image analysis, our framework has the potential to enhance disease detection accuracy and facilitate timely and effective crop management decisions.

UV-assisted synthesis of ultra-small GO-Austar for efficient PTT therapeutic architectonic construction.

Conventional Au nanomaterial synthesis typically necessitates the involvement of extensive surfactants and reducing agents, leading to a certain amount of chemical waste and biological toxicity. In this study, we innovatively employed ultra-small graphene oxide as a reducing agent and surfactant for the in situ generation of small Au nanoparticles under ultraviolet irradiation (UV) at ambient conditions. After ultra-small GO-Au seeds were successfully synthesized, we fabricated small star-like Au nanoparticles on the surface of GO, in which GO effectively prevented Austar from aggregation. To further use GO-Austar for cancer PTT therapy, through the modification of reduced human serum albumin-folic acid conjugate (rHSA-FA) and loading IR780, the final probe GO-Austar@rHSA-FA@IR780 was prepared. The prepared probe showed excellent biocompatibility and superb phototoxicity towards MGC-803 cells in vitro. In vivo, the final probe dramatically increased tumor temperature up to 58.6 °C after 5 minutes of irradiation by an 808 nm laser, significantly inhibiting tumor growth and nearly eradicating subcutaneous tumors in mice. This research provides a novel and simple method for the synthesis of GO-Au nanocomposites, showcasing significant potential in biological applications.

Acne-induced pathological scars: pathophysiology and current treatments.

Acne is a common chronic inflammatory dermatosis that can lead to pathological scars (PSs, divided into hypertrophic scars and keloids). These kinds of abnormal scars seriously reduce the quality of life of patients. However, their mechanism is still unclear, resulting in difficult clinical prevention, unstable treatment effects and a high risk of recurrence. Available evidence supports inflammatory changes caused by infection as one of the keys to abnormal proliferation of skin fibroblasts. In acne-induced PSs, increasing knowledge of the immunopathology indicates that inflammatory cells directly secrete growth factors to activate fibroblasts and release pro-inflammatory factors to promote the formation of PSs. T helper cells contribute to PSs via the secretion of interleukin (IL)-4 and IL-13, the pro-inflammatory factors; while regulatory T cells have anti-inflammatory effects, secrete IL-10 and prostaglandin E2, and suppress fibrosis production. Several treatments are available, but there is a lack of combination regimens to target different aspects of acne-induced PSs. Overall, this review indicates that the joint involvement of inflammatory response and fibrosis plays a crucial role in acne-induced PSs, and also analyzes the interaction of current treatments for acne and PS.

Biomimetic-Membrane-Protected Plasmonic Nanostructures as Dual-Modality Contrast Agents for Correlated Surface-Enhanced Raman Scattering and Photoacoustic Detection of Hidden Tumor Lesions.

Optical imaging and spectroscopic modalities are of considerable current interest for in vivo cancer detection and image-guided surgery, but the turbid or scattering nature of biomedical tissues has severely limited their abilities to detect buried or occluded tumor lesions. Here we report the development of a dual-modality plasmonic nanostructure based on colloidal gold nanostars (AuNSs) for simultaneous surface-enhanced Raman scattering (SERS) and photoacoustic (PA) detection of tumor phantoms embedded (hidden) in ex vivo animal tissues. By using red blood cell membranes as a naturally derived biomimetic coating, we show that this class of dual-modality contrast agents can provide both Raman spectroscopic and PA signals for the detection and differentiation of hidden solid tumors with greatly improved depths of tissue penetration. Compared to previous polymer-coated AuNSs, the biomimetic coatings are also able to minimize protein adsorption and cellular uptake when exposed to human plasma without compromising their SERS or PA signals. We further show that tumor-targeting peptides (such as cyclic RGD) can be noncovalently inserted for targeting the ανß3-integrin receptors expressed on metastatic cancer cells and tracked via both SERS and PA imaging (PAI). Finally, we demonstrate image-guided resections of tumor-mimicking phantoms comprising metastatic tumor cells buried under layers of skin and fat tissues (6 mm in thickness). Specifically, PAI was used to determine the precise tumor location, while SERS spectroscopic signals were used for tumor identification and differentiation. This work opens the possibility of using these biomimetic dual-modality nanoparticles with superior signal and biological stability for intraoperative cancer detection and resection.

A clade of Streptococcus pneumoniae clonal complex 320 with increased tolerance to ß-lactam antibiotics in a Chinese metropolitan city.

