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Abstract Room-temperature elastocaloric cooling is considered as a zero-global-warming-potential alternative to conventional vapor-compression refrigeration technology. However, the limited entropy and large-deformation features of elastocaloric polymers hinder the creation of the breakthrough in their caloric responses and device development. Herein, we report that the addition of a small amount of inorganic nanofillers into the polymer induces the aggregate of the effective elastic chains via shearing the interlaminar molecular chains, which provides an additional contribution to the entropy in elastocaloric polymers. Consequently, the adiabatic temperature change of −18.0 K and the isothermal entropy change of 187.4 J kg−1 K−1 achieved in the polymer nanocomposites outperform those of current elastocaloric polymers. Moreover, a large-deformation cooling system with a work recovery efficiency of 56.3% is demonstrated. This work opens a new avenue for the development of high-performance elastocaloric polymers and prototypes for solid-state cooling applications.

We identified a novel ceftazidime/avibactam (CAZ/AVI) resistance mechanism in endemic sequence type 11 hypervirulent and carbapenem-resistant Klebsiella pneumoniae isolated from a patient who had not been exposed CAZ/AVI. Overexpression of blaSHV-12 caused by tandem gene amplification contributed to CAZ/AVI resistance instead of the carriage of blaKPC-2. Enhanced genomic surveillance is essential to identify emerging variants.

BackgroundNeutrophil plays a pivotal role in the management of Klebsiella pneumoniae infection. Delineate the clinical characteristics and prognostic utility of neutrophil in severe patients with K. pneumoniae infection are crucial for clinical management and prognostic assessment.MethodsK. pneumoniae patients with different infection sites were enrolled from Medical Information Mart for Intensive Care IV and eICU Collaborative Research Database. Temporal variations of neutrophil counts within 30 days of clinical onset were examined using locally weighted scatterplot smoothing curves. Logistic regression analysis was performed to assess the relationship between neutrophil counts and hospital mortality.ResultsA total of 1,705 patients caused by K. pneumonia were included in the study. The non-survivor group exhibited a comparatively older age and a higher proportion of K. pneumoniae infections originating from respiratory and bloodstream sources compared to the survivor group (38.4% vs 21.1%, p

Abstract Background The occurrence of multidrug-resistant and hypervirulent Klebsiella pneumoniae (MDR-hvKp) worldwide poses a great challenge for public health. Few studies have focused on ST218 MDR-hvKp. Methods Retrospective genomic surveillance was conducted at the Peking University Third Hospital from 2017 and clinical information was obtained. To understand genomic and microbiological characteristics, antimicrobial susceptibility testing, plasmid conjugation and stability, biofilm formation, serum killing, growth curves and whole-genome sequencing were performed. We also assessed the clinical and microbiological characteristics of ST218 compared with ST23. Results A total of eleven ST218 Kp isolates were included. The most common infection type was lower respiratory tract infection (72.7%, 8/11) in our hospital, whereas ST23 hvKp (72.7%, 8/11) was closely associated with bloodstream infection. Notably, nosocomial infections caused by ST218 (54.5%, 6/11) was slightly higher than ST23 (36.4%, 4/11). All of the ST218 and ST23 strains presented with the virulence genes combination of iucA + iroB + peg344 + rmpA + rmpA2. Interestingly, the virulence score of ST218 was lower than ST23, whereas one ST218 strain (pPEKP3107) exhibited resistance to carbapenems, cephalosporins, β-lactamase/inhibitors and quinolones and harbored an ~ 59-kb IncN type MDR plasmid carrying resistance genes including bla NDM-1, dfrA14 and qnrS1. Importantly, bla NDM-1 and qnrS1 were flanked with IS26 located within the plasmid that could successfully transfer into E. coli J53. Additionally, PEKP2044 harbored an ~ 41-kb resistance plasmid located within tetA indicating resistance to doxycycline. Conclusion The emergence of bla NDM-1 revealed that there is great potential for ST218 Kp to become a high-risk clone for MDR-hvKp, indicating the urgent need for enhanced genomic surveillance.

