Can rifaximin for hepatic encephalopathy be discontinued during broad-spectrum antibiotic treatment?

Hepatic encephalopathy(HE)is a formidable complication in patients with decompensated cirrhosis,often necessitating the administration of rifaximin(RFX)for effective management.RFX,is a gut-restricted,poorly-absorbable oral rifamycin derived antibiotic that can be used in addition to lactulose for the secondary prophylaxis of HE.It has shown notable reductions in infection,hospital readmission,duration of hospital stay,and mortality.However,limited data exist about the concurrent use of RFX with broad-spectrum antibiotics,because the patients are typically excluded from studies assessing RFX efficacy in HE.A pharmacist-driven quasi-experimental pilot study was done to address this gap.They argue against the necessity of RFX in HE during broad-spectrum antibiotic treatment,particularly in critically ill patients in intensive care unit(ICU).The potential for safe RFX discontinuation without adverse effects is clearly illuminated and valuable insight into the optimization of therapeutic strategies is offered.The findings also indicate that RFX discontinuation during broadspectrum antibiotic therapy was not associated with higher rates of delirium or coma,and this result remained robust after adjustment in multivariate analysis.Furthermore,rates of other secondary clinical and safety outcomes,including ICU mortality and 48-hour changes in vasopressor requirements,were comparable.However,since the activity of RFX is mainly confined to the modulation of gut microbiota,its potential utility in patients undergoing extensive systemic antibiotic therapy is debatable,given the overlapping antibiotic activity.Further,this suggests that the action of RFX on HE is class-specific(related to its activity on gut microbiota),rather than drug-specific.A recent double-blind randomized controlled(ARiE)trial provided further evidence-based support for RFX withdrawal in critically ill cirrhotic ICU patients receiving broad-spectrum antibiotics.Both studies prompt further discussion about optimal therapeutic strategy for patients facing the dual challenge of HE and systemic infections.Despite these compelling results,both studies have limitations.A prospective,multi-center evaluation of a larger sample,with placebo control,and comprehensive neurologic evaluation of HE is warranted.It should include an exploration of longer-term outcome and the impact of this protocol in non-critically ill liver disease patients.

Screening of Broad-spectrum Resistance Resources against Rice Bacterial Leaf Streak

[ Objectives] Rice materials with broad-spectrum resistance against several pathogenic strains of Xanthomans oryzae pv. Oryzicola （Xooc） at multiple growth stages were screened, in order to provide reliable resistance sources for variety breeding against rice bacterial leaf streak. [ Methods] A total of 1 100 rice lines with rich genetic background were offered as selective objects, and highly susceptible cultivar Jingang 30 was used as the control. Inoculation was carried out with five strong pathogenic strains of Xooc through acupuncture method at various growth stages for resistance identification. [ Results] Fourteen disease-resistant materials were obtained through preliminary screening, accounting for 1.27% of the total materials. Nine materials moderately resistant to bacterial leaf streak were obtained via secondary screening, accounting for 0.82% of the total materials. Besides, three of them （ RL6, RL9 and RLL4） were resistant to a number of pathogenic strains of Xooc at three growth stages. In particular, RL16 presented broad-spectrum resistance to multi-strains with high resistance levels. Six of them （ RI2, RIA, RIS, RL8, RL11 and RL12） were resistant to single strain at single growth stage. [ Conclusions] The obtained three materials have broad-spectrum resistance to bacterial leaf streak at multiple growth stages, which can be served as an important source to cultivate disease-resistant rice varieties. RL6 maintains high broad-spectrum resistance at all growth stages, which can be used as a prior resistance source for rice variety breeding. Six materials obtained with resistance against bacterial leaf streak at particular growth stages can be used as candidate resistance sources.

Traditional Chinese medicine:an important broad-spectrum anti-coronavirus treatment strategy on COVID-19 background?

