Nuclear Quantum Effects on Nonadiabatic Dynamics of a Green Fluorescent Protein Chromophore Analogue: Ring-Polymer Surface-Hopping Simulation.

Herein, we have used the "on-the-fly" ring-polymer surface-hopping simulation method with the centroid approximation (RPSH-CA), in combination with the multireference OM2/MRCI electronic structure calculations to study the photoinduced dynamics of a green fluorescent protein (GFP) chromophore analogue in the gas phase, i.e., o-HBI, at 50, 100, and 300 K with 1, 5, 10, and 15 beads (3600 1 ps trajectories). The electronic structure calculations identified five new minimum-energy conical intersection (MECI) structures, which, together with the previous one, play crucial roles in the excited-state decay dynamics of o-HBI. It is also found that the excited-state intramolecular proton transfer (ESIPT) occurs in an ultrafast manner and is completed within 20 fs in all the simulation conditions because there is no barrier associated with this ESIPT process in the S1 state. However, the other excited-state dynamical results are strongly related to the number of beads. At 50 and 100 K, the nuclear quantum effects (NQEs) are very important; therefore, the excited-state dynamical results change significantly with the bead number. For example, the S1 decay time deduced from time-dependent state populations becomes longer as the bead number increases. Nevertheless, an essentially convergent trend is observed when the bead number is close to 10. In contrast, at 300 K, the NQEs become weaker and the above dynamical results converge very quickly even with 1 bead. Most importantly, the NQEs seriously affect the excited-state decay mechanism of o-HBI. At 50 and 100 K, most trajectories decay to the S0 state via perpendicular keto MECIs, whereas, at 300 K, only twisted keto MECIs are responsible for the excited-state decay. The present work not only comprehensively explores the temperature-dependent photoinduced dynamics of o-HBI, but also demonstrates the importance and necessity of NQEs in nonadiabatic dynamics simulations, especially at relatively low temperatures.

Iron-driven self-assembly of dopamine into dumbbell-shaped nanozyme for visual and rapid detection of norfloxacin on a smartphone-assisted platform.

Antibiotics in aquatic environments raise health concerns. Therefore, the rapid, on-site, and accurate detection of antibiotic residues is crucial for protecting the environment and human health. Herein, a dumbbell-shaped iron (Fe3+)-dopamine coordination nanozyme (Fe-DCzyme) was developed via an iron-driven self-assembly strategy. It exhibited excellent peroxidase-like activity, which can be quenched by adding l-cysteine to prevent Fe3+/Fe2+ electron transfer but restored by adding norfloxacin. Given the 'On-Off-On' effect of peroxidase-like activity, Fe-DCzyme was used as a colourimetric sensor for norfloxacin detection, and showed a wide linear range from 0.05 to 6.00 µM (R2 = 0.9950) and LOD of 27.0 nM. A portable smartphone-assisted detection platform using Fe-DCzyme was also designed to convert norfloxacin-induced color changes into RGB values as well as to realise the rapid, on-site and quantitative detection of norfloxacin. A good linear relation (0.10-6.00 µM) and high sensitivity (LOD = 79.3 nM) were achieved for the smartphone-assisted Fe-DCzyme detection platform. Its application was verified using norfloxacin spiking methods with satisfactory recoveries (92.66%-119.65%). Therefore, the portable smartphone-assisted Fe-DCzyme detection platform with low cost and easy operation can be used for the rapid, on-site and visual quantitative detection of antibiotic residues in water samples.

[Spatial-temporal Distribution and Source Analysis of Polycyclic Aromatic Hydrocarbons in the Sediments of Poyang Lake].