The fluid‐transportation functions based on the volume‐regulating behavior of the chamber‐like organs inspire the development of artificial organs. Due to the intrinsic compliance of soft robotics for biomimicking purposes and the volume‐regulation capability of the 3D origami patterns, the soft robots with origami patterns show promising potential in such research. However, the folding deformation of the origami facets cannot be straightforwardly implemented as the actuation or the body movement, and the predetermined movements of the pattern limit the appropriate functions for specific applications. In this work, an origami‐patterned rigidification (OPR) method is proposed for applying rigid origami mechanisms (herein, the cuboctahedron origami ball) to the chamber‐like structure of soft robots. The motion of the soft robot is programmed by purposefully rigidified the soft chamber following the pattern. The resultant OPR structures are granted with functions corresponding to the predetermined motion of the pattern, and the expanded movements through the bifurcation brought by the soft–rigid characteristics. The concept, design, and fabrication of the OPR robot are presented. By analyzing the deformation of the soft creases, the kinematic models of the predetermined and expanded degrees of freedom are presented and verified by experiments. The extended functions of two OPR robots are demonstrated.

Abstract The identification of effective drug targets and the development of bioactive molecules are areas of high need in cancer therapy. The phosphatidylinositol transfer protein alpha/beta isoform (PITPα/β) has been reported to play an essential role in integrating phosphoinositide trafficking and lipid metabolism in diverse cellular processes but remains unexplored as a potential target for cancer treatment. Herein, data analysis of clinical cancer samples revealed that PITPα/β expression is closely correlated with the poor prognosis. Target identification by chemical proteomic methods revealed that microcolin H, a naturally occurring marine lipopeptide, directly binds PITPα/β and displays antiproliferative activity on different types of tumour cell lines. Furthermore, we identified that microcolin H treatment increased the conversion of LC3I to LC3II, accompanied by a reduction of the level of p62 in cancer cells, leading to autophagic cell death. Moreover, microcolin H showed preeminent antitumour efficacy in nude mouse subcutaneous tumour models with low toxicity. Our discoveries revealed that by targeting PITPα/β, microcolin H induced autophagic cell death in tumours with efficient anti-proliferating activity, which sheds light on PITPα/β as a promising therapeutic target for cancer treatment.

Abstract Earthworms have entirely soft bodies mainly composed of circular and longitudinal muscle bundles but can handle the complexity of unstructured environments with exceptional multifunctionality. Soft robots are naturally appropriate for mimicking soft animal structures thanks to their inherent compliance. Here, we explore the new possibility of using this compliance to coordinate the actuation movements of single-type soft actuators for not only high adaptability but the simultaneous multifunctionality of soft robots. A cross-linked actuator coordination mechanism is proposed and explained with a novel conceptual design of a cross-linked network, characterization of modular coordinated kinematics, and a modular control strategy for multiple functions. We model and analyze the motion patterns for these functions, including grabbing, manipulation, and locomotion. This further enables the combination of simultaneous multi-functions with this very simple actuator network structure. In this way, a soft modular robot is developed with demonstrations of a novel continuous-transportation mode, for which multiple objects could be simultaneously transported in unstructured environments with either mobile manipulation or pick-and-place operation. A comprehensive workflow is presented to elaborate the cross-linked actuator coordination concept, analytical modeling, modular control strategy, experimental validation, and multi-functional applications. Our understanding of actuator coordination inspires new soft robotic designs for wider robotic applications.

Background: The rate of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has been increasing rapidly worldwide and, poses a significant risk to human health. Effective methods are urgently needed to address treatment failures related to antibiotic resistance. Recent research has reported that some drugs in combination with antibiotics have displayed synergistic killing of resistant bacteria. Here, we investigated whether glutathione (GSH) can synergize with meropenem, and enhance its effectiveness against CRKP.Methods: Synergistic activity was assessed by checkerboard and time-killing assays. The mechanism of these combinations was assessed by total ROS and membrane permeability assays. The bacterial metabolites were assessed by LC‒MS/MS.Results: The FICIs of GSH and meropenem were approximately 0.5 and the combined treatment with GSH and meropenem resulted in a more than 2log10 CFU/mL reduction in bacteria compared to the individual treatments. These findings indicated the synergistic effect of the two drugs. Moreover, the meropenem MIC of CRKP was reduced to less than 4 mg/L when combined with 6 mg/mL GSH, indicating that GSH could significantly reverse resistance to meropenem in bacteria. The production of ROS in bacteria was determined by flow cytometry. After adding GSH, the ROS in the GSH group and the combined group was significantly higher than that in the control and meropenem groups, but there was no significant difference between the combined and GSH groups. The metabolic disturbance caused by GSH alone and in combination with meropenem was significant intracellularly and extracellularly, especially in terms of glycerophospholipid metabolism, indicating that the synergistic effect of the combined use of GSH and meropenem was relevant to glycerophospholipid metabolism. In addition, we measured the cell membrane permeability. The cell membrane permeability of the combination group was significantly higher than that of the blank control or monotreatment groups. This confirmed that the GSH can serve as a meropenem enhancers by disturbing glycerophospholipid metabolism and increasing cell membrane permeability.Conclusion: GSH and meropenem display a synergistic effect, wherein GSH increases the sensitivity of CRKP to meropenem. The synergy and susceptibility effects are thought to related to the increased membrane permeability resulting from the perturbations in glycerophospholipid metabolism, presenting a novel avenue for CRKP treatment.

