Cell-to-cell natural transformation in Bacillus subtilis facilitates large scale of genomic exchanges and the transfer of long continuous DNA regions.

Natural transformation is one of the major mechanisms of horizontal gene transfer. Although it is usually studied using purified DNA in the laboratory, recent studies showed that many naturally competent bacteria acquired exogenous DNA from neighboring donor cells. Our previous work indicates that cell-to-cell natural transformation (CTCNT) using two different Bacillus subtilis strains is a highly efficient process; however, the mechanism is unclear. In this study, we further characterized CTCNT and mapped the transferred DNA in the recombinants using whole genome sequencing. We found that a recombinant strain generated by CTCNT received up to 66 transferred DNA segments; the average length of acquired continuous DNA stretches was approximately 27 kb with a maximum length of 347 kb. Moreover, up to 1.54 Mb genomic DNA (37% of the chromosome) was transferred from the donors into one recipient cell. These results suggest that B. subtilis CTCNT facilitates horizontal gene transfer by increasing the transfer of DNA segments and fostering the exchange of large continuous genomic regions. This indicates that the potency of bacterial natural transformation is underestimated using traditional approaches and reveals that DNA donor cells may play an important role in the transformation process in natural environments.

A virus-borne DNA damage signaling pathway controls the lysogeny-induction switch in a group of temperate pleolipoviruses.

Many prokaryotic viruses are temperate and their reactivation is tightly regulated. However, except for a few bacterial model systems, the regulatory circuits underlying the exit from lysogeny are poorly understood, especially in archaea. Here, we report a three-gene module which regulates the switch between lysogeny and replicative cycle in a haloarchaeal virus SNJ2 (family Pleolipoviridae). The SNJ2 orf4 encodes a winged helix-turn-helix DNA binding protein which maintains lysogeny through repressing the expression of the viral integrase gene intSNJ2. To switch to the induced state, two other SNJ2-encoded proteins, Orf7 and Orf8, are required. Orf8 is a homolog of cellular AAA+ ATPase Orc1/Cdc6, which is activated upon mitomycin C-induced DNA damage, possibly through posttranslational modification. Activated Orf8 initiates the expression of Orf7 which, in turn, antagonizes the function of Orf4, leading to the transcription of intSNJ2, thereby switching SNJ2 to the induced state. Comparative genomics analysis revealed that the SNJ2-like Orc1/Cdc6-centered three-gene module is common in haloarchaeal genomes, always present in the context of integrated proviruses. Collectively, our results uncover the first DNA damage signaling pathway encoded by a temperate archaeal virus and reveal an unexpected role of the widely distributed virus-encoded Orc1/Cdc6 homologs.

Integrated Manipulation and Addressing of Spin Defect in Diamond.

Scalable and addressable integrated manipulation of qubits is crucial for practical quantum information applications. Different waveguides have been used to transport the optical and electrical driving pulses, which are usually required for qubit manipulation. However, the separated multifields may limit the compactness and efficiency of manipulation and introduce unwanted perturbation. Here, we develop a tapered fiber-nanowire-electrode hybrid structure to realize integrated optical and microwave manipulation of solid-state spins at nanoscale. Visible light and microwave driving pulses are simultaneously transported and concentrated along an Ag nanowire. Studied with spin defects in diamond, the results show that the different driving fields are aligned with high accuracy. The spatially selective spin manipulation is realized. And the frequency-scanning optically detected magnetic resonance (ODMR) of spin qubits is measured, illustrating the potential for portable quantum sensing. Our work provides a new scheme for developing compact, miniaturized quantum sensors and quantum information processing devices.

Muscular Function Recovery from General Anesthesia in 132 Patients Undergoing Surgery with Acceleromyography, Combined Acceleromyography, and Ultrasonography, and without Monitoring Muscular Function.

