The metabolic slowdown caused by the deletion of pspA accelerates protein aggregation during stationary phase facilitating antibiotic persistence.

Entering a dormant state is a prevailing mechanism used by bacterial cells to transiently evade antibiotic attacks and become persisters. The dynamic progression of bacterial dormancy depths driven by protein aggregation has been found to be critical for antibiotic persistence in recent years. However, our current understanding of the endogenous genes that affects dormancy depth remains limited. Here, we discovered a novel role of phage shock protein A (pspA) gene in modulating bacterial dormancy depth. Deletion of pspA of Escherichia coli resulted in increased bacterial dormancy depths and prolonged lag times for resuscitation during the stationary phase. ∆pspA exhibited a higher persister ratio compared to the wild type when challenged with various antibiotics. Microscopic images revealed that ∆pspA showed accelerated formation of protein aggresomes, which were collections of endogenous protein aggregates. Time-lapse imaging established the positive correlation between protein aggregation and antibiotic persistence of ∆pspA at the single-cell level. To investigate the molecular mechanism underlying accelerated protein aggregation, we performed transcriptome profiling and found the increased abundance of chaperons and a general metabolic slowdown in the absence of pspA. Consistent with the transcriptomic results, the ∆pspA strain showed a decreased cellular ATP level, which could be rescued by glucose supplementation. Then, we verified that replenishment of cellular ATP levels by adding glucose could inhibit protein aggregation and reduce persister formation in ∆pspA. This study highlights the novel role of pspA in maintaining proteostasis, regulating dormancy depth, and affecting antibiotic persistence during stationary phase.

Emergence of multiple fluconazole-resistant Candida parapsilosis sensu stricto clones with persistence and transmission in China.

OBJECTIVES: We explored the epidemiological and molecular characteristics of Candida parapsilosis sensu stricto isolates in China, and their mechanisms of azole resistance. METHODS: Azole susceptibilities of 2318 non-duplicate isolates were determined using CLSI broth microdilution. Isolates were genotyped by a microsatellite typing method. Molecular resistance mechanisms were also studied and functionally validated by CRISPR/Cas9-based genetic alterations. RESULTS: Fluconazole resistance occurred in 2.4% (n = 56) of isolates, and these isolates showed a higher frequency of distribution in ICU inpatients compared with susceptible isolates (48.2%, n = 27/56 versus 27.8%, 613/2208; P = 0.019). Microsatellite-genotyping analysis yielded 29 genotypes among 56 fluconazole-resistant isolates, of which 10 genotypes, including 37 isolates, belonged to clusters, persisting and transmitting in Chinese hospitals for 1-29 months. Clusters harbouring Erg11Y132F (5/10; 50%) were predominant in China. Among these, the second most dominant cluster MT07, including seven isolates, characteristically harbouring Erg11Y132F and Mrr1Q625K, lent its carriage to being one of the strongest associations with cross-resistance and high MICs of fluconazole (>256 mg/L) and voriconazole (2-8 mg/L), causing transmission across two hospitals. Among mutations tested, Mrr1Q625K led to the highest-level increase of fluconazole MIC (32-fold), while mutations located within or near the predicted transcription factor domain of Tac1 (D440Y, T492M and L518F) conferred cross-resistance to azoles. CONCLUSIONS: This study is the first Chinese report of persistence and transmissions of multiple fluconazole-resistant C. parapsilosis sensu stricto clones harbouring Erg11Y132F, and the first demonstration of the mutations Erg11G307A, Mrr1Q625K, Tac1L263S, Tac1D440Y and Tac1T492M as conferring resistance to azoles.

Outcomes of pessary fitting trials for patients with stage IV pelvic organ prolapse: a prospective study.

