The mitochondrial carboxylase PCCA interacts with Listeria monocytogenes phospholipase PlcB to modulate bacterial survival.

Listeria monocytogenes, a prominent foodborne pathogen responsible for zoonotic infections, owes a significant portion of its virulence to the presence of the phospholipase PlcB. In this study, we performed an in-depth examination of the intricate relationship between L. monocytogenes PlcB and host cell mitochondria, unveiling a novel participant in bacterial survival: the mitochondrial carboxylase propionyl-coenzyme A carboxylase (PCCA). Our investigation uncovered previously unexplored levels of interaction and colocalization between PCCA and PlcB within host cells, with particular emphasis on the amino acids 504-508 of PCCA, which play a pivotal role in this partnership. To assess the effect of PCCA expression on L. monocytogenes proliferation, PCCA expression levels were manipulated by siRNA-si-PCCA or pCMV-N-HA-PCCA plasmid transfection. Our findings demonstrated a clear inverse correlation between PCCA expression levels and the proliferation of L. monocytogenes. Furthermore, the effect of L. monocytogenes infection on PCCA expression was investigated by assessing PCCA mRNA and protein expression in HeLa cells infected with L. monocytogenes. These results indicate that L. monocytogenes infection did not significantly alter PCCA expression. These findings led us to propose that PCCA represents a novel participant in L. monocytogenes survival, and its abundance has a detrimental impact on bacterial proliferation. This suggests that L. monocytogenes may employ PlcB-PCCA interactions to maintain stable PCCA expression, representing a unique pro-survival strategy distinct from that of other intracellular bacterial pathogens. IMPORTANCE: Mitochondria represent attractive targets for pathogenic bacteria seeking to modulate host cellular processes to promote their survival and replication. Our current study has uncovered mitochondrial carboxylase propionyl-coenzyme A carboxylase (PCCA) as a novel host cell protein that interacts with L. monocytogenes PlcB. The results demonstrate that PCCA plays a negative regulatory role in L. monocytogenes infection, as heightened PCCA levels are associated with reduced bacterial survival and persistence. However, L. monocytogenes may exploit the PlcB-PCCA interaction to maintain stable PCCA expression and establish a favorable intracellular milieu for bacterial infection. Our findings shed new light on the intricate interplay between bacterial pathogens and host cell mitochondria, while also highlighting the potential of mitochondrial metabolic enzymes as antimicrobial agents.

TGF ß1 promotes the polarization of M2-type macrophages and activates PI3K/mTOR signaling pathway by inhibiting ISG20 to sensitize ovarian cancer to cisplatin.

The involvement of Interferon-stimulated exonuclease gene 20 (ISG20) has been reported in renal clear cell carcinoma, hepatocellular carcinoma, and cervical cancer. However, its role in ovarian cancer chemotherapy remains unclear. In this study, we conducted a comparative analysis of TGF-ß1 and ISG20 in cisplatin-sensitive and cisplatin-resistant ovarian cancer cells and tissues using qRT-PCR and a tissue immunofluorescence analysis. We also investigated the impact of ISG20-targeted drugs (IFN-γ) and TGF-ß1 inhibitors on cisplatin response both in vivo and in vitro. Additionally, we assessed the effects of TGF-ß1 or ISG20 on the polarization of tumor-associated macrophages through flow cytometry and ELISA analysis. Our findings revealed that ISG20 expression was lower in cisplatin-resistant tissues compared to cisplatin-sensitive tissues; however, overexpression of ISG20 sensitized ovarian cancer to cisplatin treatment. Furthermore, activation of ISG20 expression with IFN-γ or TGF-ß1 inhibitors enhanced the sensitivity of ovarian cancer cells to cisplatin therapy. Notably, our results demonstrated that TGF-ß1 promoted M2-type macrophage polarization as well as PI3K/mTOR pathway activation by suppressing ISG20 expression both in vivo and in vitro. In conclusion, our study highlights the critical role played by ISG20 within the network underlying cisplatin resistance in ovarian cancer. Targeting ISG20 using IFN-γ or TGF-ß1 inhibitors may represent a promising therapeutic strategy for treating ovarian cancer.