The concentrations, spatial-temporal distribution, and influencing factors of 16 polycyclic aromatic hydrocarbons (PAHs) in the sediments of Poyang Lake were studied, and a quantitative source analysis of PAHs in different areas of the lake was conducted. PAHs were widespread within the sediments. The concentrations of ∑16PAHs in the surface sediments of all sites ranged from 203 to 2 318 µg·kg-1. The concentrations of PAHs in the surface sediments of the lake body were higher than those in the surface sediments of the inlet rivers. The ratio of PAHs in Poyang Lake was 4 rings > 5 rings > 6 rings > 3 rings > 2 rings; the composition of 4-ring PAHs was dominant, and its content accounted for 86.11% of ∑16PAHs. The 2- and 3-ring and some 4-ring PAHs, including Flua and Pyr, were more susceptible to SOM, and the 4 through 6-ring PAHs were more susceptible to ORP and heavy metals and other environmental factors. Spatially, the higher concentration of ∑16PAHs occurred in the area of the lake adjacent to Duchang County and Poyang County, where the terrain was relatively closed, and the water exchange with the surrounding area was less than that in other sections, which was not conducive to the migration, transformation, and degradation of pollutants. In the temporal distribution, the changes in PAHs concentration level and the development of GDP in Jiangxi Province showed high consistency, and the influence of economic development and human activities might have been the main reason for the increasing PAHs concentration level. The main sources of PAHs in surface sediments of Poyang Lake included petroleum pollution and oil and coal and biomass combustion sources, and there were some spatial differences in PAHs sources in different regions. This study can provide a reference for PAHs pollution in surface sediments of Poyang Lake, which is important for the ecological environmental protection and management of Poyang Lake.

TIGAR reduces neuronal ferroptosis by inhibiting succinate dehydrogenase activity in cerebral ischemia.

Ischemia Stroke (IS) is an acute neurological condition with high morbidity, disability, and mortality due to a severe reduction in local cerebral blood flow to the brain and blockage of oxygen and glucose supply. Oxidative stress induced by IS predisposes neurons to ferroptosis. TP53-induced glycolysis and apoptosis regulator (TIGAR) inhibits the intracellular glycolytic pathway to increase pentose phosphate pathway (PPP) flux, promotes NADPH production and thus generates reduced glutathione (GSH) to scavenge reactive oxygen species (ROS), and thus shows strong antioxidant effects to ameliorate cerebral ischemia/reperfusion injury. However, in the current study, prolonged ischemia impaired the PPP, and TIGAR was unable to produce NADPH but was still able to reduce neuronal ferroptosis and attenuate ischemic brain injury. Ferroptosis is a form of cell death caused by free radical-driven lipid peroxidation, and the vast majority of ROS leading to oxidative stress are generated by mitochondrial succinate dehydrogenase (SDH) driving reverse electron transfer (RET) via the mitochondrial electron transport chain. Overexpression of TIGAR significantly inhibited hypoxia-induced enhancement of SDH activity, and TIGAR deficiency further enhanced SDH activity. We also found that the inhibitory effect of TIGAR on SDH activity was related to its mitochondrial translocation under hypoxic conditions. TIGAR may inhibit SDH activity by mediating post-translational modifications (acetylation and succinylation) of SDH A through interaction with SDH A. SDH activity inhibition reduces neuronal ferroptosis by decreasing ROS production, eliminating MitoROS levels and attenuating lipid peroxide accumulation. Notably, TIGAR-mediated inhibition of SDH activity and ferroptosis was not dependent on the PPP-NADPH-GPX4 pathways. In conclusion, mitochondrial translocation of TIGAR in prolonged ischemia is an important pathway to reduce neuronal ferroptosis and provide sustainable antioxidant defense for the brain under prolonged ischemia, further complementing the mechanism of TIGAR resistance to oxidative stress induced by IS.

Mammalian integrated stress responses in stressed organelles and their functions.

The integrated stress response (ISR) triggered in response to various cellular stress enables mammalian cells to effectively cope with diverse stressful conditions while maintaining their normal functions. Four kinases (PERK, PKR, GCN2, and HRI) of ISR regulate ISR signaling and intracellular protein translation via mediating the phosphorylation of eukaryotic translation initiation factor 2 α (eIF2α) at Ser51. Early ISR creates an opportunity for cells to repair themselves and restore homeostasis. This effect, however, is reversed in the late stages of ISR. Currently, some studies have shown the non-negligible impact of ISR on diseases such as ischemic diseases, cognitive impairment, metabolic syndrome, cancer, vanishing white matter, etc. Hence, artificial regulation of ISR and its signaling with ISR modulators becomes a promising therapeutic strategy for relieving disease symptoms and improving clinical outcomes. Here, we provide an overview of the essential mechanisms of ISR and describe the ISR-related pathways in organelles including mitochondria, endoplasmic reticulum, Golgi apparatus, and lysosomes. Meanwhile, the regulatory effects of ISR modulators and their potential application in various diseases are also enumerated.