BACKGROUND Diaphragmatic thickness fraction (DTF), measured by ultrasound, can predict the occurrence of postoperative residual neuromuscular blockade (RNMB). We hypothesized that the utilization of diaphragmatic ultrasound during the postoperative awakening phase of anesthesia in patients offers a successful means of avoiding RNMB in a notably comfortable manner, as compared to the use of acceleromyograph. MATERIAL AND METHODS Patients who underwent elective thyroid cancer radical surgery were enrolled in this prospective clinical study. Eligible participants were randomly assigned to 1 of 3 groups: 1) combined ultrasonography with acceleromyography group (the US+AMG group), 2) the AMG group, or 3) the usual clinical practice group (the UCP group). The primary outcomes of the study were the incidence of RNMB and hypoxemia after tracheal extubation. RESULTS The study included a total of 127 patients (43 in the US+AMG group, 44 in the AMG group, and 40 in the UCP group). The incidence of RNMB and hypoxemia was higher in the UCP group than in the US+AMG and AMG groups at 15 and 30 min after extubation, respectively. The mean area under the receiver operating characteristic curve, and the decision curve of the recovery rate of DTF (DTF) was greater than that of DTF. CONCLUSIONS The use of diaphragm ultrasound during the postoperative awakening phase of anesthesia can significantly reduce the incidence of RNMB. This method was non-inferior to the use of AMG during the entire perioperative period.

Osteopontin: A Novel Therapeutic Target for Respiratory Diseases.

Osteopontin (OPN) is a multifunctional phosphorylated protein that is involved in physiological and pathological events. Emerging evidence suggests that OPN also plays a critical role in the pathogenesis of respiratory diseases. OPN can be produced and secreted by various cell types in lungs and overexpression of OPN has been found in acute lung injury/acute respiratory distress syndrome (ALI/ARDS), pulmonary hypertension (PH), pulmonary fibrosis diseases, lung cancer, lung infection, chronic obstructive pulmonary disease (COPD), and asthma. OPN exerts diverse effects on the inflammatory response, immune cell activation, fibrosis and tissue remodeling, and tumorigenesis of these respiratory diseases, and genetic and pharmacological moudulation of OPN exerts therapeutic effects in the treatment of respiratory diseases. In this review, we summarize the recent evidence of multifaceted roles and underlying mechanisms of OPN in these respiratory diseases, and targeting OPN appears to be a potential therapeutic intervention for these diseases.

Emerging Roles of Galectin-3 in Pulmonary Diseases.

Galectin-3 is a multifunctional protein that is involved in various physiological and pathological events. Emerging evidence suggests that galectin-3 also plays a critical role in the pathogenesis of pulmonary diseases. Galectin-3 can be produced and secreted by various cell types in the lungs, and the overexpression of galectin-3 has been found in acute lung injury/acute respiratory distress syndrome (ALI/ARDS), pulmonary hypertension (PH), pulmonary fibrosis diseases, lung cancer, lung infection, chronic obstructive pulmonary disease (COPD), and asthma. Galectin-3 exerts diverse effects on the inflammatory response, immune cell activation, fibrosis and tissue remodeling, and tumorigenesis in these pulmonary disorders, and genetic and pharmacologic modulation of galectin-3 has therapeutic effects on the treatment of pulmonary illnesses. In this review, we summarize the structure and function of galectin-3 and the underlying mechanisms of galectin-3 in pulmonary disease pathologies; we also discuss preclinical and clinical evidence regarding the therapeutic potential of galectin-3 inhibitors in these pulmonary disorders. Additionally, targeting galectin-3 may be a very promising therapeutic approach for the treatment of pulmonary diseases.

Expert consensus on perioperative integrated skincare for noninvasive energy-based device aesthetic procedures in clinical practice in China.