The R2R3-MYB transcription factor ZeMYB32 negatively regulates anthocyanin biosynthesis in Zinnia elegans.

KEY MESSAGE: This study identified an R2R3-MYB from Zinnia elegans, ZeMYB32, which negatively regulates anthocyanin biosynthesis.

Microplastics dampen the self-renewal of hematopoietic stem cells by disrupting the gut microbiota-hypoxanthine-Wnt axis.

Microplastics (MPs) are contaminants ubiquitously found in the global biosphere that enter the body through inhalation or ingestion, posing significant risks to human health. Recent studies emerge that MPs are present in the bone marrow and damage the hematopoietic system. However, it remains largely elusive about the specific mechanisms by which MPs affect hematopoietic stem cells (HSCs) and their clinical relevance in HSC transplantation (HSCT). Here, we established a long-term MPs intake mouse model and found that MPs caused severe damage to the hematopoietic system. Oral gavage administration of MPs or fecal transplantation of microbiota from MPs-treated mice markedly undermined the self-renewal and reconstitution capacities of HSCs. Mechanistically, MPs did not directly kill HSCs but disrupted gut structure and permeability, which eventually ameliorated the abundance of Rikenellaceae and hypoxanthine in the intestine and inactivated the HPRT-Wnt signaling in bone marrow HSCs. Furthermore, administration of Rikenellaceae or hypoxanthine in mice as well as treatment of WNT10A in the culture system substantially rescued the MPs-induced HSC defects. Finally, we validated in a cohort of human patients receiving allogenic HSCT from healthy donors, and revealed that the survival time of patients was negatively correlated with levels of MPs, while positively with the abundance of Rikenellaceae, and hypoxanthine in the HSC donors' feces and blood. Overall, our study unleashes the detrimental roles and mechanisms of MPs in HSCs, which provides potential strategies to prevent hematopoietic damage from MPs and serves as a fundamental critique for selecting suitable donors for HSCT in clinical practice.

Rice receptor kinase FLR7 regulates rhizosphere oxygen levels and enriches the dominant Anaeromyxobacter that improves submergence tolerance in rice.

Oxygen is one of the determinants of root microbiome formation. However, whether plants regulate rhizosphere oxygen levels to affect microbiota composition and the underlying molecular mechanisms remain elusive. The receptor-like kinase (RLK) family member FERONIA modulates the growth-defense tradeoff in Arabidopsis. Here, we established that rice FERONIA-like RLK 7 (FLR7) controls rhizosphere oxygen levels by methylene blue staining, oxygen flux, and potential measurements. The formation of oxygen-transporting aerenchyma in roots is negatively regulated by FLR7. We further characterized the root microbiota of 11 FLR mutants including flr7 and wild-type Nipponbare (Nip) grown in the field by 16S ribosomal RNA gene profiling and demonstrated that the 11 FLRs are involved in regulating rice root microbiome formation. The most abundant anaerobic-dependent genus Anaeromyxobacter in the Nip root microbiota was less abundant in the root microbiota of all these mutants, and this contributed the most to the community differences between most mutants and Nip. Metagenomic sequencing revealed that flr7 increases aerobic respiration and decreases anaerobic respiration in the root microbiome. Finally, we showed that a representative Anaeromyxobacter strain improved submergence tolerance in rice via FLR7. Collectively, our findings indicate that FLR7 mediates changes in rhizosphere oxygen levels and enriches the beneficial dominant genus Anaeromyxobacter and may provide insights for developing plant flood prevention strategies via the use of environment-specific functional soil microorganisms.

Single-cell RNA sequencing reveals the immunoregulatory roles of PegIFN-α in patients with chronic hepatitis B.