Coronaviruses exist widely in nature,can cause cross-species transmission,and pose serious threats to human and animal health.Over the past 20 years,coronaviruses have led to three major epidemics that have caused global panic,including severe acute respiratory syndrome,Middle East respiratory syndrome,and coronavirus disease-19.At present,coronavirus disease 19 not only spreads rapidly,but also mutates easily to escape host immune response,becoming more pathogenic.At present,there are no effective specific therapeutic drugs or vaccines.Drugs targeting severe acute respiratory syndrome coronavirus 2 and the host cell defense system that have been developed based on the structure and replication cycle of coronaviruses have a certain broad-spectrum antiviral effect;however,their efficacy still needs to be demonstrated in further clinical trials.Traditional Chinese medicine has an indispensable role in the ongoing response to coronavirus disease-19.Anti-virus treatment with traditional Chinese medicine has advantages such as broad-spectrum application,low toxicity and side effects,low susceptibility to drug resistance,and overall comprehensive regulation.Therefore,researches on effective components and mechanisms of action of the anti-viral effects of traditional Chinese medicine have increasingly gained attention.The present paper examines coronaviruses,specifically summarizing the genomes,replication mechanisms,and mutant strains.Afterward,the therapeutic effects and mechanisms of action of modern broad-spectrum anti-coronavirus drugs and traditional Chinese medicine are summarized.By considering the virus and the targets in the host comprehensively,in addition to the beneficial multi-target and multi-path antiviral effects of traditional Chinese medicines,this paper could guide the development of treatment strategies for broad-spectrum anti-coronavirus traditional Chinese medicines,and could facilitate the modernization and globalization of traditional Chinese medicine.

Increasing Incidence of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae (ESBL) and the Relation to Consumption of Broad-Spectrum Antimicrobial Agents 2003-2011 in a Large Area of Copenhagen, Denmark

Purpose: To investigate 1) the development in the incidence of ESBL-producing bacteria in hospitals and primary health care, 2) the contribution of primary health care to the incidence of ESBL-producing bacteria, and 3) the development in resistance patterns for all Escherichia coli and Klebsiella pneumoniae isolates in relation to antimicrobial consumption in hospitals and primary health care. Methods: ESBL-data were retrospectively collected from bacterial isolates from all specimens received at the Department of Clinical Microbiology from 2003 to 2011 together with the corresponding patient data. ESBL-production was detected in isolates from 1067 of 59,373 patients (1.8%) with an E. coli infection and in 263 of 8660 patients (3.0%) with a K. pneumoniae infection. Results: From 2003 to 2009, an increase in patients with an ESBL-producing isolate occurred in both hospitals and primary health care at the same time as an increased consumption of broad-spectrum antimicrobial agents was seen. Interventions to reduce prescription of cephalosporins and ciprofloxacin at the hospitals from 2010 resulted in a remarkable decrease in patients with ESBL-producing K. pneumoniae whereas a continuing increase was seen in patients with ESBL-producing E. coli both at hospitals and in primary health care. The proportion of patients with community-acquired ESBL-producing E. coli was stable with an increase of only 1.4% from 2007 to 2011. Conclusions: Reduction in prescription of broad-spectrum antimicrobial agents at the hospital level had an important impact on the incidence of ESBL-producing K. pneumoniae, but not on ESBL-producing E. coli.

Research Progress in Molecular Mechanism of Broad-spectrum Disease Resistance in Rice

Yield loss caused by crop diseases seriously restricts global food security.Breeding disease-resistant varieties with resistance(R)genes is acknowledged as the most economical and effective way to control diseases.Therefore,exploring broad-spectrum resistance(BSR)genes to pathogens and clarifying the underlying mechanism are the basis for effective utilization of BSR resources and finding new approaches for disease control.In the past 20 years,significant progress has also been made in plant immune mechanism and remarkable achievements have been made in researches on broad-spectrum disease resistance of major grain crops,and the potential molecular mechanisms of some BSR have been revealed.Here,the advances of broad-spectrum disease resistance in rice(including the representative cloned BSR genes and their molecular mechanisms)were reviewed.In addition,the problems,opportunities and challenges encountered by BSR were analyzed,and the development of BSR research and its application in rice production were prospected.