OBJECTIVES: We characterized the population structure and features of clinical Streptococcus pneumoniae isolates associated with invasive pneumococcal disease (IPD) from 2009 to 2017 in a Chinese metropolitan city using a whole-genome sequencing approach. METHODS: Seventy-nine pneumococcal strains, including 60 serogroup-19 strains from children enduring IPD from a paediatric hospital in Shenzhen, were subjected to whole-genome sequencing. Population structure was characterized through phylogenetic analysis, sequence typing, serotyping, virulence factor, and antimicrobial drug resistance (AMR) gene profiling, combining the publicly available related WGS data. Clinical demography and antibiotic susceptibility profiles were compared among different populations to emphasize the higher-risk populations. Genetic regions associated with AMR gene mobilization were identified through comparative genomics. RESULTS: These IPD strains mainly belonged to clonal complex 320 (CC320) and were composed of serotypes 19A and 19F. In addition to sporadic possible importation-related isolates (ST320), we identified an independent clade, CC320_SZpop (ST271), that predominantly circulated in Shenzhen and possibly expanded its range. Clinical features and antibiotic susceptibility analysis revealed that CC320_SZpop might manifest much higher pathogenicity and tolerance to ß-lactams. Specific virulence factors in Shenzhen isolates of CC320_SZpop were identified. Furthermore, an ca. 40 kb hotspot genomic region enduring frequent recombination was identified, possibly associated with the divergence of S. pneumoniae strains. CONCLUSION: A novel pneumococcal clade, CC320_SZpop, circulating in Shenzhen and other regions in China, possibly under expansion, was found and deserves more study and surveillance. Our study also emphasizes the importance of continuous genomic surveillance of clinical S. pneumoniae isolates, especially IPD isolates.

Molecular characteristics and antimicrobial resistance of invasive pneumococcal isolates from children in the post-13-valent pneumococcal conjugate vaccine era in Shenzhen, China.

OBJECTIVES: This study aimed to evaluate the molecular epidemiology and antimicrobial resistance of invasive pneumococcal isolates from children in Shenzhen, China, in the early stage of the pneumococcal 13-valent conjugated vaccine (PCV-13) era from 2018 to 2020. METHODS: Invasive pneumococcal strains were isolated from hospitalized children with invasive pneumococcal diseases (IPDs) from January 2018 to December 2020. The serotype identification, multilocus sequence typing (MLST), and antibiotic susceptibility tests were performed on all culture-confirmed strains. RESULTS: Sixty-four invasive strains were isolated mainly from blood (70.3%). Prevalent serotypes were 23F (28.1%), 14 (18.8%), 19F (15.6%), 6A/B (14.1%), and 19A (12.5%), with a serotype coverage rate of 96.9% for PCV13. The most common sequence types (STs) were ST876 (17.1%), ST271 (10.9%), and ST320 (7.8%). Half of the strains were grouped in clonal complexes (CCs): CC271 (21.9%), CC876 (20.3%), and CC90 (14.1%). Meningitis isolates showed a higher resistance rate (90.9% and 45.5%) to penicillin and ceftriaxone than the rate (3.8% and 9.4%) of non-meningitis isolates. The resistance rates for penicillin (oral), cefuroxime, and erythromycin were 53.13%, 73.4%, and 96.9%, respectively. The dual ermB and mefA genotype was found in 81.3% of erythromycin-resistant strains. The elevated minimum inhibitory concentration (MIC) of ß-lactam antibiotics and dual-genotype macrolide resistance were related mainly to three major serotype-CC combinations: 19F-CC271, 19A-CC271, and 14-CC876. CONCLUSION: Invasive pneumococcus with elevated MICs of ß-lactams and increased dual ermB and mefA genotype macrolide resistance were alarming. Expanded PCV13 vaccination is expected to reduce the burden of paediatric IPD and to combat antibiotic-resistant pneumococcus in Shenzhen.

Transdermal Transfersome Nanogels Control Hypertrophic Scar Formation via Synergy of Macrophage Phenotype-Switching and Anti-Fibrosis Effect.

