Application of Ortho-Bridge System after Femoral Bone Transport.

The bone transport technique uses the principle of distraction-osteogenesis and fill bone defects with the aid of an external fixator. In order to evaluate the clinical effect of femoral internal fixation with Ortho-Bridge System after bone transport, 4 patients after femoral bone transport from October 2020 to October 2022 are studied in this paper. Among them, 3 patients ran refracture of femur after removal of the Limb reconstruction system, 1 patient just finish femoral bone transport and request internal fixation. The surgery results show that Ortho-Bridge System can be used in the situation that conventional Locking compression plate and intramedullary nail are not suitable due to anatomical variation after femoral bone transport. Key words: femoral fracture; Ortho-Bridge System; bone transport; postoperative complications of bone transport.

Scanning the active center of formolase to identify key residues for enhanced C1 to C3 bioconversion.

BACKGROUND: Formolase (FLS) is a computationally designed enzyme that catalyzes the carboligation of two or three C1 formaldehyde molecules into C2 glycolaldehyde or C3 dihydroxyacetone (DHA). FLS lays the foundation for several artificial carbon fixation and valorization pathways, such as the artificial starch anabolic pathway. However, the application of FLS is limited by its low catalytic activity and product promiscuity. FINDINGS: FLS, designed and engineered based on benzoylformate decarboxylase from Pseudomonas putida, was selected as a candidate for modification. To evaluate its catalytic activity, 25 residues located within an 8 Å distance from the active center were screened using single-point saturation mutagenesis. A screening approach based on the color reaction of the DHA product was applied to identify the desired FLS variants. After screening approximately 5,000 variants (approximately 200 transformants per site), several amino acid sites that were not identified by directed evolution were found to improve DHA formation. The serine-to-phenylalanine substitution at position 236 improved the activity towards DHA formation by 7.6-fold. Molecular dynamics simulations suggested that the mutation increased local hydrophobicity at the active site, predisposing the cofactor-C2 intermediate to nucleophilic attack by the third formaldehyde molecule for subsequent DHA generation. CONCLUSIONS: This study provides improved FLS variants and valuable information into the influence of residues adjacent to the active center affecting catalytic efficiency, which can guide the rational engineering or directed evolution of FLS to optimize its performance in artificial carbon fixation and valorization.

KIF15 promotes the development and progression of chordoma via activating PI3K-AKT signalling pathway.

Aims: Despite its implication in various human cancers, the expression and functional significance of Kinesin family member 15 (KIF15) in chordomas remain unexplored. Main methods: The evaluation of KIF15 protein levels was conducted through immunohistochemistry (IHC) staining and Western blot analysis. Cell proliferation was quantified using MTT and CCK8 assays, whereas cell migration was examined using wound healing and Transwell assays. Furthermore, flow cytometric analysis was utilized to assess cell apoptosis and the cell cycle. Additionally, in vivo experiments were performed using a mouse xenograft model. Key findings: Our study revealed significantly higher expression of KIF15 in stage III chordoma tissues compared to stage II tissues. Knockdown of KIF15 led to notable inhibition of cell proliferation and migration, along with enhanced apoptosis and cell cycle arrest. In vivo studies further confirmed the inhibitory effects of KIF15 knockdown on chordoma tumour growth. In terms of mechanism, we identified the involvement of the PI3K-AKT signalling pathway mediated by KIF15 in chordomas. Notably, the anti-tumour effects of KIF15 deficiency on chordomas were partially reversed by the addition of an AKT activator. Significance: KIF15 promotes chordoma development and progression through the activation of the PI3K-AKT signalling pathway. Thus, targeting KIF15 might be a promising therapeutic strategy for treating chordomas.

Duration perception in peripheral vision: Underestimation increases with greater stimuli eccentricity.

Duration perception plays a fundamental role in our daily visual activities; however, it can be easily distorted, even in the retinal location. While this topic has been extensively investigated in central vision, similar exploration in peripheral vision is still at an early stage. To investigate the influence of eccentricity, a commonly used indicator for quantifying retinal location, on duration perception in peripheral vision, we conducted two psychophysical experiments. In Experiment 1, we observed that the retinal location influenced the Point of Subjective Equality (PSE) but not the Weber Fraction (WF) of stimuli appearing at eccentricities ranging from 30° to 70°. Except at 30°, the PSEs were significantly longer than 416.7 ms (25 frames), which was the duration of standard stimuli. This suggested that participants underestimated duration, and this underestimation increased with greater distance from the central fixation point on the retina. To eliminate the potential interference of the central task used in Experiment 1, we conducted a supplementary experiment (Experiment 2) that demonstrated that this central task did not change the underestimation (PSE) but did influence the sensitivity (WF) at an eccentricity of 50°. In summary, our findings revealed a compressive effect of eccentricity on duration perception in peripheral vision: as stimuli appeared more peripheral on the retina, there was an increasing underestimation of subjective duration. Reasons and survival advantages of this underestimation are discussed. Findings provide new insight on duration perception in peripheral vision, highlighting an expanding compressive underestimation effect with greater eccentricity.