INTRODUCTION AND HYPOTHESIS: The objective was to evaluate the efficacy of pessaries in the treatment of stage IV pelvic organ prolapse (POP) and identify the influencing factors. METHODS: One hundred and fifty-seven patients with stage IV symptomatic POP were admitted to the hospital for pessary fitting. A successful pessary fitting was defined as a patient fitted with a pessary at the initial fitting in whom use continued 2 weeks later. The rates of successful pessary fitting, patient satisfaction, remission of prolapse and urinary symptoms, and the occurrence of factors associated with successful pessary fitting were calculated and predictors of appropriate pessary type selection were analyzed. RESULTS: A total of 130 patients with stage IV POP had a successful pessary fitting (82.8%). The satisfaction rate associated with the two types of pessaries was more than 90%. The success rate among patients undergoing a ring pessary fitting trial was 44.6%, and 84.3% of the patients were self-managed. Prolapse symptoms significantly improved in 90% of cases, and urinary symptoms improved in 58-93% of cases from baseline. The number of vaginal deliveries, history of hysterectomy and vaginal introitus/total vaginal length (TVL) ratio were independent risk factors associated with unsuccessful pessary fitting. CONCLUSION: For patients with stage IV POP, the successful fitting rate is as high as 80% or more. More vaginal deliveries, a history of hysterectomy, and a larger vaginal introitus/TVL ratio (ratio >0.6) were predictors of unsuccessful pessary fitting.

The first established microsatellite markers to distinguish Candida orthopsilosis isolates and detection of a nosocomial outbreak in China.

The infection proportion of Candida orthopsilosis, a member of the C. parapsilosis complex, has increased globally in recent years, and nosocomial outbreaks have been reported in several countries. This study aimed to establish microsatellite loci-based typing method that was able to effectively distinguish among C. orthopsilosis isolates. Three reference C. orthopsilosis genome sequences were analyzed to identify repeat loci. DNA sequences containing over eight bi- or more nucleotide repeats were selected. A total of 51 loci were initially identified, and locus-specific primers were designed and tested with 20 epidemiologically unrelated isolates. Four loci with excellent reproducibility, specificity, and resolution for molecular typing purposes were identified, and the combined discriminatory power (DP, based on 20 epidemiologically unrelated isolates) of these four loci was 1.0. Reproducibility was demonstrated by consistently testing three strains each in triplicate, and stability, demonstrated by testing 10 successive passages. Then, we collected 48 C. orthopsilosis non-duplicate clinical isolates from the China Hospital Invasive Fungal Surveillance Net study to compare the DP of the microsatellite-based typing with internal transcribed spacer (ITS) and amplified fragment length polymorphism (AFLP) typing analyses, using ATCC 96139 as a reference strain. These 49 isolates were subdivided into 12 microsatellite types (COMT1-12), six AFLP types, and three ITS types, while all the isolates with the same COMT belonged to consistent AFLP and ITS type, demonstrating the high DP of our microsatellite-type method. According to our results, COMT12 was found to be the predominant type in China, and COMT5 was the second largest and responsible for causing a nosocomial outbreak. This microsatellite-type method is a valuable tool for the differentiation of C. orthopsilosis and could be vital for epidemiological studies to determine strain relatedness and monitor transmission.

A Transformer-Based Bridge Structural Response Prediction Framework.

Structural response prediction with desirable accuracy is considerably essential for the health monitoring of bridges. However, it appears to be difficult in accurately extracting structural response features on account of complex on-site environment and noise disturbance, resulting in poor prediction accuracy of the response values. To address this issue, a Transformer-based bridge structural response prediction framework was proposed in this paper. The framework contains multi-layer encoder modules and attention modules that can precisely capture the history-dependent features in time-series data. The effectiveness of the proposed method was validated with the use of six-month strain response data of a concrete bridge, and the results are also compared with those of the most commonly used Long Short-Term Memory (LSTM)-based structural response prediction framework. The analysis indicated that the proposed method was effective in predicting structural response, with the prediction error less than 50% of the LSTM-based framework. The proposed method can be applied in damage diagnosis and disaster warning of bridges.

Silencing UHRF1 enhances cell autophagy to prevent articular chondrocytes from apoptosis in osteoarthritis through PI3K/AKT/mTOR signaling pathway.