In order to improve the thermal stability of PCD during practical application, the mixed solution of sulfuric acid and hydrogen peroxide was selected to remove cobalt from PCD. The effect of decobaltization on microstructure and mechanical property of PCD as well as its mechanism were studied. According to the SEM results, several deep corrosion pits were observed on the surface of PCD after the 48 h decobaltization process under room temperature, indicating that the cobalt phase was almost removed. Besides, the depths of decobaltization on the upper and lower surfaces were 176 μm and 162 μm, respectively. Based on the EDS results, the remaining mass fraction of cobalt in the decobaltized layer was determined to be 0.93%, while that in the non-decobaltized layer was 7.64%. This suggested that 87.83% of cobalt was dissolved and removed in the mixed solution of sulfuric acid and hydrogen peroxide. The residual stress of PCD samples was also measured. The residual stress before and after decobaltization was 483.91 MPa and 330.35 MPa, respectively. The reduction of 31.73% indicated that decobaltization could effectively reduce the residual thermal stress in PCD.

Abstract Objectives ST11 KPC-producing Klebsiella pneumoniae (Kp) is highly prevalent in China. We investigated the inter- and intra- host transmission and evolution characteristics of ST11 KPC-producing Kp. Methods A retrospective study was conducted in a hospital. The clinical data and antimicrobial resistance (AMR) phenotypes were collected. Whole genome sequencing was performed. The transmission route was reconstructed by combining single nucleotide polymorphisms (SNPs) with the clinical information. Hypervirulent Kp (HvKp) was defined as the presence of some combination of peg-344, iroB, iucA, rmpA, or rmpA2. Results Fifty-eight Kp strains isolated from thirty-five patients were enrolled. The information of one isolate was missing. The mean age of the patients was 74.3 ± 18.0 years, and 18 (50.0%) were female. Fifteen patients (41.7%, 15/36) presented with poor prognosis. All the strains were identified as ST11, and 57 strains harbored bla KPC-2. Two distinguished clades were identified based on the 1,325 high quality SNPs. In clade 1, carbapenem-resistant (CR)-hvKp accounted for 48.3% of the strains (28/58), which mostly presented as KL64 subclones, whereas CR-classical Klebsiella pneumoniae (cKp) commonly possessing KL47 were clustered in Clade 2. One CR-hvKp strain might have originated from the CR-cKp strain from within-host evolution. Even worse, a prolonged transmission of CR-hvKp has led to its spread into healthcare institutes. Conclusion Two endemic subclones of ST11 KPC-producing Kp, KL64-CR-hvKp and KL47-CR-cKp, were transmitted in parallel within the hospital and/or the healthcare institute, suggesting that the ongoing genomic surveillance should be enhanced.

ObjectivesThis study aimed to compare the burden and trends of stroke attributed to dietary risk factors in the Belt and Road (“B&R”) countries from 1990 to 2019.MethodsThe 2019 Global Burden of Disease (GBD) Study was used to gather information on the burden of stroke attributable to dietary risk factors. Numbers and age-standardized rates (ASRs) of deaths, disability-adjusted life years (DALYs) were determined in 1990 and 2019 among the “B&R” countries. The average annual percent change (AAPC) was used to analyze the temporal trends of diet-induced stroke DALYs from 1990 to 2019 and in the final decade (2010–2019) by Joinpoint regression analysis.ResultsIn 2019, the absolute number of stroke deaths and DALYs attributable to dietary risk factors were 671,872 cases (95% UI 436,354–937,093) and 1.67 million cases (95% UI 1.15–2.24) in China. We found geographical differences in mortality and DALYs of diet-attributable stroke among member countries, with Bulgaria, Hungary and Serbia being the three highest countries in 1990, Bulgaria, North Macedonia and Montenegro in Central Asia in 2019. The ASRs of diet-induced stroke mortality and DALYs were generally declining in most member states from 1990 to 2019, however, the corresponding metrics in Mongolia remained high. The fastest decline in ASR of mortality and DALYs for diet-induced stroke was seen in Estonia, Eastern Europe, with AAPC values of −7.09% (95%CI: −7.72, −6.46%) and − 6.62% (95%CI: −7.20, −6.03%), respectively. We noted a substantial downward trend in ASR of mortality and DALYs from diet-induced stroke changes in the final decade (2010–2019) for most member states. The ASR of DALYs for diet-induced stroke decreased greater in females than in males. For those aged 50–74, the DALYs for stroke due to dietary risk factors in all other member countries of the “B&R” showed a decreasing trend, except for the Philippines, which rose (AAPC = 2.13, 95%CI: 1.40–2.87%) and Turkmenistan, which remained stable (AAPC = 0.05, 95%CI: −0.43–0.33%).ConclusionThe burden of diet-induced stroke varies substantially across “B&R” countries and threaten public health, relevant evidence-based policies and interventions should be adopted to address the future burden of stroke in “B&R” countries through extensive collaboration.