Effectiveness of a Broad-Spectrum Sunscreen in the Prevention of Melasma in Asian Pregnant Women

Chloasma, or melasma, is a commonly acquired pigmentary disorder among Asian women. It may be considered as a physiological change during pregnancy. The incidence in Asian women is higher than that in other ethnic groups but further epidemiologic data are needed. There are very few studies related to the benefits of sunscreens to prevent this dermatosis. The aim of this study was to assess the effectiveness of a broad-spectrum sunscreen in the prevention of melasma in Korean pregnant women. We tested the effectiveness and tolerance of a sunscreen product (SPF 50+, UVA-PF 30) during a 12-month clinical trial including 220 Korean parturients with skin type III and IV. 217 women completed the study. Only 3 (1%) of the study population developed melasma, which was mild (MASI grade between 1.2 and 2.7). In addition, the clinical effectiveness of the evaluated sunscreen was judged “good to excellent” by the majority of study participants and by the research dermatologists. The “excellent” tolerance of the sunscreen under evaluation was confirmed “good” to “excellent” in 95% and 97% of cases. This study clearly demonstrates that this broad-spectrum sunscreen is well tolerated and effective in the prevention of melasma in Korean pregnant women. Although treatment remains elusive, prevention is possible.

Analysis of Enterobacteriaceae Producing Broad-Spectrum Beta-Lactamases in the Intensive Care Unit Setting

Strains of the Enterobacteriaceae family producing ESBL and AmpC broad-spectrum beta-lactamases that may survive in the hospital setting potentially cause infection in hospitalized patients due to contaminated objects or health care workers’ hands. Over a period of two months (November-December 2010), a single epidemiological study of microbial contamination of air, surfaces and health care workers (swabs from both nostrils and the right hand without a glove) was carried out at two intensive care units of the University Hospital Olomouc, Czech Republic. The bacteria were identified using standard microbiological methods. Phenotypic detection of ESBL and AmpC enzymes and basic genetic analysis of ESBL- and AmpC-positive isolates was performed. The same approach was used to identify and analyze bacteria isolated from clinical samples of patients hospitalized at the above departments over the study period. From a total of 140 environmental samples collected over the study period, 21 isolates of the Enterobacteriaceae family were identified, with ESBL and AmpC production being detected in 4 and 7 isolates, respectively. Among patients’ clinical samples, 10 ESBL- and 6 AmpC-positive isolates were detected. No similarity was found between environmental isolates and strains isolated from patients.

Co-production of Multiple Antimicrobial Compounds by Bacillus amyloliquefaciens WY047,a Strain with Broad-Spectrum Activity

A bacterial strain WY047 was isolated from fermented grains and the bacterium was identified as Bacillus amyloliquefaciens, based on morphological, biochemical, and physiological tests, and analysis of 16S rRNA and gyr A sequences. The culture supernatant of WY047 demonstrated inhibition ofa wide spectrum ofbacteria(Gram positive and Gram negative) and fungi. Nine pairs ofprimers were designed and six genes( bmyD, fenA, hag, ituA, mrsA, and tasA) ofantimicrobial substances were detected by PCR, one ofwhich was isolated by 80% ammonium sulfate precipitation, D201 resin anion-exchange chromatography, and Sephadex G-75 filtration column. The purified peptide was estimated to be 35,207 Da and identified as flagellin by MALDI-TOF mass spectrometry. Another four antimicrobial substances were extracted with methanol and identified as iturin A, fengycin, bacillomycin D, and mersacidin through the liquid chromatography–mass spectrometry(LC–MS) method. The sixth possible peptide encoded by tas A could not be isolated in this study; however, the broader spectrum suggested huge application prospects.