Osteoarthritis (OA) is a common chronic degenerative joint disease, and chondrocyte apoptosis is one of most important pathological changes of OA pathogenesis. Growing studies have shown that Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is an important epigenetic regulatory factor that regulates cell proliferation and apoptosis of various tumors, but its role in OA remains ill-defined. In the present study, we found that UHRF1 expression was increased in human OA cartilage tissues, compared with normal cartilage tissues. Interleukin-1ß (IL-1ß), a major inflammatory cytokine that promotes cartilage degradation in OA, was used to stimulate primary human chondrocytes in vitro. The expression of UHRF1 was also enhanced in IL-1ß-induced chondrocytes. Moreover, down-regulation of UHRF1 induced an increase on cell proliferation and autophagy, and a decrease on apoptosis of chondrocytes after IL-1ß treatment. Further data indicated that silencing UHRF1 attenuated the up-regulation of IL-1ß on phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway in chondrocytes. Then, an activator of PI3K weakened the effect of UHRF1 silencing on cell proliferation, autophagy, apoptosis of IL-1ß-induced chondrocytes, and the cell autophagy special inhibitor 3-methyladenine (3-MA) also showed a same impact on UHRF1, hence suggesting that knockdown of UHRF1 enhances cell autophagy to protect chondrocytes from apoptosis in OA through PI3K/AKT/mTOR signaling pathway. In conclusion, our study suggests that UHRF1 may be a potential regulator of chondrocyte apoptosis in the pathogenesis of OA.

Integrated Metabolome and Transcriptome Analysis Provide Insights into the Effects of Grafting on Fruit Flavor of Cucumber with Different Rootstocks.

Rootstocks frequently exert detrimental effects on the fruit quality of grafted cucumber (Cucumis sativus L.) plants. To understand and ultimately correct this deficiency, a transcriptomic and metabolomic comparative analysis was performed among cucumber fruits from non-grafted plants (NG), and fruits from plants grafted onto different rootstocks of No.96 and No.45 (Cucurbita moschata. Duch), known to confer a different aroma and taste. We found remarkable changes in the primary metabolites of sugars, organic acids, amino acids, and alcohols in the fruit of the grafted cucumber plants with different rootstocks, compared to the non-grafted ones, especially No.45. We identified 140, 131, and 244 differentially expressed genes (DEGs) in the comparisons of GNo.96 vs. NG, GNo.45 vs. NG, and GNo.45 vs. GNo.96. The identified DEGs have functions involved in many metabolic processes, such as starch and sucrose metabolism; the biosynthesis of diterpenoid, carotenoid, and zeatin compounds; and plant hormone signal transduction. Members of the HSF, AP2/ERF-ERF, HB-HD-ZIP, and MYB transcription factor families were triggered in the grafted cucumbers, especially in the cucumber grafted on No.96. Based on a correlation analysis of the relationships between the metabolites and genes, we screened 10 candidate genes likely to be involved in sugar metabolism (Fructose-6-phosphate and trehalose), linoleic acid, and amino-acid (isoleucine, proline, and valine) biosynthesis in grafted cucumbers, and then confirmed the gene expression patterns of these genes by qRT-PCR. The levels of TPS15 (Csa3G040850) were remarkably increased in cucumber fruit with No.96 rootstock compared with No.45, suggesting changes in the volatile chemical production. Together, the results of this study improve our understanding of flavor changes in grafted cucumbers, and identify the candidate genes involved in this process.

The precise regulation of different COR genes by individual CBF transcription factors in Arabidopsis thaliana.

The transcription factors CBF1/2/3 are reported to play a dominant role in the cold responsive network of Arabidopsis by directly regulating the expression levels of cold responsive (COR) genes. In this study, we obtained CRISPR/Cas9-mediated loss-of-function mutants of cbf1∼3. Over 3,000 COR genes identified by RNA-seq analysis showed a slight but significant change in their expression levels in the mutants compared to the wild-type plants after being treated at 4 °C for 12 h. The C-repeat (CRT) motif (5'-CCGAC-3') was enriched in promoters of genes that were up-regulated by CBF2 and CBF3 but not in promoters of genes up-regulated by CBF1. These data suggest that CBF2 and CBF3 play a more important role in directing the cold response by regulating different sets of downstream COR genes. More than 2/3 of COR genes were co-regulated by two or three CBFs and were involved mainly in cellular signal transduction and metabolic processes; less than 1/3 of the genes were regulated by one CBF, and those genes up-regulated were enriched in cold-related abiotic stress responses. Our results indicate that CBFs play an important role in the trade-off between cold tolerance and plant growth through the precise regulation of COR genes in the complicated transcriptional network.