Trunk-like continuum robots have wide applications in manipulation and locomotion. In particular, trunk-like soft arms exhibit high dexterity and adaptability very similar to the creatures of the natural world. However, owing to the continuum and soft bodies, their performance in payload and spatial movements is limited. In this paper, we investigate the influence of key design parameters on robotic performance. It is verified that a larger workspace, lateral stiffness, payload, and bending moment could be achieved with adjustments to soft materials’ hardness, the height of module segments, and arrayed radius of actuators. Especially, a 55% increase in arrayed radius would enhance the lateral stiffness by 25% and a bending moment by 55%. An 80% increase in segment height would enlarge 112% of the elongation range and 70 % of the bending range. Around 200% and 150% increments in the segment’s lateral stiffness and payload forces, respectively, could be obtained by tuning the hardness of soft materials. These relations enable the design customization of trunk-like soft arms, in which this tapering structure ensures stability via the stocky base for an impact reduction of 50% compared to that of the tip and ensures dexterity of the long tip for a relatively larger bending range of over 400% compared to that of the base. The complete methodology of the design concept, analytical models, simulation, and experiments is developed to offer comprehensive guidelines for trunk-like soft robotic design and enable high performance in robotic manipulation.

Exploring the effective recycling of waste styrene-butadiene-styrene block copolymer (SBS) modified asphalt mixture is the difficulty and hotspot in the field of road materials research. Common rejuvenation method and reactive rejuvenation method were used to recover the road performances of aged SBS modified asphalt mixture (ASMBM) in this paper. The recovery effect of high- and low-temperature performance, fatigue resistance and water stability for ASMBM after rejuvenation was studied, and the road performance development of ASMBM after reactive rejuvenation in the early stage was also investigated. The results show that reactive rejuvenation method could significantly enhance the Marshall stability and rutting resistance of rejuvenated ASMBM, and further improve its low-temperature cracking resistance as compared with common rejuvenation method, which attributes to the reconstruction of aged SBS cross-linking structure and its improvement on the interface stability of rejuvenated mixture. Meanwhile, the fatigue life of reactive rejuvenated ASMBM under strain level of 400 με is 26.6 % higher than that of common rejuvenated mixture. Water stability test results show that reactive rejuvenation is more beneficial to restore the water-immersed Marshall stability and Hamburger rutting resistance of ASMBM. Furthermore, the road performances of reactive rejuvenated ASMBM have a further improvement with the extension of time in the early stage after rejuvenation, its Marshall stability, the freeze-thaw splitting strength ratio and water-immersed Marshall stability could restore to the initial level of fresh mixture. Thus, reactive rejuvenation method is more conducive to realizing the high-performance recycling of waste SBS modified asphalt mixture and enhance its recycling value.

Parkin is a well-established synergistic mediator of mitophagy in dysfunctional mitochondria. Mitochondria are the main target of arsenic trioxide (ATO) cytotoxicity, and the effect of mitophagy on ATO action remains unclear. In this study, we used stable Parkin-expressing (YFP-Parkin) and Parkin loss-of-function mutant (Parkin C431S) HeLa cell models to ascertain whether Parkin-mediated mitophagy participates in ATO-induced apoptosis/cell death. Our data showed that the overexpression of Parkin significantly sensitized HeLa cells to ATO-initiated proliferation inhibition and apoptosis; however, the mutation of Parkin C431S significantly weakened this Parkin-mediated responsiveness. Our further investigation found that ATO significantly downregulated two fusion proteins (Mfn1/2) and upregulated fission-related protein (Drp1). Autophagy was also activated as evidenced by the formation of autophagic vacuoles and mitophagosomes, increased expression of PINK1, and recruitment of Parkin to impaired mitochondria followed by their degradation, accompanied by the increased transformation of LC3-I to LC3-II, increased expression of Beclin1 and decreased expression of P62 in YFP-Parkin HeLa cells. Enhanced mitochondrial fragmentation and autophagy indicated that mitophagy was activated. Furthermore, during the process of mitophagy, the overproduction of ROS implied that ROS might represent a key factor that initiates mitophagy following Parkin recruitment to mitochondria. In conclusion, our findings indicate that Parkin is critically involved in ATO-triggered mitophagy and functions as a potential antiproliferative target in cancer cells.