The Multiple Roles of Autophagy in Neural Function and Diseases.

Autophagy involves the sequestration and delivery of cytoplasmic materials to lysosomes, where proteins, lipids, and organelles are degraded and recycled. According to the way the cytoplasmic components are engulfed, autophagy can be divided into macroautophagy, microautophagy, and chaperone-mediated autophagy. Recently, many studies have found that autophagy plays an important role in neurological diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, neuronal excitotoxicity, and cerebral ischemia. Autophagy maintains cell homeostasis in the nervous system via degradation of misfolded proteins, elimination of damaged organelles, and regulation of apoptosis and inflammation. AMPK-mTOR, Beclin 1, TP53, endoplasmic reticulum stress, and other signal pathways are involved in the regulation of autophagy and can be used as potential therapeutic targets for neurological diseases. Here, we discuss the role, functions, and signal pathways of autophagy in neurological diseases, which will shed light on the pathogenic mechanisms of neurological diseases and suggest novel targets for therapies.

Surface reconstruction of RuO2/Co3O4 amorphous-crystalline heterointerface for efficient overall water splitting.

The rational construction of amorphous-crystalline heterointerface can effectively improve the activity and stability of hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Herein, RuO2/Co3O4 (RCO) amorphous-crystalline heterointerface is prepared via oxidation method. The optimal RCO-10 exhibits low overpotentials of 57 and 231 mV for HER and OER at 10 mA cm-2, respectively. Experimental characterization and density functional theory (DFT) results show that the optimized electronic structure and surface reconstruction endow RCO-10 with excellent catalytic activity. DFT results show that electrons transfer from RuO2 to Co3O4 through the amorphous-crystalline heterointerface, achieving electron redistribution and moving the d-band center upward, which optimizes the adsorption free energy of the hydrogen reaction intermediate. Moreover, the reconstructed Ru/Co(OH)2 during the HER process has low hydrogen adsorption free energy to enhance HER activity. The reconstructed RuO2/CoOOH during the OER process has a low energy barrier for the elementary reaction (O*→*OOH) to enhance OER activity. Furthermore, RCO-10 requires only 1.50 V to drive 10 mA cm-2 and maintains stability over 200 h for overall water splitting. Meanwhile, RCO-10 displays stability for 48 h in alkaline solutions containing 0.5 M NaCl. The amorphous-crystalline heterointerface may bring new breakthroughs in the design of efficient and stable catalysts.

Establishment of a TaqMan-based real-time quantitative PCR method for detection of exogenous fowl adenovirus type â , type â ¢ and avian leukosis virus in human cold adapted live attenuated influenza vaccines.

Cold adapted live attenuated influenza vaccines can effectively prevent human disease and death caused by influenza virus. Since chicken embryos are used as the culture substrate for the large-scale production of influenza vaccines, cold adapted live attenuated influenza vaccines may be contaminated by exogenous avian viruses. Rapid and sensitive methods such as TaqMan-based quantitative PCR are needed for the detection of exogenous avian viruses during cold adapted live attenuated influenza vaccines production. In this study, a TaqMan-based quantitative PCR method was established for the detection of three common exogenous avian viruses, including fowl adenovirus type I, type Ⅲ and avian leukosis virus. Avian virus-encoding plasmids purified in high-performance liquid chromatography were essential for sensitivity analysis. The sensitivity reached 1 copy per reaction for each of the avian virus plasmids. Standard curves showed a strong linear relationship. The TaqMan-based quantitative PCR method had high specificity and no cross-reactivity with other irrelevant viruses. Furthermore, the established TaqMan-based quantitative PCR can effectively detect 0.1 TCID50 of each avian virus without or with interference from the influenza virus nucleic acid. Ultimately, this method was used to test three master seed lots of monovalent cold adapted live attenuated influenza vaccine, and the results showed that no fowl adenovirus type I, type Ⅲ or avian leukosis virus contamination, which were consistent with serological methods. The TaqMan-based quantitative PCR method for the determination of extraneous avian viruses in cold adapted live attenuated influenza vaccines met the requirement for both conventional and emergency inspection on cold adapted live attenuated influenza vaccines.