BACKGROUND: Noninvasive energy-based device (NI-EBD) aesthetic procedures has recently gained widespread usage for treating various skin conditions, enhancing skin texture and performing rejuvenation-related procedures. However, practically all NI-EBD procedures result in variable degrees of damage to the skin barrier, inducing pathological and physiological processes such as oxidative stress and inflammation, and only a small percentage of individuals possess the innate ability to restore it. OBJECTIVE: To introduce the concept of integrated skincare and establish standardized operational procedures for perioperative integrated skincare, and furnish a theoretical basis for clinical diagnosis and treatment performed by professional medical aestheticians. METHODS: The author leveraged domestic and international guidelines, clinical practice expertise and evidence-based research, adapting them to suit the specific circumstances in China. RESULTS: The consensus were provided four parts, including concept and essence of integrated skincare, integrated skincare significance during the perioperative phase of NI-EBD procedures, active ingredients and functions of effective skincare products, standardized perioperative skincare procedure for NI-EBD procedures and precautions. For the standardized perioperative skincare procedure, four recommendations were listed according to different stages during NI-EBD procedures. CONCLUSION: These recommendations create the 'Expert Consensus on Perioperative Integrated Skincare for Noninvasive Energy-Based Device Aesthetic Procedures in Clinical Practice in China'.

ICTV Virus Taxonomy Profile: Simuloviridae 2023.

The family Simuloviridae includes tailless icosahedral viruses with an internal lipid membrane. The capsid is constructed from two major capsid proteins, both with a single jelly-roll fold. The genome is a circular dsDNA molecule of 16-19 kb. All members infect halophilic archaea in the class Halobacteria (phylum Euryarchaeota) and are temperate viruses, their proviruses residing in host cells as extrachromosomal episomes. Once the lytic life cycle is triggered, production of virions causes cell lysis. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Simuloviridae, which is available at ictv.global/report/simuloviridae.

Prolonged anesthesia induces neuroinflammation and complement-mediated microglial synaptic elimination involved in neurocognitive dysfunction and anxiety-like behaviors.

BACKGROUND: Perioperative neurocognitive disorders (PND) with a high incidence frequently occur in elderly surgical patients closely associated with prolonged anesthesia-induced neurotoxicity. The neuromorphopathological underpinnings of anesthesia-induced neurotoxicity have remained elusive. METHODS: Prolonged anesthesia with sevoflurane was used to establish the sevoflurane-induced neurotoxicity (SIN) animal model. Morris water maze, elevated plus maze, and open field test were employed to track SIN rats' cognitive behavior and anxiety-like behaviors. We investigated the neuropathological basis of SIN through techniques such as transcriptomic, electrophysiology, molecular biology, scanning electron microscope, Golgi staining, TUNEL assay, and morphological analysis. Our work further clarifies the pathological mechanism of SIN by depleting microglia, inhibiting neuroinflammation, and C1q neutralization. RESULTS: This study shows that prolonged anesthesia triggers activation of the NF-κB inflammatory pathway, neuroinflammation, inhibition of neuronal excitability, cognitive dysfunction, and anxiety-like behaviors. RNA sequencing found that genes of different types of synapses were downregulated after prolonged anesthesia. Microglial migration, activation, and phagocytosis were enhanced. Microglial morphological alterations were also observed. C1qa, the initiator of the complement cascade, and C3 were increased, and C1qa tagging synapses were also elevated. Then, we found that the "Eat Me" complement pathway mediated microglial synaptic engulfment in the hippocampus after prolonged anesthesia. Afterward, synapses were remarkably lost in the hippocampus. Furthermore, dendritic spines were reduced, and their genes were also downregulated. Depleting microglia ameliorated the activation of neuroinflammation and complement and rescued synaptic loss, cognitive dysfunction, and anxiety-like behaviors. When neuroinflammatory inhibition or C1q neutralization occurred, complement was also decreased, and synaptic elimination was interrupted. CONCLUSIONS: These findings illustrated that prolonged anesthesia triggered neuroinflammation and complement-mediated microglial synaptic engulfment that pathologically caused synaptic elimination in SIN. We have demonstrated the neuromorphopathological underpinnings of SIN, which have direct therapeutic relevance for PND patients.

STING-IFN-I pathway relieves incision induced acute postoperative pain via inhibiting the neuroinflammation in dorsal root ganglion of rats.