Abstract Cadmium (Cd) contamination in water and soil is considered an environmental pollutant. Food crops can absorb and accumulate bioavailable Cd. Continuous monitoring of Cd levels in the environment can minimize exposure and harm to humans. Visual pigments have been demonstrated to have great potential in the development of minimal-equipment biosensors. In the present study, a metabolically engineered bacterium was employed to produce blue-purple pigment violacein responsive to toxic Cd(II). The high stability of the bisindole pigment contributed to determining the violacein at wavelengths of 578 nm. Visual and quantifiable signals could be captured after a 1.5-h Cd(II) exposure. This novel biosensor showed significantly stronger responses to Cd(II) than to other heavy metals including Pb(II), Zn(II), and Hg(II). A significant increase in pigment signal was found to respond to as low as 0.049 μM Cd(II). The naked eye can detect the color change when violacein-based biosensor is exposed to 25 μM Cd(II). A high-throughput method for rapid determination of soluble Cd(II) in environmental water was developed using a colorimetric microplate.

In the published publication [...]

ABSTRACT Multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-hvKp) has been emerging worldwide. However, the clinical, microbiological, and genomic characteristics of newly emerged MDR sequence type 65 (ST65) hvKp are unclear. We conducted active longitudinal genomic surveillance of K. pneumoniae in the hospital starting in 2017. Clinical characteristics, including demographic data, infection type, and outcomes, were collected. Whole-genome sequencing was performed to clarify phylogenetic and plasmid features, and phenotype determined by growth curves, plasmid transferability and stability, hypermucoviscosity, biofilm formation, and serum survival were analyzed to microbiologically characterize ST65 in depth. Ten ST65 (1.4%, 10/720) isolates were detected from 720 K. pneumoniae isolates in total. Nine patients (90%, 9/10) were older than 60 years and had multiple underlying diseases. All ST65 K. pneumoniae isolates harbored iucA, rmpA, rmpA2, iroB, and peg344 and were identified as hvKp. Surprisingly, two MDR-hvKp isolates that grew slowly were observed. Isolate PEKP4222 harbored a pLVPK-like plasmid and a conjunctive MDR plasmid. Isolate P1 harbored blaKPC-3 in a new plasmid, pP1-54, resulting in an extensively drug-resistant (XDR) phenotype; this isolate, which might have evolved from a strain harboring blaKPC-2, resulted in fatal infection. The pP1-54 plasmid could not be transferred to Escherichia coli by conjugation but could be stably inherited vertically. Interestingly, P1 also carried the pLVPK-like plasmid and acquired various antimicrobial resistance genes, and blaCTX-M-3 was detected in the IncB/O/K/Z plasmid. The convergence of XDR and hypervirulence within classical ST65 hvKp is emerging, highlighting the need for enhanced genomic surveillance. IMPORTANCE XDR-hvKp poses a great challenge to public health. ST65, a classical hvKp subtype, mostly presented with hypermucoviscosity, which restricts antimicrobial resistance acquisition. However, few studies have demonstrated the clinical, microbiological, and genomic characteristics of ST65, especially MDR-ST65 hvKp. Here, we first reported that ST65 hvKp acquired blaKPC-3 and then conferred the XDR-hvKp phenotype. Genomic context analysis concluded that the blaKPC-3 gene might have evolved from blaKPC-2. Additionally, the pLVPK-like plasmid seemed to acquire more resistance genes, and blaCTX-M-3 located in the IncB/O/K/Z plasmid was observed. The XDR-hvKp phenotype could be stably inherited vertically, indicating that strains harboring blaKPC-3 and pLVPK-like plasmids could persistently exist in hospital settings. These data suggest that genomic adaptation is rapid and that enhanced surveillance is essential.