Improving treatment plan and mental health in children with abdominal infection for broad-spectrum bacterial infections

BACKGROUND Pediatric abdominal infection is a common but serious disease that requires timely and effective treatment.In surgical treatment,accurate diagnosis and rational application of antibiotics are the keys to improving treatment effects.AIM To investigate the effect of broad-spectrum bacterial detection on postoperative antibiotic therapy.METHODS A total of 100 children with abdominal infection who received surgical treatment in our hospital from September 2020 to July 2021 were grouped.The observation group collected blood samples upon admission and sent them for broad-spectrum bacterial infection nucleic acid testing,and collected pus or exudate during the operation for bacterial culture and drug sensitivity testing;the control group only sent bacterial culture and drug sensitivity testing during the operation.RESULTS White blood cell count,C-reactive protein,procalcitonin,3 days after surgery,showed better postoperative index than the control group(P<0.05).The hospital stay in the observation group was significantly shorter than that in the control group.The hospitalization cost in the observation group was significantly lower than that in the control group,and the difference between the two groups was statistically significant(P<0.05).CONCLUSION Early detection of broad-spectrum bacterial infection nucleic acids in pediatric abdominal infections can help identify pathogens sooner and guide the appropriate use of antibiotics,improving treatment outcomes and reducing medical costs to some extent.

The host-targeting compound peruvoside has a broad-spectrum antiviral activity against positive-sense RNA viruses

Positive-sense RNA viruses modify intracellular calcium stores,endoplasmic reticulum and Golgi apparatus(Golgi)to generate membranous replication organelles known as viral factories.Viral factories provide a conducive and substantial enclave for essential virus replication via concentrating necessary cellular factors and viral proteins in proximity.Here,we identified the vital role of a broadspectrum antiviral,peruvoside in limiting the formation of viral factories.Mechanistically,we revealed the pleiotropic cellular effect of Src and PLC kinase signaling via cyclin-dependent kinase 1 signaling leads to Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1(GBF1)phosphorylation and Golgi vesiculation by peruvoside treatment.The ramification of GBF1 phosphorylation fosters GBF1 deprivation consequentially activating downstream antiviral signaling by dampening viral factories formation.Further investigation showed signaling of ERK1/2 pathway via cyclin-dependent kinase 1 activation leading to GBF1 phosphorylation at Threonine 1337(T1337).We also showed 100%of protection in peruvoside-treated mouse model with a significant reduction in viral titre and without measurable cytotoxicity in serum.These findings highlight the importance of dissecting the broad-spectrum antiviral therapeutics mechanism and pave the way for consideration of peruvoside,host-directed antivirals for positive-sense RNA virus-mediated disease,in the interim where no vaccine is available.

Membrane-targeting amphiphilic AIE photosensitizer for broad-spectrum bacteria imaging and photodynamic killing of bacteria

An amphiphilic AIE photosensitizer has been successfully developed,which allows for easily inserting into the bacterial membranes.Binding experiments with phospholipid preliminary demonstrates its membrane specificity.As expected,it is proved to possess a broad-spectrum bacterial staining performance and photodynamic antibacterial activity toward S.aureus and E.coli.

Pijx confers broad-spectrum seedling and panicle blast resistance by promoting the degradation of ATP β subunit and OsRbohC-mediated ROS burst in rice

Rice blast,caused by the fungal pathogen Magnaporthe oryzae,is one of the most important diseases of rice.Utilization of blast-resistance genes is the most economical,effective,and environmentally friendly way to control the disease.However,genetic resources with broad-spectrum resistance(BSR)that is effective throughout the rice growth period are rare.In this work,using a genome-wide association study,we identify a new blast-resistance gene,Pijx,which encodes a typical CC-NBS-LRR protein.Pijx is derived from a wild rice species and confers BSR to M.oryzae at both the seedling and panicle stages.The functions of the resistant haplotypes of Pijx are confirmed by gene knockout and overexpression experiments.Mechanistically,the LRR domain in Pijx interacts with and promotes the degradation of the ATP synthase β subunit(ATPb)via the 26S proteasome pathway.ATPb acts as a negative regulator of Pijx-mediated panicle blast resistance,and interacts with OsRbohC to promote its degradation.Consistently,loss of ATPb function causes an increase in NAPDH content and ROS burst.Remarkably,when Pijx is introgressed into two japonica rice varieties,the introgression lines show BSR and increased yields that are approximately 51.59%and 79.31%higher compared with those of their parents in a natural blast disease nursery.In addition,we generate PPL^(Pijx Pigm) and PPL^(Pijx Piz-t) pyramided lines and these lines also have higher BSR to panicle blast compared with Pigm-or Piz-t-containing rice plants.Collectively,this study demonstrates that Pijx not only confers BSR to M.oryzae but also maintains high and stable rice yield,providing new genetic resources and molecular targets for breeding rice varieties with broad-spectrum blast resistance.