[Augmenting locking plate with autologous bone graft for the treatment of nonunion of long bone fracture in the lower extremity with retaining of the original intramedullary nail].

OBJECTIVE: To explore clinical effect of attaching locking plate with bone grafting based on retaining the original intramedullary nail in treating non-union after intramedullary nail fixation of long shaft fractures of lower limbs. METHODS: A retrospective study was conducted on 20 patients treated with non-union fractures after intramedullary nailing of long shaft fractures of lower limbs from June 2015 to June 2020. All patients were treated with the original intramedullary nailing and bone grafting from the iliac bone, and were underwent open reduction plate internal fixation and bone grafting for old fractures. Among them, 14 were males and 6 were females, aged from 35 to 56 years old with an average of (42.2±9.6) years old. Nine patients were femoral shaft fracture and 11 patients were tibial shaft fracture. According to characteristics of fracture end nonunion, 6 patients were stable/atrophic, 9 patients were unstable/large, and 5 patients were unstable/atrophic. The nonunion time ranged from 8 to 12 months with an average of(9.8±2.0) months after the initial surgery. Visual analogue scale (VAS), knee range of motion, bone healing time, complications and fracture-end healing were recorded before and at the latest follow-up. RESULTS: All patients were followed up for 18 to 48 months with an average of (36.3±10.5) months. The incision of all patients were healed at stageⅠwithout complications such as infection or internal fixation ruptur. Healing time of femur and tibia was (8.5±2.6) months and (9.5±2.2) months. Knee joint motion increased from preoperative (101.05±8.98) ° to postoperative (139.35±8.78) ° at the latest follow-up (t=-12.845, P<0.001). VAS decreased from preoperative (5.15±1.72) to postoperative (0.75±0.96) at the latest follow-up (t=11.186, P<0.001). CONCLUSION: On the basis of retaining the original intramedullary nail, the addition of locking plate internal fixation and autogenous iliac bone grafting have advantages of simple operation, less trauma, fewer complications and high fracture healing rate. It is one of the effective surgical schemes for the treatment of nonunion after intramedullary nail fixation of long bone fracture of lower extremity.

Exogenous NADPH exerts a positive inotropic effect and enhances energy metabolism via SIRT3 in pathological cardiac hypertrophy and heart failure.

BACKGROUND: Therapies are urgently required to ameliorate pathological cardiac hypertrophy and enhance cardiac function in heart failure. Our preliminary experiments have demonstrated that exogenous NADPH exhibits a positive inotropic effect on isolated heart. This study aims to investigate the positive inotropic effects of NADPH in pathological cardiac hypertrophy and heart failure, as well as the underlying mechanisms involved. METHODS: Endogenous plasma NADPH contents were determined in patients with chronic heart failure and control adults. The positive inotropic effects of NADPH were investigated in isolated toad heart or rat heart. The effects of NADPH were investigated in isoproterenol (ISO)-induced cardiac hypertrophy or transverse aortic constriction (TAC)-induced heart failure. The underlying mechanisms of NADPH were studied using SIRT3 knockout mice, echocardiography, Western blotting, transmission electron microscopy, and immunoprecipitation. FINDINGS: The endogenous NADPH content in the blood of patients and animals with pathological cardiac hypertrophy or heart failure was significantly reduced compared with age-sex matched control subjects. Exogenous NADPH showed positive inotropic effects on the isolated normal and failing hearts, while antagonism of ATP receptor partially abolished the positive inotropic effect of NADPH. Exogenous NADPH administration significantly reduced heart weight indices, and improved cardiac function in the mice with pathological cardiac hypertrophy or heart failure. NADPH increased SIRT3 expression and activity, deacetylated target proteins, improved mitochondrial function and facilitated ATP production in the hypertrophic myocardium. Importantly, inhibition of SIRT3 abolished the positive inotropic effect of NADPH, and the anti-heart failure effect of NADPH was significantly reduced in the SIRT3 Knockout mice. INTERPRETATION: Exogenous NADPH shows positive inotropic effect and improves energy metabolism via SIRT3 in pathological cardiac hypertrophy and heart failure. NADPH thus may be one of the potential candidates for the treatment of pathological cardiac hypertrophy or heart failure. FUNDING: This work was supported by grants from the National Natural Science Foundation of China (No. 81973315, 82173811, 81730092), Natural Science Foundation of Jiangsu Higher Education (20KJA310008), Jiangsu Key Laboratory of Neuropsychiatric Diseases (BM2013003) and the Priority Academic Program Development of the Jiangsu Higher Education Institutes (PAPD).