BACKGROUND: The purpose of this study was to study the effect of STING-IFN-I pathway on incision induced postoperative pain in rats and its possible mechanisms. METHODS: The pain thresholds were evaluated by measuring the mechanical withdrawal threshold and the thermal withdrawal latency. The satellite glial cell and macrophage of DRG were analyzed. The expression of STING, IFN-a, P-P65, iNOS, TNF-α, IL-1ß and IL-6 in DRG was evaluated. RESULTS: The activation of STING-IFN-I pathway can reduce the mechanical hyperalgesia, thermal hyperalgesia, down-regulate the expression of P-P65, iNOS, TNF-α, IL-1ß and IL-6, and inhibit the activation of satellite glial cell and macrophage in DRG. CONCLUSIONS: The activation of STING-IFN-I pathway can alleviate incision induced acute postoperative pain by inhibiting the activation of satellite glial cell and macrophage, which reducing the corresponding neuroinflammation in DRG.

The effect of anesthetic depth on postoperative delirium in older adults: a systematic review and meta-analysis.

BACKGROUND: Postoperative delirium (POD) is an important complication for older patients and recent randomised controlled trials have showed a conflicting result of the effect of deep and light anesthesia. METHODS: We included randomised controlled trials including older adults that evaluated the effect of anesthetic depth on postoperative delirium from PubMed, Embase, Web of Science and Cochrane Library. We considered deep anesthesia as observer's assessment of the alertness/ sedation scale (OAA/S) of 0-2 or targeted bispectral (BIS) < 45 and the light anesthesia was considered OAA/S 3-5 or targeted BIS > 50. The primary outcome was incidence of POD within 7 days after surgery. And the secondary outcomes were mortality and cognitive function 3 months or more after surgery. The quality of evidence was assessed via the grading of recommendations assessment, development, and evaluation approach. RESULTS: We included 6 studies represented 7736 patients aged 60 years and older. We observed that the deep anesthesia would not increase incidence of POD when compared with the light anesthesia when 4 related studies were pooled (OR, 1.40; 95% CI, 0.63-3.08, P = 0.41, I2 = 82%, low certainty). And no significant was found in mortality (OR, 1.12; 95% CI, 0.93-1.35, P = 0.23, I2 = 0%, high certainty) and cognitive function (OR, 1.13; 95% CI, 0.67-1.91, P = 0.64, I2 = 13%, high certainty) 3 months or more after surgery between deep anesthesia and light anesthesia. CONCLUSIONS: Low-quality evidence suggests that light general anesthesia was not associated with lower POD incidence than deep general anesthesia. And High-quality evidence showed that anesthetic depth did not affect the long-term mortality and cognitive function. SYSTEMATIC REVIEW REGISTRATION: CRD42022300829 (PROSPERO).

The Crosstalk between the Blood-Brain Barrier Dysfunction and Neuroinflammation after General Anaesthesia.

As we know, with continuous medical progress, the treatment of many diseases can be conducted via surgery, which often relies on general anaesthesia for its satisfactory performance. With the widespread use of general anaesthetics, people are beginning to question the safety of general anaesthesia and there is a growing interest in central nervous system (CNS) complications associated with anaesthetics. Recently, abundant evidence has suggested that both blood-brain barrier (BBB) dysfunction and neuroinflammation play roles in the development of CNS complications after anaesthesia. Whether there is a crosstalk between BBB dysfunction and neuroinflammation after general anaesthesia, and whether this possible crosstalk could be a therapeutic target for CNS complications after general anaesthesia needs to be clarified by further studies.

Charge state depletion nanoscopy with a nitrogen-vacancy center in nanodiamonds.

The development of super-resolution imaging has driven research into biological labeling, new materials' characterization, and nanoscale sensing. Here, we studied the photoinduced charge state conversion of nitrogen-vacancy (NV) centers in nanodiamonds (NDs), which show the potential for multifunction sensing and labeling at the nanoscale. Charge state depletion (CSD) nanoscopy is subsequently demonstrated for the diffraction-unlimited imaging of NDs in biological cells. A resolution of 77 nm is obtained with 50 nm NDs. The depletion laser power of CSD nanoscopy is approximately 1/16 of stimulated emission depletion (STED) microscopy with the same resolution. The results can be used to improve the spatial resolution of biological labeling and sensing with NDs and other nanoparticles.