Iron and copper as virulence modulators in human fungal pathogens.

Fungal pathogens have evolved sophisticated machinery to precisely balance the fine line between acquiring essential metals and defending against metal toxicity. Iron and copper are essential metals for many processes in both fungal pathogens and their mammalian hosts, but reduce viability when present in excess. However, during infection, the host uses these two metals differently. Fe has a long-standing history of influencing virulence in pathogenic fungi, mostly in regards to Fe acquisition. Numerous studies demonstrate the requirement of the Fe acquisition pathway of Candida, Cryptococcus and Aspergillus for successful systemic infection. Fe is not free in the host, but is associated with Fe-binding proteins, leading fungi to develop mechanisms to interact with and to acquire Fe from these Fe-bound proteins. Cu is also essential for cell growth and development. Essential Cu-binding proteins include Fe transporters, superoxide dismutase (SOD) and cytochrome c oxidase. Although Cu acquisition plays critical roles in fungal survival in the host, recent work has revealed that Cu detoxification is extremely important. Here, we review fungal responses to altered metal conditions presented by the host, contrast the roles of Fe and Cu during infection, and outline the critical roles of fungal metal homeostasis machinery at the host-pathogen axis.

Interplay between acetylation and ubiquitination of imitation switch chromatin remodeler Isw1 confers multidrug resistance in Cryptococcus neoformans.

Cryptococcus neoformans poses a threat to human health, but anticryptococcal therapy is hampered by the emergence of drug resistance, whose underlying mechanisms remain poorly understood. Herein, we discovered that Isw1, an imitation switch chromatin remodeling ATPase, functions as a master modulator of genes responsible for in vivo and in vitro multidrug resistance in C. neoformans. Cells with the disrupted ISW1 gene exhibited profound resistance to multiple antifungal drugs. Mass spectrometry analysis revealed that Isw1 is both acetylated and ubiquitinated, suggesting that an interplay between these two modification events exists to govern Isw1 function. Mutagenesis studies of acetylation and ubiquitination sites revealed that the acetylation status of Isw1K97 coordinates with its ubiquitination processes at Isw1K113 and Isw1K441 through modulating the interaction between Isw1 and Cdc4, an E3 ligase. Additionally, clinical isolates of C. neoformans overexpressing the degradation-resistant ISW1K97Q allele showed impaired drug-resistant phenotypes. Collectively, our studies revealed a sophisticated acetylation-Isw1-ubiquitination regulation axis that controls multidrug resistance in C. neoformans.

Efficacy and safety of transvaginal mesh repair in a cohort with a minimum of 10-year follow-up.

Although transvaginal mesh (TVM) repair is no longer used in some countries, long-term outcomes after TVM surgery are of great importance globally. However, reports with follow-up >10 years are limited. Thus, this study aimed to report outcomes in a prospective cohort with at least 10 years of follow-up. Women with stage III-IV symptomatic prolapse were approached consecutively from 2008 to 2013 at one tertiary hospital. The main outcome measure was symptomatic failure. Secondary outcomes included anatomic failure, recurrence, patient satisfaction, complications, and reoperation. The Kaplan-Meier curve was used to estimate the cumulative failure rate. Of the 121 patients enrolled in the study, 103 (85.1%) completed a median follow-up of 11 years. The estimated probability rates of symptomatic and anatomic failure were 17.6% and 8.8% in 11 years, respectively. The estimated incidence of symptomatic failure increased by 8.2% between 5 and 11 years; however, the corresponding rate for anatomic failure was 3.7%. The most common complication was vaginal mesh exposure, and its estimated probability increased from 19.3% to 28.4% from 5 to 11 years, respectively. Office trimming resolved 80.0% of vaginal exposures. These patients did not report decreased overall satisfaction. Patients with vaginal mesh exposure requiring>3 office procedures or mesh removal in the operating room (5.8% by 11 years) had lower satisfaction rates (P<0.01) and were defined as having severe mesh exposure. The rates of postoperative pain, reoperation, and Patient Global Impression of Improvement ⩾2 were 2.5%, 3.3%, and 94.2%, respectively. The results of this study implied that TVM treatment gradually increased the symptomatic failure rate but provided durable anatomical support of the vaginal wall. Vaginal mesh exposure was common in women who were largely not sexually active; however, 80% of the cases could be managed in the outpatient clinic, which did not affect patient satisfaction.