Development of a growth-coupled selection platform for directed evolution of heme biosynthetic enzymes in Corynebacterium glutamicum.

Heme is an important tetrapyrrole compound, and has been widely applied in food and medicine industries. Although microbial production of heme has been developed with metabolic engineering strategies during the past 20 years, the production levels are relatively low due to the multistep enzymatic processes and complicated regulatory mechanisms of microbes. Previous studies mainly adopted the strategies of strengthening precursor supply and product transportation to engineer microbes for improving heme biosynthesis. Few studies focused on the engineering and screening of efficient enzymes involved in heme biosynthesis. Herein, a growth-coupled, high-throughput selection platform based on the detoxification of Zinc-protoporphyrin IX (an analogue of heme) was developed and applied to directed evolution of coproporphyrin ferrochelatase, catalyzing the insertion of metal ions into porphyrin ring to generate heme or other tetrapyrrole compounds. A mutant with 3.03-fold increase in k cat/K M was selected. Finally, growth-coupled directed evolution of another three key enzymes involved in heme biosynthesis was tested by using this selection platform. The growth-coupled selection platform developed here can be a simple and effective strategy for directed evolution of the enzymes involved in the biosynthesis of heme or other tetrapyrrole compounds.

Directed evolution of a neutrophilic and mesophilic methanol dehydrogenase based on high-throughput and accurate measurement of formaldehyde.

Methanol is a promising one-carbon feedstock for biomanufacturing, which can be sustainably produced from carbon dioxide and natural gas. However, the efficiency of methanol bioconversion is limited by the poor catalytic properties of nicotinamide adenine dinucleotide (NAD+)-dependent methanol dehydrogenase (Mdh) that oxidizes methanol to formaldehyde. Herein, the neutrophilic and mesophilic NAD+-dependent Mdh from Bacillus stearothermophilus DSM 2334 (MdhBs) was subjected to directed evolution for enhancing the catalytic activity. The combination of formaldehyde biosensor and Nash assay allowed high-throughput and accurate measurement of formaldehyde and facilitated efficient selection of desired variants. MdhBs variants with up to 6.5-fold higher Kcat/KM value for methanol were screened from random mutation libraries. The T153 residue that is spatially proximal to the substrate binding pocket has significant influence on enzyme activity. The beneficial T153P mutation changes the interaction network of this residue and breaks the α-helix important for substrate binding into two short α-helices. Reconstructing the interaction network of T153 with surrounding residues may represent a promising strategy to further improve MdhBs, and this study provides an efficient strategy for directed evolution of Mdh.

Nitrogen and sulfur co-doped Ti3C2Tx MXenes for high-rate lithium-ion batteries.

The electrification of heavy-duty transport and aviation urgently requires new strategies to develop high-rate lithium-ion batteries (LIBs) whose performance fundamentally relies on electrode materials. However, commercially available graphite anodes still suffer from slow kinetics of lithium-ion diffusion and severe safety concerns of lithium plating when achieving the high-rate use goal. Herein, taking Ti3C2Tx as an example, it is demonstrated that N and S co-doping in Ti3C2Tx results in a high-rate MXene anode for LIBs. Nitrogen doping not only flattens the MXene layers and expands the interlayer spacing but also increases the Ti valence state change ability. As evidenced by density functional theory calculations, the diffusion barriers of S-containing Ti3C2Tx MXenes are lower than those of the S-free counterpart, suggesting that S plays an essential role in achieving high-rate performance. Therefore, the N and S co-doped Ti3C2Tx anode in LIBs exhibited excellent performance with a reversible capacity of 113.8 mA h g-1 at a rate of 3C and ∼89% capacity retention after 1000 charge/discharge cycles. The high capacity is attributed to the change in the oxidation states of both Ti and O elements, and the tiny volume change within ∼0.6% upon the stable charging/discharging process accounts for the good capacity retention. When paired up with a LiFe0.5Mn0.5PO4 cathode, the full cell delivers a reversible capacity of 134 mA h g-1 after 1000 cycles at a high rate of 1C. The demonstration of N and S co-doped Ti3C2Tx MXenes in this work may offer a feasible approach for high-rate intercalation anode materials.