Emerging roles of mechanosensitive ion channels in acute lung injury/acute respiratory distress syndrome.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a devastating respiratory disorder with high rates of mortality and morbidity, but the detailed underlying mechanisms of ALI/ARDS remain largely unknown. Mechanosensitive ion channels (MSCs), including epithelial sodium channel (ENaC), Piezo channels, transient receptor potential channels (TRPs), and two-pore domain potassium ion (K2P) channels, are highly expressed in lung tissues, and the activity of these MSCs can be modulated by mechanical forces (e.g., mechanical ventilation) and other stimuli (e.g., LPS, hyperoxia). Dysfunction of MSCs has been found in various types of ALI/ARDS, and MSCs play a key role in regulating alveolar fluid clearance, alveolar epithelial/endothelial barrier function, the inflammatory response and surfactant secretion in ALI/ARDS lungs. Targeting MSCs exerts therapeutic effects in the treatment of ALI/ARDS. In this review, we summarize the structure and functions of several well-recognized MSCs, the role of MSCs in the pathogenesis of ALI/ARDS and recent advances in the pharmacological and molecular modulation of MSCs in the treatment of ALI/ARDS. According to the current literature, targeting MSCs might be a very promising therapeutic approach against ALI/ARDS.

Risk factors of perinatal depression in women: a systematic review and meta-analysis.

BACKGROUND: Perinatal depression in women is associated with high morbidity and mortality, and has attracted increasing attention. The investigation of risk factors of perinatal depression in women may contribute to the early identification of depressed or depression-prone women in clinical practice. MATERIAL AND METHODS: A computerized systematic literature search was made in Cochrane Library, PubMed, Web of Science, and EMBASE from January 2009 to October 2021. All included articles were published in English, which evaluated factors influencing perinatal depression in women. Based on the recommendations of the Cochrane Collaboration protocols, Review Manager 5.3 was used as a statistical platform. RESULTS: Thirty-one studies with an overall sample size of 79,043 women were included in the review. Educational level (P = 0.0001, odds ratio [OR]: 1.40, 95% CI: [1.18,1.67]), economic status of families (P = 0.0001, OR: 1.69, 95%CI: [1.29,2.22]), history of mental illness (P < 0.00001, OR: 0.29, 95% CI: [0.18, 0.47]), domestic violence (P < 0.00001, OR: 0.24, 95% CI: [0.17,0.34]), perinatal smoking or drinking (P = 0.005, OR: 0.63; 95% CI [0.45, 0.87]; P = 0.008, OR: 0.43, 95% CI, [0.23 to 0.80]; respectively), and multiparity(P = 0.0003, OR: 0.74, 95% CI: [0.63, 0.87]) were correlated with perinatal depression in women. The stability of our pooled results was verified by sensitivity analysis and publication bias was not observed based on funnel plot results. CONCLUSION: Lower educational level, poor economic status of families, history of mental illness, domestic violence, perinatal smoking or drinking, and multiparity serve as risk factors of perinatal depression in women.

Will repeated Intense Pulsed Light (IPL) treatment sessions affect facial skin sensitivity? Results of a twelve-Month, prospective, randomized split-face study.

BACKGROUND: Despite the widespread use of intense pulsed light (IPL) technology in cosmetic dermatology, the effects of its repeated use on facial skin sensitivity in healthy individuals remains unknown. METHODS: Seventeen healthy female volunteers were included in the study. We measured objective biophysical parameters of the skin, including transepidermal water loss (TEWL), skin glossiness, thickness and density of the epidermis and dermis, sensory nerve current perception threshold (CPT), and regional blood flow before and after treatment at different time points. RESULTS: Sixteen volunteers completed a follow-up of 12 months. The treated side of the face showed a decreased TEWL on D1 and D3, which reverted to normal on D7. Epidermal thickness increased and skin glossiness decreased on the treated side on D1, but returned to normal on D3. We found no statistically significant differences in CPT values or in regional blood flow volume and velocity, with the exception of D1, which exhibited a higher regional blood flow volume on the treated side. CONCLUSION: Repeated IPL treatments had no effects on facial skin barrier function, skin nerve sensitivity, or local microcirculation among healthy individuals. IPL is a safe skin care procedure that does not affect skin sensitivity.