BACKGROUND AND AIMS: Chronic hepatitis B (CHB) is caused by HBV infection and affects the lives of millions of people worldwide by causing liver inflammation, cirrhosis, and liver cancer. Interferon-alpha (IFN-α) therapy is a conventional immunotherapy that has been widely used in CHB treatment and achieved promising therapeutic outcomes by activating viral sensors and interferon-stimulated genes (ISGs) suppressed by HBV. However, the longitudinal landscape of immune cells of CHB patients and the effect of IFN-α on the immune system are not fully understood. APPROACH AND RESULTS: Here, we applied single-cell RNA sequencing (scRNA-seq) to delineate the transcriptomic landscape of peripheral immune cells in CHB patients before and after PegIFN-α therapy. Notably, we identified three CHB-specific cell subsets, pro-inflammatory (Pro-infla) CD14+ monocytes, Pro-infla CD16+ monocytes and IFNG+ CX3CR1- NK cells, which highly expressed proinflammatory genes and positively correlated with HBsAg. Furthermore, PegIFN-α treatment attenuated percentages of hyperactivated monocytes, increased ratios of long-lived naive/memory T cells and enhanced effector T cell cytotoxicity. Finally, PegIFN-α treatment switched the transcriptional profiles of entire immune cells from TNF-driven to IFN-α-driven pattern and enhanced innate antiviral response, including virus sensing and antigen presentation. CONCLUSIONS: Collectively, our study expands the understanding of the pathological characteristics of CHB and the immunoregulatory roles of PegIFN-α, which provides a new powerful reference for the clinical diagnosis and treatment of CHB.

A Modified Suture Technique to Improve Scar Appearance in Wounds Under High Tension.

ABSTRACT: The purpose of this study was to introduce a modified suture technique and to compare its effects on skin scar formation with 2 traditional suture methods: simple interrupted suture (SIS) and vertical mattress suture (VMS). Three groups of healthy adult female Sprague-Dawley rats were selected (6 replicates in each group), and the full-thickness skin of 5 cm × 0.2 cm was cut off on the back of the rats after anesthesia. The wounds were then sutured using 1 of the 3 methods for each group: SIS, VMS, and a newly introduced modified vertical mattress suture (M-VMS) technique with the needle reinsertion at the exit point. A traction device was installed on the back of the rats to achieve high tension wounds. The tensile distance was increased by 1 mm every day for 20 days. After 20 days of healing, the hematoxylin-eosin staining method was used for observation of scar morphology. The collagen production rate was measured by Masson staining, and the type I collagen and type III collagen were detected by the immunofluorescence method. Immunohistochemical staining was used to detect the expression of myofibroblast marker α-smooth muscle actin, and real-time quantitative polymerase chain reaction and Western blot techniques were used to detect the expressions of transforming growth factors TGFß1, TGFß2, and TGFß3 to understand the mechanisms of scar formation. Results showed that the quantity and density of collagen fibers were both lower in the M-VMS group than in the other 2 groups. Immunofluorescence results showed that type I collagen was significantly lower, whereas type III collagen was significantly higher in the M-VMS group than in the other 2 groups. The expressions of α-smooth muscle actin and TGFß1 both were lower in the M-VMS group than in the other 2 groups. The expression of TGFß2 and TGFß3 had no obvious difference among the 3 groups. For wounds under high tension, compared with SIS and VMS methods, the M-VMS technique we proposed can reduce scar formation due to the reduction of collagen formation, myofibroblast expression, and TGFß1 expression.

Genome-wide identification and expression patterns of the laccase gene family in response to kiwifruit bacterial canker infection.