Decontamination of mustard sulfur and VX by sodium percarbonate complexed with 1-acetylguanidine as a novel activator.

The peroxide-based decontaminants had attracted great attention for degradation of chemical warfare agents (CWAs) because of their high performance, non-corrosive and environmental-friendly merits. Hydrogen peroxide can be activated by some organic activators to enhance the oxidation ability. In this work, a novel formula based on sodium percarbonate (SPC) complexed with 1-acetylguanidine (ACG) was investigated for decontamination of sulfur mustard (HD) and VX as CWAs. In the experimental results, the active species acetyl peroxide imide acid in the formula aqueous solution was detected in situ by Raman and 13C NMR spectroscopy. The optimized conditions of the decontamination formula (SPC/ACG) were suggested that, the molar ratio of active oxygen and activator ([O]/[ACG]) was 1:1 while the pH value of the formula aqueous solution was about 9. To achieve the decontamination percentage over 99%, the molar ratio of active oxygen to CWA ((O)/(CWA)) needed to be at least 3 for HD and 7 for VX. Meanwhile, the degradation products detected by gas chromatography/mass spectrometry (GC/MS), liquid chromatography/mass spectrometry (LC/MS) and ion chromatography (IC) indicated that the oxidation and elimination reactions should have occurred on HD molecule, while the degradation of VX mainly originate from the nucleophilic substitution and oxidation reactions.

Engineering allosteric inhibition of homoserine dehydrogenase by semi-rational saturation mutagenesis screening.

Allosteric regulation by pathway products plays a vital role in amino acid metabolism. Homoserine dehydrogenase (HSD), the key enzyme for the biosynthesis of various aspartate family amino acids, is subject to feedback inhibition by l-threonine and l-isoleucine. The desensitized mutants with the potential for amino acid production remain limited. Herein, a semi-rational approach was proposed to relieve the feedback inhibition. HSD from Corynebacterium glutamicum (CgHSD) was first characterized as a homotetramer, and nine conservative sites at the tetramer interface were selected for saturation mutagenesis by structural simulations and sequence analysis. Then, we established a high-throughput screening (HTS) method based on resistance to l-threonine analog and successfully acquired two dominant mutants (I397V and A384D). Compared with the best-ever reported desensitized mutant G378E, both new mutants qualified the engineered strains with higher production of CgHSD-dependent amino acids. The mutant and wild-type enzymes were purified and assessed in the presence or absence of inhibitors. Both purified mutants maintained >90% activity with 10 mM l-threonine or 25 mM l-isoleucine. Moreover, they showed >50% higher specific activities than G378E without inhibitors. This work provides two competitive alternatives for constructing cell factories of CgHSD-related amino acids and derivatives. Moreover, the proposed approach can be applied to engineering other allosteric enzymes in the amino acid synthesis pathway.

sEMG-Based Continuous Hand Action Prediction by Using Key State Transition and Model Pruning.

Conventional classification of hand motions and continuous joint angle estimation based on sEMG have been widely studied in recent years. The classification task focuses on discrete motion recognition and shows poor real-time performance, while continuous joint angle estimation evaluates the real-time joint angles by the continuity of the limb. Few researchers have investigated continuous hand action prediction based on hand motion continuity. In our study, we propose the key state transition as a condition for continuous hand action prediction and simulate the prediction process using a sliding window with long-term memory. Firstly, the key state modeled by GMM-HMMs is set as the condition. Then, the sliding window is used to dynamically look for the key state transition. The prediction results are given while finding the key state transition. To extend continuous multigesture action prediction, we use model pruning to improve reusability. Eight subjects participated in the experiment, and the results show that the average accuracy of continuous two-hand actions is 97% with a 70 ms time delay, which is better than LSTM (94.15%, 308 ms) and GRU (93.83%, 300 ms). In supplementary experiments with continuous four-hand actions, over 85% prediction accuracy is achieved with an average time delay of 90 ms.

High fraction of soluble trace metals in fine particles under heavy haze in central China.