Procedural analgesic interventions in China: a national survey of 2198 hospitals.

BACKGROUND: Humane treatment requires the provision of appropriate sedation and analgesia during medical diagnosis and treatment. However, limited information is available about the status of procedural analgesic interventions in Chinese hospitals. Therefore, a nationwide survey was established to identify challenges and propose potential improvement strategies. METHODS: Forty-three members of the Pain Group of Chinese Society of Anesthesiology established and reviewed the questionnaire, which included (1) general information on the hospitals, (2) the sedation/analgesia rate in gastrointestinal endoscopy, labor, flexible bronchoscopy, hysteroscopy in China, (3) staff assignments, (4) drug use for procedural analgesic interventions, and (5) difficulties in procedural analgesic interventions. The data were obtained using an online questionnaire sent to the chief anesthesiologists of Chinese hospitals above Grade II or members of the Pain Group of Chinese Society of Anesthesiology. RESULTS: Valid and complete questionnaires were received from 2198 (44.0%) hospitals, of which 64.5% were Grade III. The overall sedation/analgesia rates were as follows: gastroscopy (50.6%), colonoscopy (53.7%), ERCP (65.9%), induced abortion (67.5%), labor (42.3%), hysteroscopy (67.0%) and fiber bronchoscopy (52.6%). Compared with Grade II hospitals, Grade III hospitals had a higher proportion of procedural analgesic interventions services except for induced abortion. On average (median [IQR]), each anesthesiologist performed 5.7 [2.3-11.4] cases per day, with 7.3 [3.2-13.6] performed in Grade III hospitals and 3.4 [1.8-6.8] performed in Grade II hospitals (z = -7.065, p < 0.001). CONCLUSIONS: Chinese anesthesiologists have made great efforts to achieve procedural analgesic interventions, as evidenced by the increased rate. The uneven health care provided by hospitals at different levels and in different regions and the lack of anesthesiologists are the main barriers to optimal procedural analgesic interventions.

The role of anesthesiologists' perceived self-efficacy in anesthesia-related adverse events.

BACKGROUND: Self-efficacy, as the vital determinant of behavior, influencing clinicians' situation awareness, work performance, and medical decision-making, might affect the incidence of anesthesia-related adverse events (ARAEs). This study was employed to evaluate the association between perceived self-efficacy level and ARAEs. METHODS: A cross-sectional study was performed in the form of an online self-completion questionnaire-based survey. Self-efficacy was evaluated via validated 4-point Likert scales. Internal reliability and validity of both scales were also estimated via Cronbach's alpha and validity analysis. According to the total self-efficacy score, respondents were divided into two groups: normal level group and high level group. Propensity score matching and multivariable logistic regression were employed to identify the relationship between self-efficacy level and ARAEs. RESULTS: The response rate of this study was 34%. Of the 1011 qualified respondents, 38% were women. The mean (SD) age was 35.30 (8.19) years. The Cronbach's alpha of self-efficacy was 0.92. The KMO (KMO and Bartlett's test) value of the scale was 0.92. ARAEs occurred in 178 (33.0%) of normal level self-efficacy group and 118 (25.0%) of high level self-efficacy group. Before adjustment, high level self-efficacy was associated with a decreased incidence of ARAEs (RR [relative risk], 0.76; 95% CI [confidence interval], 0.62-0.92). After adjustment, high level self-efficacy was also associated with a decreased incidence of ARAEs (aRR [adjusted relative risk], 0.63, 95% CI, 0.51-0.77). In multivariable logistic regression, when other covariates including years of experience, drinking, and the hospital ranking were controlled, self-efficacy level (OR [odds ratio], 0.62; 95% CI, 0.46-0.82; P = 0.001) was significantly correlated with ARAEs. CONCLUSIONS: Our results found a clinically meaningful and statistically significant correlation between self-efficacy and ARAEs. These findings partly support medical educators and governors in enhancing self-efficacy construction in clinical practice and training.