BACKGROUND: Kiwifruit bacterial canker, caused by Pseudomonas syringae pv. actinidiae (Psa), is a destructive disease worldwide. Resistance genes that respond to Psa infection urgently need to be identified for controlling this disease. Laccase is mainly involved in the synthesis of lignin in the plant cell wall and plays a prominent role in plant growth and resistance to pathogen infection. However, the role of laccase in kiwifruit has not been reported, and whether laccase is pivotal in the response to Psa infection remains unclear. RESULTS: We conducted a bioinformatics analysis to identify 55 laccase genes (AcLAC1-AcLAC55) in the kiwifruit genome. These genes were classified into five cluster groups (I-V) based on phylogenetic analysis, with cluster groups I and II having the highest number of members. Analysis of the exon-intron structure revealed that the number of exons varied from 1 to 8, with an average of 5 introns. Our evolutionary analysis indicated that fragment duplication played a key role in the expansion of kiwifruit laccase genes. Furthermore, evolutionary pressure analysis suggested that AcLAC genes were under purifying selection. We also performed a cis-acting element analysis and found that AcLAC genes contained multiple hormone (337) and stress signal (36) elements in their promoter regions. Additionally, we investigated the expression pattern of laccase genes in kiwifruit stems and leaves infected with Psa. Our findings revealed that laccase gene expression levels in the stems were higher than those in the leaves 5 days after inoculation with Psa. Notably, AcLAC2, AcLAC4, AcLAC17, AcLAC18, AcLAC26, and AcLAC42 showed significantly higher expression levels (p < 0.001) compared to the non-inoculated control (0 d), suggesting their potential role in resisting Psa infection. Moreover, our prediction indicated that 21 kiwifruit laccase genes are regulated by miRNA397, they could potentially act as negative regulators of lignin biosynthesis. CONCLUSIONS: These results are valuable for further analysis of the resistance function and molecular mechanism of laccases in kiwifruit.

DegU-mediated suppression of carbohydrate uptake in Listeria monocytogenes increases adaptation to oxidative stress.

The foodborne bacterial pathogen Listeria monocytogenes exhibits remarkable survival capabilities under challenging conditions, severely threatening food safety and human health. The orphan regulator DegU is a pleiotropic regulator required for bacterial environmental adaptation. However, the specific mechanism of how DegU participates in oxidative stress tolerance remains unknown in L. monocytogenes. In this study, we demonstrate that DegU suppresses carbohydrate uptake under stress conditions by altering global transcriptional profiles, particularly by modulating the transcription of the phosphoenolpyruvate-carbohydrate phosphotransferase system (PTS)-related genes, such as ptsH, ptsI, and hprK. Specifically, in the absence of degU, the transcripts of ptsI are significantly upregulated and those of hprK are significantly downregulated in response to copper ion-induced stress. Overexpression of ptsI significantly increases bacterial growth in vitro, while overexpression of hprK leads to a decrease in growth. We further demonstrate that DegU directly senses oxidative stress, downregulates ptsI transcription, and upregulates hprK transcription. Additionally, through an electrophoretic mobility shift assay, we demonstrate that DegU directly regulates the transcription of ptsI and hprK by binding to specific regions within their respective promoter sequences. Notably, the putative pivotal DegU binding sequence for ptsI is located from 38 to 68 base pairs upstream of the ptsH transcription start site (TSS), whereas for hprK, it is mapped from 36 to 124 base pairs upstream of the hprK TSS. In summary, we elucidate that DegU plays a significant role in suppressing carbohydrate uptake in response to oxidative stress through the direct regulation of ptsI and hprK.ImportanceUnderstanding the adaptive mechanisms employed by Listeria monocytogenes in harsh environments is of great significance. This study focuses on investigating the role of DegU in response to oxidative stress by examining global transcriptional profiles. The results highlight the noteworthy involvement of DegU in this stress response. Specifically, DegU acts as a direct sensor of oxidative stress, leading to the modulation of gene transcription. It downregulates ptsI transcription while it upregulates hprK transcription through direct binding to their promoters. Consequently, these regulatory actions impede bacterial growth, providing a defense mechanism against stress-induced damage. These findings gained from this study may have broader implications, serving as a reference for studying adaptive mechanisms in other pathogenic bacteria and aiding in the development of targeted strategies to control L. monocytogenes and ensure food safety.

Characterization of a DsbA family protein reveals its crucial role in oxidative stress tolerance of Listeria monocytogenes.

IMPORTANCE: The adaption and tolerance to various environmental stresses are the fundamental factors for the widespread existence of Listeria monocytogenes. Anti-oxidative stress is the critical mechanism for the survival and pathogenesis of L. monocytogenes. The thioredoxin (Trx) and glutaredoxin (Grx) systems are known to contribute to the anti-oxidative stress of L. monocytogenes, but whether the Dsb system has similar roles remains unknown. This study demonstrated that the DsbA family protein Lmo1059 of L. monocytogenes participates in bacterial oxidative stress tolerance, with Cys36 as the key amino acid of its catalytic activity and anti-oxidative stress ability. It is worth noting that Lmo1059 was involved in the invading and cell-to-cell spread of L. monocytogenes. This study lays a foundation for further understanding the specific mechanisms of oxidative cysteine repair and antioxidant stress regulation of L. monocytogenes, which contributes to an in-depth understanding of the environmental adaptation mechanisms for foodborne bacterial pathogens.