Hypertrophic scar (HS), which results from prolonged inflammation and excessive fibrosis in re-epithelialized wounds, is one of the most common clinical challenges. Consequently, sophisticated transdermal transfersome nanogels (TA/Fu-TS) are prepared to control HS formation by synergistically inhibiting inflammation and suppressing fibrosis. TA/Fu-TSs have unique structures comprising hydrophobic triamcinolone acetonide (TA) in lipid multilayers and hydrophilic 5-fluorouracil in aqueous cores, and perform satisfactorily with regard to transdermal co-delivery to macrophages and HS fibroblasts in emerging HS tissues. According to the in vitro/vivo results, TA/Fu-TSs not only promote macrophage phenotype-switching to inhibit inflammation by interleukin-related pathways, but also suppress fibrosis to remodel extracellular matrix by collagen-related pathways. Therefore, TA/Fu-TSs overcome prolonged inflammation and excessive fibrosis in emerging HS tissues, and provide an effective therapeutic strategy for controlling HS formation via their synergy of macrophage phenotype-switching and anti-fibrosis effect.

Visualizing ultrafast photothermal dynamics with decoupled optical force nanoscopy.

The photothermal effect in nanomaterials, resulting from resonant optical absorption, finds wide applications in biomedicine, cancer therapy, and microscopy. Despite its prevalence, the photothermal effect in light-absorbing nanoparticles has typically been assessed using bulk measurements, neglecting near-field effects. Beyond standard imaging and therapeutic uses, nanosecond-transient photothermal effects have been harnessed for bacterial inactivation, neural stimulation, drug delivery, and chemical synthesis. While scanning probe microscopy and electron microscopy offer single-particle imaging of photothermal fields, their slow speed limits observations to milliseconds or seconds, preventing nanoscale dynamic investigations. Here, we introduce decoupled optical force nanoscopy (Dofn), enabling nanometer-scale mapping of photothermal forces by exploiting unique phase responses to temporal modulation. We employ the photothermal effect's back-action to distinguish various time frames within a modulation period. This allows us to capture the dynamic photothermal process of a single gold nanorod in the nanosecond range, providing insights into non-stationary thermal diffusion at the nanoscale.

[Risk factors for hemorrhagic cystitis in children with ß-thalassemia major after allogeneic hematopoietic stem cell transplantation]. / 重型ßåœ°ä¸­æµ·è´«è¡€å„¿ç«¥å¼‚åŸºå› é€ è¡€å¹²ç»†èƒžç§»æ¤åŽå¹¶å‘å‡ºè¡€æ€§è†€èƒ±ç‚Žçš„å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To explore the risk factors for hemorrhagic cystitis (HC) in children with ß-thalassemia major (TM) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A retrospective analysis was conducted on clinical data of 247 children with TM who underwent allo-HSCT at Shenzhen Children's Hospital from January 2021 to November 2022. The children were divided into an HC group (91 cases) and a non-HC group (156 cases) based on whether HC occurred after operation. Multivariable logistic regression analysis was used to explore the risk factors for HC, and the receiver operating characteristic curve was used to analyze the predictive efficacy of related factors for HC. RESULTS: Among the 247 TM patients who underwent allo-HSCT, the incidence of HC was 36.8% (91/247). Univariate analysis showed age, incompatible blood types between donors and recipients, occurrence of acute graft-versus-host disease (aGVHD), positive urine BK virus deoxyribonucleic acid (BKV-DNA), and ≥2 viral infections were associated with the development of HC after allo-HSCT (P<0.05). Multivariable analysis revealed that incompatible blood types between donors and recipients (OR=3.171, 95%CI: 1.538-6.539), occurrence of aGVHD (OR=2.581, 95%CI: 1.125-5.918), and positive urine BKV-DNA (OR=21.878, 95%CI: 9.633-49.687) were independent risk factors for HC in children with TM who underwent allo-HSCT. The receiver operating characteristic curve analysis showed that positive urine BKV-DNA alone or in combination with two other risk factors (occurrence of aGVHD, incompatible blood types between donors and recipients) had a certain accuracy in predicting the development of HC after allo-HSCT (area under the curve >0.8, P<0.05). CONCLUSIONS: Incompatible blood types between donors and recipients, occurrence of aGVHD, and positive urine BKV-DNA are risk factors for HC after allo-HSCT in children with TM. Regular monitoring of urine BKV-DNA has a positive significance for early diagnosis and treatment of HC.

Developing an efficient MGCR microneedle nanovaccine patch for eliciting Th 1 cellular response against the SARS-CoV-2 infection.