Effects of Oxygen Pressure on the Microstructures and Nanomechanical Properties of Samarium-Doped BiFeO3 Thin Films.

In this study, samarium (Sm-10at%)-doped BiFeO3 (SmBFO) thin films were grown on platinum-coated glass substrates using pulsed laser deposition (PLD) to unveil the correlation between the microstructures and nanomechanical properties of the films. The PLD-derived SmBFO thin films were prepared under various oxygen partial pressures (PO2) of 10, 30, and 50 mTorr at a substrate temperature of 600 °C. The scanning electron microscopy analyses revealed a surface morphology consisting of densely packed grains, although the size distribution varied with the PO2. X-ray diffraction results indicate that all SmBFO thin films are textured and preferentially oriented along the (110) crystallographic orientation. The crystallite sizes of the obtained SmBFO thin films calculated from the Scherrer and (Williamson-Hall) equations increased from 20 (33) nm to 25 (52) nm with increasing PO2. In addition, the nanomechanical properties (the hardness and Young's modulus) of the SmBFO thin films were measured by using nanoindentation. The relationship between the hardness and crystalline size of SmBFO thin films appears to closely follow the Hall-Petch equation. In addition, the PO2 dependence of the film microstructure, the crystallite size, the hardness, and Young's modulus of SmBFO thin films are discussed.

Lepr-Expressing PDLSCs Contribute to Periodontal Homeostasis and Respond to Mechanical Force by Piezo1.

Periodontium supports teeth in a mechanically stimulated tissue environment, where heterogenous stem/progenitor populations contribute to periodontal homeostasis. In this study, Leptin receptor+ (Lepr+) cells are identified as a distinct periodontal ligament stem cell (PDLSC) population by single-cell RNA sequencing and lineage tracing. These Lepr+ PDLSCs are located in the peri-vascular niche, possessing multilineage potential and contributing to tissue repair in response to injury. Ablation of Lepr+ PDLSCs disrupts periodontal homeostasis. Hyper-loading and unloading of occlusal forces modulate Lepr+ PDLSCs activation. Piezo1 is demonstrated that mediates the mechanosensing of Lepr+ PDLSCs by conditional Piezo1-deficient mice. Meanwhile, Yoda1, a selective activator of Piezo1, significantly accelerates periodontal tissue growth via the induction of Lepr+ cells. In summary, Lepr marks a unique multipotent PDLSC population in vivo, to contribute toward periodontal homeostasis via Piezo1-mediated mechanosensing.

Dual Electronic Modulations on NiFeV Hydroxide@FeOx Boost Electrochemical Overall Water Splitting.

Nickel-iron based hydroxides have been proven to be excellent oxygen evolution reaction (OER) electrocatalysts, whereas they are inactive toward hydrogen evolution reaction (HER), which severely limits their large-scale applications in electrochemical water splitting. Herein, a heterostructure consisted of NiFeV hydroxide and iron oxide supported on iron foam (NiFeV@FeOx /IF) has been designed as a highly efficient bifunctional (OER and HER) electrocatalyst. The V doping and intimate contact between NiFeV hydroxide and FeOx not only improve the entire electrical conductivity of the catalyst but also afford more high-valence Ni which serves as active sites for OER. Meanwhile, the introduction of V and FeOx reduces the electron density on lattice oxygen, which greatly facilitates desorption of Hads . All of these endow the NiFeV@FeOx /IF with exceptionally low overpotentials of 218 and 105 mV to achieve a current density of 100 mA cm-2 for OER and HER, respectively. More impressively, the electrolyzer requires an ultra-low cell voltage of 1.57 V to achieve 100 mA cm-2 and displays superior electrochemical stability for 180 h, which outperforms commercial RuO2 ||Pt/C and most of the representative catalysts reported to date. This work provides a unique route for developing high-efficiency electrocatalyst for overall water splitting.