A New Strategy for Bearing Health Assessment with a Dynamic Interval Prediction Model.

Bearing is the critical basic component of rotating machinery and its remaining life prediction is very important for mechanical equipment's smooth and healthy operation. However, fast and accurate bearing life prediction has always been a difficult point in industry and academia. This paper proposes a new strategy for bearing health assessment based on a model-driven dynamic interval prediction model. Firstly, the mapping proportion algorithm is used to determine whether the measured data are in the degradation stage. After finding the starting point of prediction, the improved annealing algorithm is used to determine the shortest data interval that can be used for accurate prediction. Then, based on the bearing degradation curve and the information fusion inverse health index, the health index is obtained from 36 general indexes in the time domain and frequency domain through screening, fusion, and inversion. Finally, the state space equation is constructed based on the Paris-DSSM formula and the particle filter is used to iterate the state space equation parameters with the minimum interval data to construct the life prediction model. The proposed method is verified by XJTU-SY rolling bearing life data. The results show that the prediction accuracy of the proposed strategy for the remaining life of the bearing can reach more than 90%. It is verified that the improved simulated annealing algorithm selects limited interval data, reconstructs health indicators based on bearing degradation curve and information fusion, and updates the Paris-DSSM state space equation through the particle filter algorithm. The bearing life prediction model constructed on this basis is accurate and effective.

Listeria monocytogenes GshF contributes to oxidative stress tolerance via regulation of the phosphoenolpyruvate-carbohydrate phosphotransferase system.

Glutathione (GSH) is an essential component of the glutaredoxin (Grx) system, and it is synthesized by the enzyme glutathione synthase GshF in Listeria monocytogenes. GSH plays a crucial role in regulating Listeria virulence by modifying the virulence factors LLO and PrfA. In this study, we investigated the involvement of L. monocytogenes GshF in oxidative tolerance and intracellular infection. Our findings revealed that the deletion of gshF resulted in a significant reduction in bacterial growth in vitro when exposed to diamide and copper ions stress. More importantly, this deletion also impaired the efficiency of invasion and proliferation in macrophages and mice organs. Furthermore, GshF influenced global transcriptional profiles, including carbohydrate and amino acid metabolism, particularly those related to the phosphoenolpyruvate-carbohydrate phosphotransferase system (PTS) genes lmo1997-lmo2004, under oxidative stress conditions. In the wild-type strain, the transcription of lmo1997-lmo2004 was notably downregulated in response to copper ions and diamide stress compared to normal conditions. However, in the absence of gshF, the transcripts of lmo1997-lmo2004 were upregulated in response to these stress conditions. Notably, the deletion of iiBman (lmo2002) enhanced oxidative stress tolerance to copper ions, whereas overexpression of iiBman reduced this resistance. In conclusion, our study provides the first evidence that L. monocytogenes GshF plays a crucial role in bacterial antioxidation through the regulation of iiBman.IMPORTANCEListeria monocytogenes has developed various mechanisms to withstand oxidative stress, including the thioredoxin and glutaredoxin systems. However, the specific role of the glutathione synthase GshF, responsible for synthesizing GSH in L. monocytogenes, in oxidative tolerance remains unclear. This study aimed to elucidate the relationship between GshF and oxidative tolerance in L. monocytogenes by examining the efficiency of invasion and proliferation in macrophages and mice organs, as well as analyzing global transcriptional profiles under oxidative stress conditions. The results revealed that GshF plays a significant role in L. monocytogenes' response to oxidative stress. Notably, GshF acts to suppress the transcription of phosphoenolpyruvate-carbohydrate phosphotransferase system genes lmo1997-lmo2004, among which iiBman (lmo2002) was identified as the most critical gene for resisting oxidative stress. These findings enhance our understanding of how L. monocytogenes adapts to its environment and provide valuable insights for investigating the environmental adaptation mechanisms of other pathogenic bacteria.