Rational hapten design and establishment of broad-spectrum indirect competitive enzyme-linked immunosorbent assay for benzimidazoles monitoring in milk

Objectives Benzimidazoles(BZs)are commonly used for the treatment of soil-transmitted helminth infections in veterinary clinics;however,misuse and overdosing of BZs will cause residual problems and have the potential to damage human health through the food chain.Thus,the existence of BZs in foods needs more attention.This study aims to establish a broad-spectrum immunoassay for rapid detection and to simultaneously monitor BZs in milk.Materials and Methods Based on structure analysis,a‘zero epitope loss’strategy,which introduced a spacer arm into the imino group of the imidazole ring of albendazole,was first adopted for hapten modification to obtain an ultra-sensitive and broad-spectrum antibody.An indirect competitive enzyme-linked immunosorbent assay(icELISA)was established for the detection of 18 BZs in milk sample with a single-step pretreatment.A quantitative structure–activity relationship model was constructed to interpret and predict the recognition.Results The antibody could recognize 20 BZs and the half-inhibitory concentrations ranged from 0.054 to 417.58 ng/mL,the limits of detection of icELISA ranged from 0.4 to 89.4 ng/mL,and the mean recovery rates ranged from 76.49%to 120.40%,with a coefficient of variation<20%.Substituent R1 of BZs was considered to be the main influencing factor for recognition,and the comparative molecular field analysis model(q2=0.724,r2=0.998)was finally chosen for further prediction.Conclusions The results indicated that the established icELISA could simultaneously identify 18 BZs,with good accuracy and precision,which was suitable for rapid detection of BZs in milk.

传统发酵乳品中产广谱细菌素乳酸菌选育

为选育产广谱细菌素乳酸菌,采用琼脂扩散法对甘肃牧区传统发酵乳品中分离纯化的96株乳酸菌进行了筛选,并确定产细菌素菌株,具有最佳抑菌效果的菌株经重离子束12C6+辐照诱变,再采用培养皿分区法进行6种指示菌广谱抑菌性能比较。结果表明,琼脂扩散法筛选出抑菌效果最佳的产细菌素菌株Lp1,经辐照诱变得到98株突变菌,选育出对大肠埃希氏菌(Escherichia coli)、金黄色葡萄球菌(Staphylococcus aureus)、单核细胞增生李斯特氏菌(Listeria monocytogenes)、沙门氏菌(Salmonella)、志贺氏菌(Shigella)和克罗诺杆菌(Cronobacter)抑菌性能均明显优于出发菌株Lp1的5株突变株L088、L087、L063、L049、L010进行广谱抑菌试验,其中菌株L088和L063为广谱抑菌性能较好菌株,突变株L088对上述6种指示菌的抑菌扇环半径比出发菌株Lp1抑菌扇环半径分别提高47.81%、33.28%、22.97%、45.25%、21.39%、40.21%,突变株L063对上述6种指示菌的抑菌扇环半径比出发菌株Lp1抑菌扇环半径分别提高54.27%、29.18%、25.37%、58.03%、17.85%、42.13%。采用培养皿分区法可同时在1个培养皿中完成检测6种指示菌的抑菌试验,可高效筛选产广谱细菌素乳酸菌。