Nonadiabatic Derivative Couplings Calculated Using Information of Potential Energy Surfaces without Wavefunctions: Ab Initio and Machine Learning Implementations.

In this work, we implemented an approximate algorithm for calculating nonadiabatic coupling matrix elements (NACMEs) of a polyatomic system with ab initio methods and machine learning (ML) models. Utilizing this algorithm, one can calculate NACMEs using only the information of potential energy surfaces (PESs), i.e., energies, and gradients as well as Hessian matrix elements. We used a realistic system, namely CH2NH, to compare NACMEs calculated by this approximate PES-based algorithm and the accurate wavefunction-based algorithm. Our results show that this approximate PES-based algorithm can give very accurate results comparable to the wavefunction-based algorithm except at energetically degenerate points, i.e., conical intersections. We also tested a machine learning (ML)-trained model with this approximate PES-based algorithm, which also supplied similarly accurate NACMEs but more efficiently. The advantage of this PES-based algorithm is its significant potential to combine with electronic structure methods that do not implement wavefunction-based algorithms, low-scaling energy-based fragment methods, etc., and in particular efficient ML models, to compute NACMEs. The present work could encourage further research on nonadiabatic processes of large systems simulated by ab initio nonadiabatic dynamics simulation methods in which NACMEs are always required.

[Application of Animal Model Training in Preclinical Skills Teaching for Graduate Students of Dentistry].

Objective: To explore the potential application value of animal model training in improving the comprehensive clinical ability of postgraduate students of dentistry and to provide reference for new methods of preclinical skills teaching. Methods: A total of 40 postgraduate students of dentistry were assigned to two groups, an experimental group and a control group. The control group took the routine teaching course on root canal treatment for the right mandibular first molar, using a simulated model of human head. The experimental group also took a teaching course on root canal therapy for the right mandibular first molar, but an animal model was used for the group. After the course was completed, the instructor conducted comprehensive evaluation of the students' psychological quality, patient communication skills, diagnosis and treatment logic, speed of performing procedures, and treatment plan design. A questionnaire survey was conducted to examine the students' attitudes toward and evaluation of animal model training. Results: The scores for psychological quality (0.430±0.024 vs. 0.115±0.036), patient communication skills (0.878±0.065 vs. 0.115±0.036), diagnosis and treatment logic (0.630±0.066 vs. 0.372±0.033), speed of performing procedures (0.8975±0.019 vs. 0.055±0.080), and treatment plan design (0.539±0.036 vs. 0.396±0.017) of the experimental group were significantly higher than those of the control group ( P<0.0001). The total score of the experimental group (3.374±0.184) was significantly higher than that of the control group (1.053±0.082) and the difference was statistically significant ( P<0.001). 95% of the students in the control group and 100% of those in the experimental group were willing to participate in animal model training to improve their level of diagnosis and treatment skills for dental and endodontic diseases, showing no statistically significant difference ( χ 2=1.026, P=0.3112). In the experimental group, 30% of the students believed that their psychological qualities had been improved, 50% believed that their procedure skills had been improved, and 20% believed that animal model training had expanded the scope of their theoretical knowledge. Conclusion: Adding animal model training can improve dentistry graduate students' comprehensive abilities, including their psychological quality, patient communication skills, diagnosis and treatment logic, speed of performing procedures, and treatment plan design. In addition, it helps students familiarize themselves in advance with animal experimental operations for basic research, thus helping them acquire dual professional skills.

Mitochondria associated ER membranes and cerebral ischemia: Molecular mechanisms and therapeutic strategies.