Rationale: Novel vaccine R&D is essential to interrupt the COVID-19 pandemic and other epidemics in the future. Subunit vaccines have received tremendous attention for their low cost and safety. To improve the immunogenicity of subunit vaccines, we developed a novel vaccine adjuvant system. Methods: Here we rationally designed a CpG 1018 and graphene oxide-based bi-adjuvant system to deliver the Receptor-Binding Domain (RBD) of the SARS-CoV-2 spike protein and obtained the graphene oxide-based complex adjuvant nanovaccine (GCR). Furthermore, we developed a microneedle patch vaccine (MGCR) based on the GCR vaccine. Results: GCR nanovaccine displayed superb antigen loading and encapsulation efficiency. Two dosages of vaccination of GCR nanovaccine could elicit adequate RBD-specific binding antibody response with 2.14-fold higher IgG titer than Alum adjuvant vaccine. The peptide pools assay demonstrated the robust RBD-specific Type 1 Cellular response induced by the GCR nanovaccine in CD8+ T cells. Furthermore, we prepared an MGCR microneedle patch, which generated a similar RBD-specific binding antibody response to the GCR vaccine, sustained a high antibody level above 16 weeks, and significantly elevated the Tcm proportion in mouse spleen. The MGCR microneedle patch vaccine also could be stably stored at room temperature for several months and administrated without medical staff, which maximizes the vaccine distribution efficiency. Conclusion: The vaccine system could significantly improve the vaccine distribution rate in low-income areas and offer a potential vaccination approach to fight against the SARS-Cov-2 infection and other pandemics occurred in the future.

Detecting rare thalassemia in children with anemia using third-generation sequencing.

BACKGROUND: In China, conventional genetic testing methods can only detect common thalassemia variants. Accurate detection of rare thalassemia is crucial for clinical diagnosis, especially for children that need long-term blood transfusion. This study aims to explore the application value of third-generation sequencing (TGS) in the diagnosis of rare thalassemia in children with anemia. METHODS: We enrolled 20 children with anemia, excluding from iron deficiency anemia (IDA). TGS was employed to identify both known and novel thalassemia genotypes, while sanger sequencing was used to confirm the novel mutation detected. RESULTS: Among the 20 samples, we identified 5 cases of rare thalassemia. These included ß-4.9 (hg38,Chr11:5226187-5231089) at HBB gene, α-91(HBA2:c.*91delT), αCD30(HBA2:c.91-93delGAG), Chinese Gγ+(Aγδß)0(NG_000007.3: g .48795-127698 del 78904) and delta - 77(T > C)(HBD:c.-127T>C). Notably, the -SEA/α-91α genotype associated with severe non-deletional hemoglobin H disease (HbH disease) has not been previously reported. Patients with genotypes ß654/ß-4.9 and -SEA/α-91α necessitate long-term blood transfusions, and those with the -SEA/αCD30α, Chinese Gγ+(Aγδß)0 and delta thalassemia demonstrate mild anemia. CONCLUSIONS: TGS demonstrates promising potential as a diagnostic tool for suspected cases of rare thalassemia in children, especially those suspected to have transfusion-dependent thalassemia (TDT).

Trends in Antibiotic Resistance Patterns and Burden of Escherichia Coli Infections in Young Children: A Retrospective Cross-Sectional Study in Shenzhen, China from 2014-2018.

Purpose: The emergence of multi-drug resistant ESBL-producing E. coli poses a global health problem. In this study, we aimed to investigate the prevalence of E. coli infections and their antibiotic susceptibility profiles in paediatric clinical cases in Shenzhen, China from Jan 1, 2014, to Jan 30, 2019, while also determining temporal trends, identifying ESBL-producing strains, and recommending potential empirical antibiotic therapy options. Methods: We isolated a total of 4148 E. coli from different specimens from a single paediatric healthcare centre. Additionally, we obtained relevant demographic data from the hospital's electronic health records. Subsequently, we performed antimicrobial susceptibility testing for 8 classes of antibiotics and assessed ESBL production. Results: Out of the 4148 isolates, 2645 were from males. The highest burden of E. coli was observed in the age group of 0-1 years, which gradually declined over the five-year study period. Antimicrobial susceptibility results indicated that 82% of E. coli isolates were highly resistant to ampicillin, followed by 52.36% resistant to cefazolin and 47.46% resistant to trimethoprim/sulfamethoxazole. Notably, a high prevalence of ESBL production (49.54%) was observed among the E. coli isolates, with 60% of them displaying a multi-drug resistance phenotype. However, it is worth mentioning that a majority of the isolates remained susceptible to ertapenem and imipenem. Our findings also highlighted a decrease in E. coli infections in Shenzhen, primarily among hospitalized patients in the 0-1 year age group. However, this decline was accompanied by a considerably high rate of ESBL production and increasing resistance to multiple antibiotics. Conclusion: Our study underscores the urgent need for effective strategies to combat multi-drug resistant ESBL-producing E. coli Infections.