Although arsenic trioxide (ATO) shows a strong anti-tumor effect in the treatment of acute promyelocytic leukemia, it does not benefit patients with hepatocellular carcinoma (HCC). Thus, combination therapy is proposed to enhance the efficacy of ATO. Parthenolide (PTL), a natural compound, selectively eradicates cancer cells and cancer stem cells with no toxicity to normal cells. In this study, we chose PTL and ATO in combination and found that nontoxic dosage of PTL and ATO co-treatment can synergistically inhibit the in vitro and in vivo proliferation activity of HCC cells through suppressing stemness and self-renewal ability and inducing mitochondria-dependent apoptosis. More importantly, USP7-HUWE1-p53 pathway is involved in PTL enhancing ATO-induced apoptosis of HCC cell lines. Meanwhile, accompanied by induction of apoptosis, PTL and ATO evoke autophagic activity via inhibiting PI3K/Akt/mTOR pathway, and consciously controlling autophagy can improve the anti-HCC efficacy of a combination of PTL and ATO. In short, our conclusion represents a novel promising approach to the treatment of HCC.

AbstractThis study is aimed at exploring the mechanical properties and failure characteristics of the rocks surrounding a railway tunnel in Qinghai-Tibet Plateau at typical buried depths. Uniaxial compression and AE experiments were carried out on sandstones taken from the same borehole. The results show that the elastic modulus and peak strength of the 750 m depth sandstones are much higher than those of the 350 m depth sandstones. The crack evolution in the 750 m depth sandstones was more orderly, and its brittle failure characteristics were more obvious as compared with the 350 m depth sandstones. The fractal dimension of the samples from the typical depths reached the minimum value when the fracture volume state changed from compression to expansion. In addition, the damage variable based on the crack volumetric strain theory (DC) and cumulative ring counts of acoustic emission (DA) can, respectively, reflect the generation and penetration of cracks and the physical properties of rocks at the two typical depths. The combination of DC and DA can be used to analyze the evolution of the sandstone’s damage. The research results have basic theoretical significance for the excavation and geological disaster prevention of tunnels in sandstone sections at typical depths in the Qinghai-Tibet Plateau.

Helicobacter pylori (H. pylori)-derived vacuolating cytotoxin A (VacA) causes damage to various organelles, including mitochondria, and induces autophagy and cell death. However, it is unknown whether VacA-induced mitochondrial damage can develop into mitophagy. In this study, we found that H. pylori, H. pylori culture filtrate (HPCF), and VacA could activate autophagy in a gastric epithelial cell line (GES-1). VacA-caused mitochondrial depolarization retards the import of PINK1 into the damaged mitochondria and evokes mitophagy. And, among mass spectrometry (LC-MS/MS) identified 25 mitochondrial proteins bound with VacA, Tom20, Tom40, and Tom70, TOM complexes responsible for PINK1 import, were further identified as having the ability to bind VacA in vitro using pull-down assay, co-immunoprecipitation, and protein–protein docking. Additionally, we found that the cell membrane protein STOM and the mitochondrial inner membrane protein PGAM5 also interacted with VacA. These findings suggest that VacA captured by STOM forms endosomes to enter cells and target mitochondria. Then, VacA is transported into the mitochondrial membrane space through the TOM complexes, and PGAM5 aids in inserting VacA into the inner mitochondrial membrane to destroy the membrane potential, which promotes PINK1 accumulation and Parkin recruitment to induce mitophagy. This study helps us understand VacA entering mitochondria to induce the mitophagy process.

Background and purpose: Multiple proinflammatory cytokines in tumorigenic microenvironment are involved in the acquired capability for invasive growth and metastasis. It is not clear whether protein kinase CβⅡ(PKCβⅡ) can modulate the secretion of proinflammatory cytokines to promote the progression of hepatocellular carcinoma (HCC). This study aimed to explore the function and mechanism of PKCβⅡ in the invasion of HCC to investigate the relationship between PKCβⅡ and tumor inflammatory microenvironment. Methods: The effect of conditioned medium from PKCβⅡ-overexpressing cells on the invasion of HCC cells was detected by the transwell assay. Serum-free culture supernatants were analyzed by cytokine arrays. The effect of PKCβⅡ overexpression on the expression of interleukin-6 (IL-6) in supernatants and at mRNA level was examined by enzyme- linked immunosorbent assay (ELISA) and real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) respectively. The effects of IL-6 neutralizing antibody and IL-6 receptor (IL-6R) neutralizing antibody on PKCβⅡ overexpression-induced invasion of HCC cells were detected by the transwell assay. The expressions of signal transducer and activator of transcription 3 (STAT3) and P-STAT3 were detected by Western blot. Correlation of PKCβⅡ with the expression of IL-6 in clinical HCC cases was analyzed using the nonparametric Spearman test. Results: Conditioned medium obtained from PKCβⅡ-overexpressing cells significantly induced the invasiveness of Huh7 (P