Endoplasmic reticulum (ER) and mitochondria are two important organelles that are highly dynamic in mammalian cells. The physical connection between them is mitochondria associated ER membranes (MAM). In recent years, studies on endoplasmic reticulum and mitochondria have shifted from independent division to association and comparison, especially MAM has gradually become a research hotspot. MAM connects the two organelles, not only to maintain their independent structure and function, but also to promote metabolism and signal transduction between them. This paper reviews the morphological structure and protein localization of MAM, and briefly analyzes the functions of MAM in regulating Ca2+ transport, lipid synthesis, mitochondrial fusion and fission, endoplasmic reticulum stress and oxidative stress, autophagy and inflammation. Since ER stress and mitochondrial dysfunction are important pathological events in neurological diseases including ischemic stroke, MAM is likely to play an important role in cerebral ischemia by regulating the signaling of the two organelles and the crosstalk of the two pathological events.

Robotics in Cervical Spine Surgery: Feasibility and Safety of Posterior Screw Placement.

OBJECTIVE: Robot-assisted (RA) techniques have been widely investigated in thoracolumbar spine surgery. However, the application of RA methods on cervical spine surgery is rare due to the complex morphology of cervical vertebrae and catastrophic complications. Thus, the feasibility and safety of RA cervical screw placement remain controversial. This study aims to evaluate the feasibility and safety of RA screw placement on cervical spine surgery. METHODS: A comprehensive search on PubMed, Cochrane Library, Embase Database, Web of Science, Chinese National Knowledge Databases, and Wanfang Database was performed to select potential eligible studies. Randomized controlled trials (RCTs), comparative cohort studies, and case series reporting the accuracy of cervical screw placement were included. The Cochrane risk of bias criteria and Newcastle-Ottawa Scale criteria were utilized to rate the risk of bias of the included literatures. The primary outcome was the rate of cervical screw placement accuracy with robotic guidance; subgroup analyses based on the screw type and insertion segments were also performed. RESULTS: One RCT, 3 comparative cohort studies, and 3 case series consisting of 160 patients and 719 cervical screws were included in this meta-analysis. The combined outcomes indicated that the rates of optimal and clinically acceptable cervical screw placement accuracy under robotic guidance were 88.0% (95% confidence interval [CI], 84.1%-91.4%; p = 0.073; I2 = 47.941%) and 98.4% (95% CI, 96.8%-99.5%; p = 0.167; I2 = 35.954%). The subgroup analyses showed that the rate of optimal pedicle screw placement accuracy was 88.2% (95% CI, 83.1%-92.6%; p = 0.057; I2 = 53.305%); the rates of optimal screw placement accuracy on C1, C2, and subaxial segments were 96.2% (95% CI, 80.5%-100.0%; p = 0.167; I2 = 44.134X%), 89.7% (95% CI, 80.6%-96.6%; p = 0.370; I2 = 0.000X%), and 82.6% (95% CI, 70.9%-91.9%; p = 0.057; I2 = 65.127X%;), respectively. CONCLUSION: RA techniques were associated with high rates of optimal and clinically acceptable screw positions. RA cervical screw placement is accurate, safe, and feasible in cervical spine surgery with promising clinical potential.

Neuroprotection of NAD+ and NBP against ischemia/reperfusion brain injury is associated with restoration of sirtuin-regulated metabolic homeostasis.

Background: Ischemic stroke seriously threatens human health because of high rates of morbidity, mortality and disability. This study compared the effects of nicotinamide adenine dinucleotide (NAD+) and butylphthalide (NBP) on in vitro and in vivo ischemic stroke models. Methods: Transient middle cerebral artery occlusion/reperfusion (t-MCAO/R) model was established in mice, and the cultured primary cortical neurons were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Cerebral infarct volume, neurobehavioral indices, antioxidant activity, ATP level and lactic acid content were determined. The neuroprotective effects of NAD+ or NBP were compared using sirtuin inhibitor niacinamide (NAM). Results: Intraperitoneal injection of NBP within 4 h or intravenous injection of NAD+ within 1 h after t-MCAO/R significantly reduced the volume of infarcts, cerebral edema, and neurological deficits. Administration of NAD+ and NBP immediately after t-MCAO/R in mice showed similar neuroprotection against acute and long-term ischemic injury. Both NAD+ and NBP significantly inhibited the accumulation of MDA and H2O2 and reduced oxidative stress. NAD+ was superior to NBP in inhibiting lipid oxidation and DNA damage. Furthermore, although both NAD+ and NBP improved the morphology of mitochondrial damage induced by ischemia/reperfusion, NAD+ more effectively reversed the decrease of ATP and increase of lactic acid after ischemia/reperfusion compared with NBP. NAD+ but not NBP treatment significantly upregulated SIRT3 in the brain, but the sirtuin inhibitor NAM could abolish the protective effect of NAD+ and NBP by inhibiting SIRT1 or SIRT3. Conclusions: These results confirmed the protective effects of NAD+ and NBP on cerebral ischemic injury. NBP and NAD+ showed similar antioxidant effects, while NAD+ had better ability in restoring energy metabolism, possibly through upregulating the activity of SIRT1 and SIRT3. The protection provided by NBP against cerebral ischemia/reperfusion may be achieved through SIRT1.