Unraveling the mechanism of thermotolerance by Set302 in Cryptococcus neoformans.

The underlying mechanism of thermotolerance, which is a key virulence factor essential for pathogenic fungi such as Cryptococcus neoformans, is largely unexplored. In this study, our findings suggest that Set302, a homolog of Set3 and a subunit of histone deacetylase complex Set3C, contributes to thermotolerance in C. neoformans. Specifically, the deletion of the predicted Set3C core subunit, Set302, resulted in further reduction in the growth of C. neoformans at 39°C, and survival of transient incubation at 50°C. Transcriptomics analysis revealed that the expression levels of numerous heat stress-responsive genes altered at both 30°C and 39°C due to the lack of Set302. Notably, at 39°C, the absence of Set302 led to the downregulation of gene expression related to the ubiquitin-proteasome system (UPS). Based on the GFP-α-synuclein overexpression model to characterize misfolded proteins, we observed a pronounced accumulation of misfolded GFP-α-synuclein at 39°C, consequently inhibiting C. neoformans thermotolerance. Furthermore, the loss of Set302 exacerbated the accumulation of misfolded GFP-α-synuclein during heat stress. Interestingly, the set302∆ strain exhibited a similar phenotype under proteasome stress as it did at 39°C. Moreover, the absence of Set302 led to reduced production of capsule and melanin. set302∆ strain also displayed significantly reduced pathogenicity and colonization ability compared to the wild-type strain in the murine infection model. Collectively, our findings suggest that Set302 modulates thermotolerance by affecting the degradation of misfolded proteins and multiple virulence factors to mediate the pathogenicity of C. neoformans.IMPORTANCECryptococcus neoformans is a pathogenic fungus that poses a potential and significant threat to public health. Thermotolerance plays a crucial role in the wide distribution in natural environments and host colonization of this fungus. Herein, Set302, a critical core subunit for the integrity of histone deacetylase complex Set3C and widely distributed in various fungi and mammals, governs thermotolerance and affects survival at extreme temperatures as well as the formation of capsule and melanin in C. neoformans. Additionally, Set302 participates in regulating the expression of multiple genes associated with the ubiquitin-proteasome system (UPS). By eliminating misfolded proteins under heat stress, Set302 significantly contributes to the thermotolerance of C. neoformans. Moreover, Set302 regulates the pathogenicity and colonization ability of C. neoformans in a murine model. Overall, this study provides new insight into the mechanism of thermotolerance in C. neoformans.

Natural variation of C-repeat-binding factor (CBFs) genes is a major cause of divergence in freezing tolerance among a group of Arabidopsis thaliana populations along the Yangtze River in China.

We used a monophyletic group of four natural populations of Arabidopsis thaliana expanded from a single ancestor along the Yangtze River c. 90,000 yr ago to study the molecular mechanism of the divergence in their freezing tolerance, in order to gain an insight into the genetic basis of their local adaption to low temperatures. Freezing tolerance assays, measurements of metabolites in the raffinose biosynthesis pathway and transactivation-activity assays of variation in forms of cold-responsive transcription factors were conducted on the four populations. Quantitative trait locus mapping was adopted with F2 populations of the most- and least freezing-tolerant populations. The degree of freezing tolerance among the four populations was negatively correlated with the lowest monthly average temperature of January in their native habitats, and positively correlated to the expression level of some cold-regulated genes. We identified a major locus harboring three cold-responsive transcription factor genes CBF1-3, and found a nucleotide insertion in CBF2 in all populations except SXcgx, which generated a dysfunctional CBF2 protein. The CBF2 in SXcgx experienced a stronger natural selection in the cooler environment after CBF3 lost its response to low temperature, which possibly reflects a local adaptation of these populations during the expansion from a common ancestor.