Hypoxia-induced HIF-1α promotes Listeria monocytogenes invasion into tilapia.

HIF-1α is a nuclear transcription factor, and its activity is tightly regulated by the level of available oxygen in cells. Here, we investigated the roles of HIF-1α in the invasion of Listeria monocytogenes into tilapia under hypoxic environments. We found that the expression levels of HIF-1α in examined tissues of hypoxic tilapia were significantly upregulated, indicating that the tissue cells have been in hypoxic conditions. After 24-h infection with L. monocytogenes, we found that bacterial burden counts increased significantly in all examined tissues of hypoxic fish. To explore why the bacterial count increased significantly in the tissues of hypoxic fish, we modulated HIF-1α expression through RNAi technology. The results indicated that c-Met expression levels were positively related to HIF-1α expression. Since c-Met is the receptor of InlB that plays critical roles in the adhesion and invasion of L. monocytogenes, the ∆InlB strain was used to further explore the reason for the significant increase in bacterial counts in hypoxic fish. As expected, the decrease in the adhesion ability of ∆InlB suggested that InlB mediates L. monocytogenes infection in tilapia. After being infected with ∆InlB strain, we found that the bacterial counts in hypoxic fish were not affected by hypoxic conditions or HIF-1α expression levels. These findings indicate that HIF-1α may promote the internalization of InlB by upregulating c-Met expression and therefore contributes to the invasion of L. monocytogenes into hypoxic tilapia. IMPORTANCE Listeria monocytogenes is a zoonotic food-borne bacterial pathogen with a solid pathogenicity for humans. After ingestion of highly contaminated food, L. monocytogenes is able to cross the intestine invading phagocytic and nonphagocytic cells and causes listeriosis. China is the world's largest supplier of tilapia. The contamination rate of L. monocytogenes to tilapia products was as high as 2.81%, causing a severe threat to public health. This study revealed the underlying regulatory mechanisms of HIF-1α in the invasion of L. monocytogenes into tilapia under hypoxic environments. This study will be helpful for better understanding the molecular mechanisms of hypoxic environments in L. monocytogenes infection to tilapia. More importantly, our data will provide novel insights into the prevention and control of this pathogen in aquaculture.

Development and application of nanomaterials, nanotechnology and nanomedicine for treating hematological malignancies.

Hematologic malignancies (HMs) pose a serious threat to patients' health and life, and the five-year overall survival of HMs remains low. The lack of understanding of the pathogenesis and the complex clinical symptoms brings immense challenges to the diagnosis and treatment of HMs. Traditional therapeutic strategies for HMs include radiotherapy, chemotherapy, targeted therapy and hematopoietic stem cell transplantation. Although immunotherapy and cell therapy have made considerable progress in the last decade, nearly half of patients still relapse or suffer from drug resistance. Recently, studies have emerged that nanomaterials, nanotechnology and nanomedicine show great promise in cancer therapy by enhancing drug targeting, reducing toxicity and side effects and boosting the immune response to promote durable immunological memory. In this review, we summarized the strategies of recently developed nanomaterials, nanotechnology and nanomedicines against HMs and then proposed emerging strategies for the future designment of nanomedicines to treat HMs based on urgent clinical needs and technological progress.

Neural grafts containing exosomes derived from Schwann cell-like cells promote peripheral nerve regeneration in rats.