Etiology and clinical features of non-O1/non-O139 Vibrio cholerae infection in an inland city in China.

Non-O1/non-O139 Vibrio cholerae (NOVC) causes various illnesses ranging in severity from mild to life-threatening but were ignored previously. Knowledge of the NOVC infection, particularly bacteremia, is limited because of its rarity. Here we first retrospectively reported the demographic, clinical, and therapy characteristics of patients with NOVC infection. Isolated NOVC stains were identified by a series of biochemical, mass spectrometry (MS), and serum agglutination tests. The results of 11 patients with NOVC infection (including 8 with bacteremia) with a median age of 68 years were included in this report. Most isolated NOVC strains had antibiotic susceptibility. Patients with NOVC-positive were distributed in various departments, most occurring in gastroenterology (6 cases). Hepatic disease was the most common comorbid disease, followed by diabetes (3 cases) and biliary tract disease (3 cases). Two cases were previously healthy. The most common symptom at presentation was fever. All patients presented with abnormal changes in hematology and inflammatory parameters. Cephalosporins were the most frequently used antibiotics. Ten patients had a favorable outcome after treatment; one died from complicated underlying diseases. In summary, we recommend the timely identification of NOVC strains using MALDI-TOF-MS. The suspicion of NOVC bacteremia cannot be ruled out regardless of the host's immune status. An alternative therapeutic regimen for this infection may be ß-lactam antibiotics or combined with ß-lactamase inhibitors. Regardless, the specific therapeutic regimen should be based on the antibiogram data.

Prenatal diagnosis of fetuses conceived by assisted reproductive technology by karyotyping and chromosomal microarray analysis.

Background: Invasive prenatal evaluation by chromosomal microarray analysis (CMA) and karyotyping might represent an important option in pregnant women, but limited reports have applied CMA and karyotyping of fetuses conceived by assisted reproductive technology (ART). This study aimed to examine the value of CMA and karyotyping in prenatal diagnosis after ART. Methods: This retrospective study included all singleton fetuses conceived by ART from January 2015 to December 2021. Anomalies prenatally diagnosed based on karyotyping and CMA were analyzed. Prevalence rates for various CMA and karyotyping results were stratified based on specific testing indications including isolated-and non-isolated ART groups. The rates of CMA findings with clinical significance (pathogenic/likely pathogenic) and karyotype anomalies were assessed and compared to those of local control individuals with naturally conceived pregnancies and without medical indications. Results: In total, 224 subjects were assessed by karyotyping and CMA. In the examined patients, chromosomal and karyotype abnormality rates were 3.57% (8/224) and 8.93% (20/224), respectively. This finding indicated a 5.35% (12/224)-incremental rate of abnormal CMA was obtained over karyotype analysis (p = 0.019). The risk of CMA with pathogenic findings for all pregnancies conceived by ART (5.80%, 13/224) was markedly elevated in comparison with the background value obtained in control individuals (1.47%, 9/612; p = 0.001). In addition, risk of CMA with clinically pathogenic results in isolated ART groups was significant higher compared to the background risk reported in the control cohort (p = 0.037). Conclusions: Prenatal diagnosis including karyotyping and CMA is recommended for fetuses conceived by ART, with or without ultrasound findings.