The function and regulation of heat shock transcription factor in Cryptococcus.

Cryptococcus species are opportunistic human fungal pathogens. Survival in a hostile environment, such as the elevated body temperatures of transmitting animals and humans, is crucial for Cryptococcus infection. Numerous intriguing investigations have shown that the Hsf family of thermotolerance transcription regulators plays a crucial role in the pathogen-host axis of Cryptococcus. Although Hsf1 is known to be a master regulator of the heat shock response through the activation of gene expression of heat shock proteins (Hsps). Hsf1 and other Hsfs are multifaceted transcription regulators that regulate the expression of genes involved in protein chaperones, metabolism, cell signal transduction, and the electron transfer chain. In Saccharomyces cerevisiae, a model organism, Hsf1's working mechanism has been intensively examined. Nonetheless, the link between Hsfs and Cryptococcus pathogenicity remains poorly understood. This review will focus on the transcriptional regulation of Hsf function in Cryptococcus, as well as potential antifungal treatments targeting Hsf proteins.

Subculturing and Gram staining of blood cultures flagged negative by the BACTEC™ FX system: Optimizing the workflow for detection of Cryptococcus neoformans in clinical specimens.

Objective: To investigate whether an incubation time of 5 days (Aerobic/F, Anaerobic/F) and 14 days (Myco/F) blood culture bottles is sufficient to prevent false-negative results. Methods: We evaluated 1,244 blood bottles (344 patients) defined as negative by the BACTEC™ FX system. We also reviewed published cases and our own cases of bloodstream infection caused by Cryptococcus neoformans and simulated different scenarios, including different inoculation concentrations, bottle types, and clinical isolates. Results: Two bottles (0.16%) were found to contain C. neoformans when subcultured and Gram stained. A 5-day protocol with Aerobic/F bottles was insufficient for the growth of C. neoformans in some cases, and C. neoformans grew better in Myco/F bottles than in Aerobic/F bottles. Conclusion: Subculturing and Gram staining after a 5-day protocol were important for the detection of C. neoformans, and Myco/F bottles should be collected for the blood culture of C. neoformans.

Ultrafast and facile construction of programmable, multidimensional wrinkled-patterned polyacrylamide/sodium alginate hydrogels for human skin-like tactile perception.

Customizable structures and patterns are becoming powerful tools for biomimetic design and application of soft materials. The construction of long-range ordered self-wrinkled structures on multi-dimensional and complex-shaped surfaces with facile, fast and efficient strategies still faces serious challenges. During the stretch-recovery process, the carboxyl groups in the polyacrylamide/sodium alginate dual network gel form robust coordination with Fe3+ to achieve a hard shell layer, resulting in a modulus mismatch between the inner soft layer and the outer hard layer, thereby forming a wrinkled surface. This flexible strategy allows simultaneous construction of complex topologies from 1D to 3D wits well-organized microstructure and controllable dimensions. The mechanism of the influence of ion treating time and pre-stretching ratio on wrinkle wavelength was explored in detail. The finite element simulations matched well with the experimental results. Due to the unique surface and dual crosslinking network, the self-wrinkled hydrogel maintains a high sensitivity of up to 67.47 kPa-1 in 1000 compression cycles. As a high-sensitivity pressure sensor integrated into the detection system, it can be efficiently applied to the contact dynamic tactile perception and monitoring of various movement behaviors of the human body.

Immunization with a heat-killed prm1 deletion strain protects the host from Cryptococcus neoformans infection.