OsWRKY65 enhances immunity against fungal and bacterial pathogens in rice

Diverse bacterial and fungal pathogens attack plants,causing biotic stress and severe yield losses globally.These losses are expected to become more serious as climate change improves conditions for many pathogens.Therefore,identifying genes conferring broad-spectrum disease resistance and elucidating their underlying mechanisms provides important resources for plant breeding.WRKY transcription factors affect plant growth and stress responses.However,the functions of many WRKY proteins remain to be elucidated.Here,we demonstrated the role of rice(Oryza sativa)WRKY groupⅢtranscription factor OsWRKY65 in immunity.OsWRKY65 localized to the nucleus and acted as transcriptional repressor.Genetic and molecular functional analyses showed that OsWRKY65 increases resistance to the fungal pathogen Fusarium fujikuroi through downregulation of GA signaling and upregulation of JA signaling.Moreover,OsWRKY65 modulated the expression of the key genes that confer susceptibility or resistance to Xanthomonas oryzae pv.oryzae to enhance immunity against the pathogen.In particular,OsWRKY65directly bound to the promoter region of OsSWEET13 and repressed its expression.Taken together,our findings demonstrate that the OsWRKY65 enhances resistance to fungal and bacterial pathogens in rice.

Visible-to-near-infrared photodetectors based on SnS/SnSe_(2)and SnSe/SnSe_(2)p−n heterostructures with a fast response speed and high normalized detectivity

The emergent two-dimensional(2D)material,tin diselenide(SnSe_(2)),has garnered significant consideration for its potential in image capturing systems,optical communication,and optoelectronic memory.Nevertheless,SnSe_(2)-based photodetection faces obstacles,including slow response speed and low normalized detectivity.In this work,photodetectors based on SnS/SnSe_(2)and SnSe/SnSe_(2)p−n heterostructures have been implemented through a polydimethylsiloxane(PDMS)−assisted transfer method.These photodetectors demonstrate broad-spectrum photoresponse within the 405 to 850 nm wavelength range.The photodetector based on the SnS/SnSe_(2)heterostructure exhibits a significant responsivity of 4.99×10^(3)A∙W^(−1),normalized detectivity of 5.80×10^(12)cm∙Hz^(1/2)∙W^(−1),and fast response time of 3.13 ms,respectively,owing to the built-in electric field.Meanwhile,the highest values of responsivity,normalized detectivity,and response time for the photodetector based on the SnSe/SnSe_(2)heterostructure are 5.91×10^(3)A∙W^(−1),7.03×10^(12)cm∙Hz^(1/2)∙W−1,and 4.74 ms,respectively.And their photodetection performances transcend those of photodetectors based on individual SnSe_(2),SnS,SnSe,and other commonly used 2D materials.Our work has demonstrated an effective strategy to improve the performance of SnSe_(2)-based photodetectors and paves the way for their future commercialization.

高性能YVO_(4)基稀土杂化发光材料的构建及其能量传递机制

采用溶剂热和离子交换两步实验法,以YVO_(4)为无机基质,2-噻吩甲酰三氟丙酮(TTA)为有机配体,构建了具有核壳结构的YVO_(4)∶Eu^(3+)@YVO_(4)∶Eu^(3+)-TTA稀土杂化发光材料,研究了其高效的发光性能和内部的能量传递机制。结果表明,在621nm的监控波长下,YVO_(4)∶Eu^(3+)@YVO_(4)∶Eu^(3+)-TTA稀土杂化发光材料在280~420nm范围内有两个很强的吸收峰(即V-O峰和TTA特征吸收峰)。YVO_(4)基质通过交换作用能量传递,而TTA有机配体通过分子内能量传递,可将吸收的紫外光能量有效地传递给Eu^(3+),从而实现了Eu^(3+)更高效的可见光(红光)发射。

Natural Products and Antiviral Resistance

Viral diseases are minacious with the potential for causing pandemics and treatment is complicated because of their inherent ability to mutate and become resistant to drugs. Antiviral drug resistance is a persistent problem that needs continuous attention by scientists, medical professionals, and government agencies. To solve the problem, an in-depth understanding of the intricate interplay between causes of antiviral drug resistance and potential new drugs specifically natural products is imperative in the interest and safety of public health. This review delves into natural product as reservoir for antiviral agents with the peculiar potentials for addressing the complexities associated with multi-drug resistant and emerging viral strains. An evaluation of the mechanisms underlying antiviral drug activity, antiviral drug resistance is addressed, with emphasis on production of broad-spectrum antiviral agents from natural sources. There is a need for continued natural product-based research, identification of new species and novel compounds.