ObjectiveThe impact of the mindfulness-based stress reduction (MBSR) program on psychological outcomes and quality of life (QoL) in lung cancer patients remains unclear. This meta-analysis aimed to evaluate the effectiveness of the MBSR program on psychological states and QoL in lung cancer patients.MethodsEligible studies published before November 2021 were systematically searched from PubMed, EMBASE, Cochrane Library, PsycINFO, China National Knowledge Infrastructure (CNKI), and Wanfang databases. The risk of bias in eligible studies was assessed using the Cochrane tool. Psychological variables and QoL were evaluated as outcomes. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to grade the levels of evidence. Statistical analysis was conducted using RevMan 5.4 and STATA 14.0.ResultsA total of 17 studies involving 1,680 patients were included for meta-analysis eventually. MBSR program significantly relieved cancer-related fatigue (standard mean difference [SMD], −1.26; 95% confidence interval [CI], −1.69 to −0.82; moderate evidence) and negative psychological states (SMD, −1.35; 95% CI, −1.69 to −1.02; low evidence), enhanced positive psychological states (SMD, 0.91; 95% CI, 0.56–1.27; moderate evidence), and improved quality of sleep (MD, −2.79; 95% CI, −3.03 to −2.56; high evidence). Evidence on MBSR programs' overall treatment effect for QoL revealed a trend toward statistical significance (p = 0.06, low evidence).ConclusionBased on our findings, the MBSR program shows positive effects on psychological states in lung cancer patients. This approach should be recommended as a part of the rehabilitation program for lung cancer patients.Systematic Review Registrationhttps://archive.org/details/osf-registrations-mwvbq-v1, identifier: 10.17605/OSF.IO/MWVBQ.

AimsA negative association between the lower level of psychological resilience (PR) and increased risk of compassion fatigue (CF) and higher Coronavirus disease 2019 (COVID-19) stress has been revealed. However, bibliometric studies have not been performed to comprehensively investigate this topic. This study aimed to identify the status and trends in the CF and PR field from 2008 to 2021 and during the COVID-19 pandemic.MethodsWe identified relevant literature from the Web of Science Core Collection® database using “resilience” and “compassion fatigue” on September 30, 2021. All search results were exported in plain text format for collaboration network analysis, reference-based co-citation analysis, analysis of journals, and keywords-based co-occurrence analysis, which were performed using Citespace® 5.8.R1.ResultsA total of 388 publications were identified finally, and there has been an increasing trend in the annual number of publications with light fluctuations. The analysis of journals and keywords indicated that nurses and social workers are the main research targets, and their mental problems are the main research topics. The turnover intention of health care providers has been a research focus, particularly during the COVID-19.ConclusionThe results of the present study help us understand the status of the CF and PR field and its recent developments.

BackgroundSequence type 11 (ST11) Klebsiella pneumoniae (Kp) is highly prevalent in China and is a typical sequence type among KPC-producing isolates. This study aimed to evaluate the clinical outcomes and microbiological features of ST11 Kp infections.MethodsA retrospective cohort study was conducted at Peking University Third Hospital from January 2017 to March 2021. Clinical data were collected from medical records. Antimicrobial susceptibility testing and string tests were performed. Whole-genome sequencing was used to analyze the capsular serotypes, detect virulence-associated genes, and perform multilocus sequence typing. The risk of all-cause mortality in ST11 Kp-infected patients was compared to that in non-ST11 Kp-infected patients.ResultsFrom 139 patients infected with Kp, 49 ST11 Kp (35.3%) strains were isolated. The Charlson comorbidity index in the ST11 group was higher than that in the non-ST11 group (3.94 ± 1.59 vs. 2.41 ± 1.54, P = 0.001). A greater number of ST11 Kp-infected patients required ICU admission (46.9 vs. 16.7%, P < 0.001) and mechanical ventilation (28.6 vs. 10.0%, P = 0.005). All ST11 isolates presented a multidrug-resistant (MDR) phenotype, and twenty-nine (59.2%) hypervirulent Kp (hvKp) were identified. Twenty-four ST11 strains presented with hypermucoviscosity. The presence of capsular types K47 and K64 was frequent in the ST11 Kp strains (P < 0.001). The key virulence-associated genes rmpA, rmpA2, iucA, iroB, and peg344 were present in 26.5, 42.9, 59.2, 0, and 26.5% of the isolates, respectively, in the ST11 group. Twenty-one ST11 isolates harbored the combination of iucA+rmpA2. The 30-day mortality rate and sequential organ failure assessment (SOFA) score were significantly higher in ST11 Kp-infected patients than in non-ST11 Kp-infected patients (P < 0.01). ST11 Kp infection appeared to be an independent risk factor for mortality in ST11 Kp-infected patients.ConclusionsA high prevalence of the ST11 clone was found in the hospital, which accounted for elevated antimicrobial resistance and exhibited great molecularly inferred virulence. Patients with ST11 Kp infection had a tendency toward increased 30-day mortality and SOFA scores. ST11 Kp infection was an independent risk factor for mortality, suggesting that enhanced surveillance and management are essential.