Systemic infection with Cryptococcus neoformans, a dangerous and contagious pathogen found throughout the world, frequently results in lethal cryptococcal pneumonia and meningoencephalitis, and no effective treatments and vaccination of cryptococcosis are available. Here, we describe Prm1, a novel regulator of C. neoformans virulence. C. neoformans prm1Δ cells exhibit extreme sensitivity to various environmental stress conditions. Furthermore, prm1Δ cells show deficiencies in the biosynthesis of chitosan and mannoprotein, which in turn result in impairment of cell wall integrity. Treatment of mice with heat-killed prm1Δ cells was found to facilitate the host immunological defence against infection with wild-type C. neoformans. Further investigation demonstrated that prm1Δ cells strongly promote pulmonary production of interferon-γ, leading to activation of macrophage M1 differentiation and inhibition of M2 polarization. Therefore, our findings suggest that C. neoformans Prm1 may be a viable target for the development of anti-cryptococcosis medications and, cells lacking Prm1 represent a promising candidate for a vaccine.

Study of an antifungal medicine isavuconazole used in treatment of mold infections in China: A plain language summary.

WHAT IS THIS SUMMARY ABOUT?: Molds are types of fungus that can cause sickness and death. Mold infections are increasing in China. Until 2022, medicines that can effectively treat all mold infections were still lacking in China. This summary of a study originally published in the journal Infection and Drug Resistance. The study took place in China and tested a medicine called isavuconazole on mold samples to check if isavuconazole can be used to treat mold infections. Isavuconazole became available in China in January 2022 as a capsule (a hard gel-covered pill filled with a dose of medicine) and in June 2022 as an injection or a shot. WHAT WERE THE RESULTS?: Isavuconazole stopped the growth of most molds. Other medicines were needed at higher amounts to stop the growth of molds. WHAT DO THE RESULTS OF THE STUDY MEAN?: Isavuconazole is another option to treat mold infections in China.

A-to-I RNA Editing in Klebsiella pneumoniae Regulates Quorum Sensing and Affects Cell Growth and Virulence.

Millions of adenosine (A) to inosine (I) RNA editing events are reported and well-studied in eukaryotes; however, many features and functions remain unclear in prokaryotes. By combining PacBio Sequel, Illumina whole-genome sequencing, and RNA Sequencing data of two Klebsiella pneumoniae strains with different virulence, a total of 13 RNA editing events are identified. The RNA editing event of badR is focused, which shows a significant difference in editing levels in the two K. pneumoniae strains and is predicted to be a transcription factor. A hard-coded Cys is mutated on DNA to simulate the effect of complete editing of badR. Transcriptome analysis identifies the cellular quorum sensing (QS) pathway as the most dramatic change, demonstrating the dynamic regulation of RNA editing on badR related to coordinated collective behavior. Indeed, a significant difference in autoinducer 2 activity and cell growth is detected when the cells reach the stationary phase. Additionally, the mutant strain shows significantly lower virulence than the WT strain in the Galleria mellonella infection model. Furthermore, RNA editing regulation of badR is highly conserved across K. pneumoniae strains. Overall, this work provides new insights into posttranscriptional regulation in bacteria.

Improving photosynthetic efficiency toward food security: Strategies, advances, and perspectives.

Photosynthesis in crops and natural vegetation allows light energy to be converted into chemical energy and thus forms the foundation for almost all terrestrial trophic networks on Earth. The efficiency of photosynthetic energy conversion plays a crucial role in determining the portion of incident solar radiation that can be used to generate plant biomass throughout a growth season. Consequently, alongside the factors such as resource availability, crop management, crop selection, maintenance costs, and intrinsic yield potential, photosynthetic energy use efficiency significantly influences crop yield. Photosynthetic efficiency is relevant to sustainability and food security because it affects water use efficiency, nutrient use efficiency, and land use efficiency. This review focuses specifically on the potential for improvements in photosynthetic efficiency to drive a sustainable increase in crop yields. We discuss bypassing photorespiration, enhancing light use efficiency, harnessing natural variation in photosynthetic parameters for breeding purposes, and adopting new-to-nature approaches that show promise for achieving unprecedented gains in photosynthetic efficiency.