Portraying Diabetic Foot Ulcers: Comparative Evaluation of Diabetic Foot Infections versus Diabetic Foot Ulcers

Background: Confusion often arises in caring for diabetic foot infections and ulcers, especially with antimicrobials;we aim to shed light on this entity and alert healthcare workers to its stewardship. Methods: Records were reviewed between February 2016 and September 2023. Data for patients diagnosed with diabetes and foot ulcers, infected or not, were examined following ICD 9 search terms. Records for patients were included if they were prediabetic/diabetic adults with foot ulcers, more than 18 years old, and on antidiabetic treatment. Patients were excluded if they insulin resistant, with normal HgbA1c levels, wheel-chair dependent, bed-bound, non-diabetic patients, diabetic patients who had vascular lower limb surgery earlier to ulcers, diabetic patients who had aortocoronary bypass, deep venous thrombosis within six months, malignancy, and severe clinical depression. A modified IWGDF/IDSA guidelines definitions for DFI and DFU was considered. Statistical analysis was done using R programming. Statistical methods were employed as appropriate, and a significant P-value was considered for P Results: Most characteristics were well balanced between DFI and DFU, on imaging osteomyelitis and tissue swelling were significantly more in DFI. Endovascular radiological procedures showed angiograms to be considerably more in DFI, while angioplasty was more in DFU, in addition to smoking. Bacteremia was uncommon, and swab cultures were mostly polymicrobial in both ulcers;no clear association with blood bacteria was detected with the polymicrobial growth, though few were concordant. Antimicrobials prescribed for both ulcers were not statistically different except for carbapenems, which were more in DFI (P Conclusion: Attention should be paid to best practices while caring for diabetic ulcers. These include swab culture interpretations, the use of antimicrobials, and plan management according to DFI or DFU to utilize either local care or combination with antimicrobials.

合成生物学在新冠病毒广谱疫苗研发中的应用

新型冠状病毒(SARS-CoV-2)自2019年底引发疫情至今,已经变异出Alpha、Beta、Delta和Omicron等不同谱系。传统疫苗的抗原序列来源于某一自然分离株的原始序列,疫苗迭代速度跟不上病毒变异的速度,导致突破性感染的发生,研发跨谱系的广谱疫苗是预防这类高变异呼吸道病毒的迫切需求。随着合成生物技术的发展,抗原的多价偶联、核心抗原模块的提取、抗原内部保守表位的工程化设计、抗原表位展示技术、计算指导的抗原重构等抗原“再设计”方案得以实现,提高了抗原的免疫原性和广谱性。合成生物学还体现在疫苗产品的生产工艺环节,基因工程表达的疫苗抗原以纳米颗粒、病毒载体、核酸、亚单位的形式,借助细菌、酵母、植物、昆虫或哺乳动物细胞等表达平台进行规模化生产。本文综述了近年来合成生物技术在广谱疫苗(尤其是广谱新冠病毒疫苗)多种设计策略中的应用情况,总结了合成生物技术如何通过反向疫苗学的设计展示全新的共性抗原表位和交叉抗原位点,达到“以不变应万变”的广谱保护效果。本文还讨论了多种广谱疫苗设计策略的应用场景及面临的挑战。基于合成生物技术的马赛克设计策略、保守表位工程化设计策略、计算共识序列策略和新型佐剂策略,结合不同的疫苗技术路线,可提高疫苗的免疫原性、广谱保护性和安全性。这为高变异病毒的疫苗研发提供了合成生物学的新思路。