Influence of genetic variants on remifentanil sensitivity in Chinese women.

WHAT IS KNOWN AND OBJECTIVE: Significant individual differences have been observed in pain sensitivity and analgesic effect of opioids. Previous studies have shown that genetic factors contributed to analgesics requirement obviously. Therefore, we investigated the role of genetic polymorphisms in the sensitivity to the analgesic effect of remifentanil in this study. METHODS: One hundred thirty-seven patients undergoing gynaecological surgery were observed. Before procedures, we measured the basal pain threshold of each patient, including the pressure pain threshold and pressure pain tolerance threshold. Subsequently, patients received a continuous remifentanil infusion for 15 min at a constant rate of 0.2 µg/(kg min). The pain thresholds were measured again after the remifentanil infusion. Moreover, respiratory depression was estimated using oxygen saturation during infusion. DNA was extracted from peripheral venous blood and genotyped using SNaPshot technology. RESULTS AND DISCUSSION: Polymorphisms were found in genes associated with the individual variation in analgesia. Participants carrying OPRM1 rs9397685 AA, ADRB1 rs1801253 CC, and GCH1 rs8007267 CC polymorphisms showed higher sensitivity to analgesic effect induced by remifentanil, and the participants carrying the OPRD1 rs2234918 TT showed lower sensitivity to remifentanil-related respiratory depression. Moreover, individual susceptibility to remifentanil increases with age. WHAT IS NEW AND CONCLUSION: Gene variation in OPRM1 rs9397685 AA, ADRB1 rs1801253 CC, GCH1 rs8007267 CC, and OPRD1 rs2234918 TT were related to the conspicuous interindividual differences in the analgesia and respiratory depression of remifentanil, mainly by affecting the target protein receptors and relative metabolic enzymes.

Ganoderma lucidum polysaccharides ameliorate lipopolysaccharide-induced acute pneumonia via inhibiting NRP1-mediated inflammation.

CONTEXT: Ganoderma lucidum polysaccharides (GLP), from Ganoderma lucidum (Leyss. ex Fr.) Karst. (Ganodermataceae), are reported to have anti-inflammatory effects, including anti-neuroinflammation and anti-colitis. Nevertheless, the role of GLP in acute pneumonia is unknown. OBJECTIVE: To explore the protective role of GLP against LPS-induced acute pneumonia and investigate possible mechanisms. MATERIALS AND METHODS: GLP were extracted and used for high-performance liquid chromatography (HPLC) analysis after acid hydrolysis and PMP derivatization. Sixty C57BL/6N male mice were randomly divided into six groups: Sham, Model, LPS + GLP (25, 50 and 100 mg/kg/d administered intragastrically for two weeks) and LPS + dexamethasone (6 mg/kg/d injected intraperitoneally for one week). Acute pneumonia mouse models were established by intratracheal injection of LPS. Haematoxylin and eosin (H&E) staining was examined to evaluate lung lesions. ELISA and quantitative real-time PCR were employed to assess inflammatory factors expression. Western blots were carried out to measure Neuropilin-1 expression and proteins related to apoptosis and autophagy. RESULTS: GLP suppressed inflammatory cell infiltration. In BALF, cell counts were 1.1 × 106 (model) and 7.1 × 105 (100 mg/kg). Release of GM-CSF and IL-6 was reduced with GLP (25, 50 and 100 mg/kg) treatment. The expression of genes IL-1ß, IL-6, TNF-α and Saa3 was reduced. GLP treatment also suppressed the activation of Neuropilin-1 (NRP1), upregulated the levels of Bcl2/Bax and LC3 and led to downregulation of the ratio C-Caspase 3/Caspase 3 and P62 expression. DISCUSSION AND CONCLUSIONS: GLP could protect against LPS-induced acute pneumonia through multiple mechanisms: blocking the infiltration of inflammatory cells, inhibiting cytokine secretion, suppressing NRP1 activation and regulating pneumonocyte apoptosis and autophagy.