Genetically programmed biosensors have been widely used to monitor bioavailable heavy metal pollutions in terms of their toxicity to living organisms. Most bacterial biosensors were initially designed to detect specific heavy metals such as mercury and cadmium. However, most available biosensors failed to distinguish cadmium from various heavy metals, especially mercury. Integrating diverse sensing elements into a single genetic construct or a single host strain has been demonstrated to quantify several heavy metals simultaneously. In this study, a dual-sensing construct was assembled by employing mercury-responsive regulator (MerR) and cadmium-responsive regulator (CadR) as the separate sensory elements and enhanced fluorescent protein (eGFP) and mCherry red fluorescent protein (mCherry) as the separate reporters. Compared with two corresponding single-sensing bacterial sensors, the dual-sensing bacterial sensor emitted differential double-color fluorescence upon exposure to 0–40 μM toxic Hg(II) and red fluorescence upon exposure to toxic Cd(II) below 200 μM. Bioavailable Hg(II) could be quantitatively determined using double-color fluorescence within a narrow concentration range (0–5 μM). But bioavailable Cd(II) could be quantitatively measured using red fluorescence over a wide concentration range (0–200 μM). The dual-sensing biosensor was applied to detect bioavailable Hg(II) and Cd(II) simultaneously. Significant higher red fluorescence reflected the predominant pollution of Cd(II), and significant higher green fluorescence suggested the predominant pollution of Hg(II). Our findings show that the synergistic application of various sensory modules contributes to an efficient biological device that responds to concurrent heavy metal pollutants in the environment.

PurposeThe aims of the study were first to investigate the association between illness perception and psychological distress and second to determine whether mindfulness affects psychological distress via illness perception and perceived stress in patients with lung cancer.MethodsAmong 300 patients with lung cancer who participated in this cross-sectional study, 295 patients made valid responses to distress thermometer (DT), the Five Facet Mindfulness Questionnaire (FFMQ), the Brief Illness Perception Questionnaire (B-IPQ), and the Perceived Stress Scale (PSS) between January and July 2021. The possible pathways of mindfulness affecting psychological distress were analyzed based on the structural equation modeling analysis.ResultsA total of 24.4% patients with lung cancer had DT > 4. Illness perception (β = 0.17, p = 0.002) and perceived stress (β = 0.23, p < 0.001) had a direct effect on psychological distress. Mindfulness had a direct effect on illness perception (β = −0.16, p = 0.006) and mindfulness indirectly influenced psychological distress (β = −0.04, p = 0.009) through affecting illness perception alone or simultaneously affecting both the illness perception and perceived stress in patients with lung cancer.ConclusionLung cancer suffered from varying levels of psychological distress. Mindfulness may alleviate psychological distress by reducing the level of illness perception and perceived stress. We suggest developing a comprehensive factor model to clarify potential mechanisms of mindfulness on psychological distress due to the very low effect of mindfulness on psychological distress via illness perception and perceived stress.

Objective: To investigate the efficacy and safety of narrow band intense pulsed light (DPL) combined with long pulse 1 064 nm Nd∶YAG laser for infant port wine stain. Methods: A total of 98 patients with infant port wine stain were randomly divided into two groups. The treatment group (58 cases) was treated with DPL and long pulse 1 064 nm Nd∶YAG laser for 3~5 treatment session at 4-week interval, while 40 patients treated with DPL alone served as controls. Follow-up was performed 1 month after the last treatment. Results: Combination of DPL and long pulse 1 064 nm Nd∶YAG laser displayed a total effective rate of 70.69%, including complete clearance (13 cases, 22.41%), marked improvement (16 cases, 27.58%), and some improvement (12 cases, 20.68%). In contrast, only 37.50% of patients treated with DPL alone showed improvement, including 2 cases of complete clearance (5.00%), 8 cases of marked improvement (20.00%), and 5 cases of some improvement (12.50%). Total effective rates differed significantly between the two groups (χ2=10.65, P