Hyaluronic acid-modified and verteporfin-loaded polylactic acid nanogels promote scarless wound healing by accelerating wound re-epithelialization and controlling scar formation.

Wound healing is a common occurrence. However, delayed healing and aberrant scarring result in pathological wound healing. Accordingly, a scarless wound healing remains a significant clinical challenge. In this study, we constructed hyaluronic acid (HA)-modified and verteporfin (VP)-loaded polylactic acid (PLA) nanogels (HA/VP-PLA) to promote scarless wound healing by accelerating wound re-epithelialization and controlling scar formation. Owing to the unique structure of HA incorporating and coating in VP-loaded PLA nanoparticles, HA/VP-PLA could be topically applied on wound to achieve targeted delivery to fibroblasts. Then, HA/VP-PLA released HA and lactic acid (LA) to stimulate the proliferation and migration of fibroblasts, as well as VP to inhibit Yes-associated protein (YAP) expression and nuclear localization to suppress fibrosis. In vitro (skin fibroblasts) and in vivo (rat and rabbit models) experiments strongly suggested that HA/VP-PLA promoted scarless wound healing by accelerating wound re-epithelialization and controlling scar formation. Therefore, our work provides a feasible strategy for scarless wound healing, and the sophisticated HA/VP-PLA exhibit a great potential for clinical applications.

Genomic characterisation of multi-drug resistant Escherichia coli and Klebsiella pneumoniae co-harbouring mcr-1 and mcr-3 genes on a single plasmid from paediatric clinical cases.

OBJECTIVES: Emergence of the plasmid-born mobile colistin resistance (mcr) gene is a growing concern in healthcare. Therefore, this study aimed to genomically characterise multidrug-resistant Escherichia coli and Klebsiella pneumoniae co-harbouring the mcr-1 and mcr-3 genes in young children. METHODS: E. coli (n = 3) and K. pneumoniae (n = 2) were collected from abdominal secretions and blood, respectively. The isolates were screened using tryptone soy broth with 4 µL/mL polymyxin-B. Growing bacteria were identified using the VITEK-2 system, matrix-assisted laser desorption/ionisation time-of-flight, and 16s RNA sequencing, followed by antibiotic susceptibility testing. Metallo-ß-lactamase (MBL) and extended-spectrum ß-lactamase (ESBL) production was also detected. Afterwards, strains were subjected to molecular screening targeting mcr variants and ESBL/MBL-encoding genes. Conjugation, pulsed-field gel electrophoresis, Southern hybridisation, multilocus sequence typing, and phylogenic group detection were performed, along with plasmid-genome sequencing and bioinformatics analysis. RESULTS: E. coli isolates (EC-19-322, 323, and 331) and K. pneumoniae isolates (KP-19-225 and 226) harboured both mcr-1 and mcr-3 genes. These strains were also found to be resistant to more than three classes of antibiotics. The conjugation experiment revealed the presence of mcr-1 and mcr-3 on a single plasmid, and the transmission frequency was 10-2 to 10-3. Both strains were found to be able to produce ESBLs and MBL. E. coli EC-19-322 and 323 were identified as ST131(O25a:H41); SP-19-331, as ST1577 (O16:H30); and K. pneumoniae, as ST231 (K2). All E. coli strains belonged to phylogenetic group B2, and the results of pulsed-field gel electrophoresis supported the multilocus sequence typing findings. CONCLUSION: This study reported the co-occurrence of mcr-1 and mcr-3 genes on a single plasmid in pathogenic ESBL/MBL-producing E. coli and K. pneumoniae isolated from young children.