Background: Schwann cell-like cells (SCLCs), differentiated from mesenchymal stem cells, have shown promising outcomes in the treatment of peripheral nerve injuries in preclinical studies. However, certain clinical obstacles limit their application. Hence, the primary aim of this study was to investigate the role of exosomes derived from SCLCs (SCLCs-exo) in peripheral nerve regeneration. Methods: SCLCs were differentiated from human amniotic mesenchymal stem cells (hAMSCs) in vitro and validated by immunofluorescence, real-time quantitative PCR and western blot analysis. Exosomes derived from hAMSCs (hAMSCs-exo) and SCLCs were isolated by ultracentrifugation and validated by nanoparticle tracking analysis, WB analysis and electron microscopy. A prefabricated nerve graft was used to deliver hAMSCs-exo or SCLCs-exo in an injured sciatic nerve rat model. The effects of hAMSCs-exo or SCLCs-exo on rat peripheral nerve injury (PNI) regeneration were determined based on the recovery of neurological function and histomorphometric variation. The effects of hAMSCs-exo or SCLCs-exo on Schwann cells were also determined via cell proliferation and migration assessment. Results: SCLCs significantly expressed the Schwann cell markers glial fibrillary acidic protein and S100. Compared to hAMSCs-exo, SCLCs-exo significantly enhanced motor function recovery, attenuated gastrocnemius muscle atrophy and facilitated axonal regrowth, myelin formation and angiogenesis in the rat model. Furthermore, hAMSCs-exo and SCLCs-exo were efficiently absorbed by Schwann cells. However, compared to hAMSCs-exo, SCLCs-exo significantly promoted the proliferation and migration of Schwann cells. SCLCs-exo also significantly upregulated the expression of a glial cell-derived neurotrophic factor, myelin positive regulators (SRY-box transcription factor 10, early growth response protein 2 and organic cation/carnitine transporter 6) and myelin proteins (myelin basic protein and myelin protein zero) in Schwann cells. Conclusions: These findings suggest that SCLCs-exo can more efficiently promote PNI regeneration than hAMSCs-exo and are a potentially novel therapeutic approach for treating PNI.

The Relationship Between Pain Intensity and Pain-Related Activity Patterns in Older Adults with Chronic Musculoskeletal Pain: Mediating Roles of Pain Resilience and Pain Catastrophizing.

Purpose: To explore the relationship between pain intensity, pain resilience, pain catastrophizing, and pain-related activity patterns in older adults with chronic musculoskeletal pain (CMP). Patients and Methods: A total of 220 elderly Chinese with chronic musculoskeletal pain were recruited from a tertiary general hospital. Participants completed several measures including a demographic questionnaire, Brief Pain Inventory (BPI), Pain Resilience Scale (PRS), Pain Catastrophizing Scale (PCS), and Patterns of Activity Measure-Pain (POAM-P). Moreover, Process version 3.5 plug-in SPSS26 was used to test the mediation effect between variables. Results: The scores of POAM-P in older adults with CMP from high to low were: avoidance (27.39 ± 8.10), pacing (24.25 ± 9.48), and overdoing (16.65 ± 10.95). Mediation analysis revealed that pain resilience and pain catastrophizing mediated the relationship between pain intensity and pain-related activity patterns (avoidance and pacing) in older adults with CMP. Conclusion: These results provide evidence for the role of pain resilience and pain catastrophizing in the relationship between pain intensity and pain-related activity patterns. Interventions targeting these factors should be included in activity management programs for elderly CMP patients. It may be possible to reduce the negative impact of pain intensity on activity patterns by improving pain resilience and reducing pain catastrophizing.

Effect of atropine 0.01% on myopia control in children aged 6-13 years during the 2022 lockdown in Shanghai.

Purpose: To compare the myopic progression in children treated with 0. 01% atropine and those who discontinued atropine during the 2022-home quarantine in Shanghai. Methods: In this retrospective study, children aged 6-13 years with follow-up visits before (between January 2022 and February 2022) and after the lockdown (between July 2022 and August 2022) were included. Cycloplegic refraction and axial length (AL) were measured at both visits. The atropine group had continuous medication during the lockdown while the control group discontinued. The 0.01% atropine eyedrops were administered daily before bedtime. The types of spectacle lens were recorded: single vision (SV) spectacles or defocus incorporated multiple segments lenses (DIMS). Results: In total, 41 children (81 eyes) in the atropine group and 32 children (64 eyes) in the control group were enrolled. No significant difference was found in the demographic characteristics, spherical diopter, spherical equivalent (SE), AL, and follow-up time between the two groups before the lockdown in 2022 (all p > 0.1). After the home confinement, a greater myopia progression was observed in the control group (-0.46 ± 0.42 D) compared to atropine group (-0.26 ± 0.37 D; p = 0.0023). Axial elongation was also longer in the control group than that in children sustained with atropine (0.21 ± 0.17 vs. 0.13 ± 0.15 mm, p = 0.0035). Moreover, there was no significant change of spherical diopter and SE during lockdown in the atropine + DIMS combined subgroup (0.03 ± 0.033 D for spherical diopter, p = 0.7261 and 0.08 ± 0.27 D for SE, p = 0.2042, respectively). However, significant myopic shift was observed in the atropine + SV subgroup during the quarantine time (-0.31 ± 0.39 D for SE and 0.15 ± 0.16 mm for AL, both p < 0.001). Conclusion: Children treated with 0.01% atropine had slower myopia progression during the lockdown period in Shanghai compared with children discontinued. Moreover, the effect of atropine on myopic prevention can be strengthened with DIMS lenses.