Observing the Clinical Outcomes of Single Port Endoscopic Posterolateral TLIF in Retired Athletes

Objective To investigate the clinical outcomes of single port endoscopic posterolateral transforaminal lumbar interbody fusion (TLIF) in athletic patients. Methods Retrospective analysis was done on the clinical information of 82 athletic patients suffering from degenerative scoliosis who were operated at our hospital's spine surgery department from April 2020 to December 2021. They were split into an observing and a controlling group using the random number table approach, with 41 cases per group. The controlling group had open TLIF therapy, whereas the observing group received single-hole endoscopic TLIF. Both groups' operational indicators were scrutinized. We contrasted the preoperative and postoperative results of both groups for the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), Japanese Orthopedic Association score (JOA), Cobb angle, lumbar lordosis angle, sacral inclination angle, and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Both groups' postoperative bone graft fusion was seen. Results Athletic Patients in the observing group underwent operations with considerably less time and blood loss versus to those in the controlling group (P <0.05). In terms of surgical drainage volume and hospital stay, there was no clinically meaningful variation among both groups (P > 0.05). The VAS and ODI scores of both groups were substantially lower after surgery than before, whereas the JOA score was substantially greater (P <0.05). After the procedure, the observing group's VAS and ODI scores were substantially lower versus to those of the controlling group, although their JOA scores were substantially higher (P <0.05). (AU)

Bacillus pfraonensis sp. nov., a new strain isolated from a probiotic feed additive with low cytotoxicity and antimicrobial activity.

Probiotic products containing living microorganisms are gaining popularity, increasing the importance of their taxonomic status. A Bacillus-like isolate, 70 b, cultured from a probiotic feed additive, was ambiguity in taxonomic assignment and could be a novel member of Bacillus cereus group. The results of colony and cellular morphology, physiological and biochemical analysis mainly including growth performance, carbon source utilization, and rMLST and MLST were not conclusive. Fatty acids profile and molecular genetic analysis especially ANI, DDH, and core genome SNPs-based phylogenetic tree confirmed 70 b as one novel species of B. cereus group and proposed as Bacillus pfraonensis sp. nov. Comparative genomic analysis revealed the genetic differences between 70 b and other species of B. cereus group. Pseudomycoicidin was identified in 70 b. 70 b was active against multidrug-resistant pathogenic strains MRSA. The findings support 70 b is a novel species with low cytotoxicity and antimicrobial activity, and provides a better understanding of its unique characteristics and probiotic potential, and exploration of bioactive potential.

Characterization of resistance genes and plasmids from sick children caused by Salmonella enterica resistance to azithromycin in Shenzhen, China.

Introduction: Samonella is 1 of 4 key global causes of diarrhoeal diseases, sometimes it can be serious, especially for yong children. Due to the extensive resistance of salmonella serotypes to conventional first-line drugs, macrolides (such as azithromycin) have been designated as the most important antibiotics for the treatment of salmonella. Antimicrobial resistance is a major public health problem in the world, and the mechanism of azithromycin resistance is rarely studied. Methods: This study determined the azithromycin resistance and plasmids of Salmonella enterica isolates from children attending the Shenzhen Children's Hospital. The susceptibility of ampicillin (AMP), ciprofloxacin (CIP), ceftriaxone (CRO), sulfamethoxazole (SMZ), chloramphenicol (CL), and azithromycin (AZM) were detected and the genes and plasmids from azithromycin-resistant Salmonella were detected by Illumina hi-seq and Nanopore MinIone whole genome sequencing (WGS) using a map-based method, and the genomic background of these factors was evaluated using various bioinformatics tools. Results: In total, 15 strains of nontyphoid Salmonella strains that were isolated (including S. typhimurium, S.London, S. Goldcoast, and S.Stanley) demonstrated resistance to azithromycin (minimum inhibitory concentration,MIC from 32 to >256 µg/mL), and the resistance rate was 3.08% (15/487). The sensitivity test to other antibiotics demonstrated 100% resistance to AMP, and the resistance to SMZ and CL was 86.7% and 80.0%, respectively. Through WGS analysis, all isolates were positive for a plasmid-encoded mphA gene. Plasmid incompatibility typing identified five IncFIB(K), five IncHI2/HI2A/Q1, two IncC, one IncHI2/HI2A/N, one IncR, one IncFII and one IncHI2/HI2A plasmids. Sequence analyses of plasmids revealed extensive homology to various plasmids or transposons in regions involved in plasmid replication/maintenance functions and/or in antibiotic resistance gene clusters. Conclusion: mphA is the main gene involved in azithromycin, a macrolide, and resistance to Salmonella. It is usually located on plasmids and easily spreads, hence posing a great threat to the current treatment of Salmonella infection. The plasmid sequence similarities suggest that the plasmids acquired resistance genes from a variety of enterica bacteria and underscore the importance of a further understanding of horizontal gene transfer among enterica bacteria.