Structural and biochemical basis of Arabidopsis FERONIA receptor kinase-mediated early signaling initiation.

Accumulating evidence indicates that early and essential events for receptor-like kinase (RLK) function involve both autophosphorylation and substrate phosphorylation. However, the structural and biochemical basis for these events is largely unclear. Here, we used RLK FERONIA (FER) as a model and crystallized its core kinase domain (FER-KD) and two FER-KD mutants (K565R, S525A) in complexes with ATP/ADP and Mg2+ in the unphosphorylated state. Unphosphorylated FER-KD was found to adopt an unexpected active conformation in its crystal structure. Moreover, unphosphorylated FER-KD mutants with reduced (S525A) or no catalytic activity (K565R) also adopt similar active conformations. Biochemical studies revealed that FER-KD is a dual-specificity kinase, and its autophosphorylation is accomplished via an intermolecular mechanism. Further investigations confirmed that initiating substrate phosphorylation requires autophosphorylation of the activation segment on T696, S701, and Y704. This study reveals the structural and biochemical basis for the activation and regulatory mechanism of FER, providing a paradigm for the early steps in RLK signaling initiation.

Characterisation and sequencing of the novel phage Abp95, which is effective against multi-genotypes of carbapenem-resistant Acinetobacter baumannii.

Acinetobacter baumannii has become one of the most challenging conditional pathogens in health facilities. It causes various infectious diseases in humans, such as wound or urinary tract infections and pneumonia. Phage therapy has been used as an alternative strategy for antibiotic-resistant A. baumannii infections and has been approved by several governments. Previously, we have reported two potential phage therapy candidates, Abp1 and Abp9, both of which are narrow-host-range phages. In the present study, we screened and isolated 22 A. baumannii bacteriophages from hospital sewage water and determined that Abp95 has a wide host range (29%; 58/200). The biological and genomic characteristics and anti-infection potential of Abp95 were also investigated. Abp95 belongs to the Myoviridae family, with a G+C content of 37.85% and a genome size of 43,176 bp. Its genome encodes 77 putative genes, none of which are virulence, lysogeny, or antibiotic resistance genes. Abp95 was found to accelerate wound healing in a diabetic mouse wound infection model by clearing local infections of multidrug-resistant A. baumannii. In conclusion, the lytic phage Abp95, which has a wide host range, demonstrates potential as a candidate for phage therapy against multiple sequence types of carbapenem-resistant A. baumannii.

Tissue-resident immune cells in the pathogenesis of multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) in which genetic and environmental factors contribute to disease progression. Both innate and adaptive immune cells, including T cells, B cells, activated macrophages and microglia, have been identified to be involved in the pathogenesis of MS, leading to the CNS inflammation, neurodegeneration and demyelination. In recent years, there has been considerable progress in understanding the contribution of tissue-resident immune cells in the pathogenesis of MS. METHODS: We performed a keyword-based search in PubMed database. We combined "multiple sclerosis" with keywords, such as tissue-resident memory T cells, microglia to search for relevant literatures in PubMed. RESULTS AND CONCLUSION: In this review, we comprehensively describe the characteristics of tissue-resident memory T cells and microglia, summarize their role in the pathogenesis of MS, and discuss their interaction with other immune cells in the CNS.