Atmospheric trace metals are a key component of particulate matter and significantly influence the atmospheric process and human health. The dissolved fraction of trace metals represents their bioavailability and exhibits high chemical activity. However, the optimum measurement method for detecting the soluble fraction of trace metals is still undetermined. The impact of variations in pollution on the soluble fraction is largely unrevealed. Therefore, in this work, a one-month field observation was conducted in Central China and different extraction solvents were used to determine the proper measurement method for the soluble fraction of trace metals and investigate the variation pattern under different pollution conditions. The findings show that solvents with acidity near that of aerosol water can better reflect the actual soluble fraction of trace metals in fine particulate matter. The soluble fraction of trace metals tends to increase with pollution level increased, demonstrating unexpectedly high health risks and chemical activity under heavy haze conditions. Our results indicate that remediation and trace metal pollution control are urgently needed.

Controlled Hydrothermal/Solvothermal Synthesis of High-Performance LiFePO4 for Li-Ion Batteries.

The sluggish Li-ion diffusivity in LiFePO4 , a famous cathode material, relies heavily on the employment of a broad spectrum of modifications to accelerate the slow kinetics, including size and orientation control, coating with electron-conducting layer, aliovalent ion doping, and defect control. These strategies are generally implemented by employing the hydrothermal/solvothermal synthesis, as reflected by the hundreds of publications on hydrothermal/solvothermal synthesis in recent years. However, LiFePO4 is far from the level of controllable preparation, due to the lack of the understanding of the relations between the synthesis condition and the nucleation-and-growth of LiFePO4 . In this paper, the recent progress in controlled hydrothermal/solvothermal synthesis of LiFePO4 is first summarized, before an insight into the relations between the synthesis condition and the nucleation-and-growth of LiFePO4 is obtained. Thereafter, a review over surface decoration, lattice substitution, and defect control is provided. Moreover, new research directions and future trends are also discussed.

[Percutaneous fixation with helical bridge combined fixation system for long split fractures involving the middle and upper humerus].

OBJECTIVE: To evaluate the effectiveness of percutanous fixation with helical bridge combined fixation system (BCFS) for treatment of long split fractures involving the middle and upper humerus. METHODS: Between February 2018 and February 2020, 15 patients of long split fractures involving the middle and upper humerus were treated. There were 6 males and 9 females, with an average age of 62 years (range, 37-82 years). The fractures were caused by slipping in 7 cases, falling from height in 3 cases, and traffic accident in 5 cases. According to AO classification, the shaft fractures were rated as type A in 4 cases, type B in 9 cases, and type C in 2 cases. And all fractures extended to proximal humerus; and the proximal fractures were rated as one-part fracture in 11 cases and two-part fracture in 4 cases according to Neer classification. The interval between injury and operation was 1-7 days (mean, 3.2 days). Nine patients underwent closed reduction and 6 patients underwent open reduction after lengthening the incisions. All fractures were percutaneously internal fixated with helical BCFS after reduction. The operation time, intraoperative blood loss, incision healing, and fracture healing were recorded. Constant-Murley score was used to evaluate shoulder joint function, and Mayo score was used to evaluate elbow joint function. RESULTS: The operation time ranged from 55 to 175 minutes, with an average of 76.5 minutes; the intraoperative blood loss ranged from 80 to 300 mL, with an average of 185.5 mL. All incisions healed by first intention, without infection or radial nerve injury. All patients were followed up 12-23 months, with an average of 16 months. The fractures all reached clinical healing, and the healing time was 12-20 weeks, with an average of 14.5 weeks. At 1 year after operation, the Constant-Murley score of the affected side was 88.7±7.6, and there was no significant difference when compared with that of the healthy side (90.8±8.3) ( t=1.421, P=0.052). According to the elbow Mayo score, the score of the affected side was 97.6±6.5, and there was no significant difference when compared with the healthy side (97.7±7.3) ( t=0.433, P=0.913). CONCLUSION: The helical BCFS can avoid the dissection of deltoid insertion and prevent the iatrogenic radial nerve injury. With satisfied effectiveness, it is suggested for minimally invasive surgical treatment of long split fractures involving the middle and upper humerus.

Understanding charge storage in Nb2CTx MXene as an anode material for lithium ion batteries.

MXenes represent an emerging family of two-dimensional materials of transition metal carbides/carbonitrides terminated with functional groups like -O, -OH, and -F on the chemically active surface of MX slabs. As a member of the family, Nb2CTx exhibits superior lithium storage capacity over most of the other MXenes as anode materials in lithium-ion batteries (LIBs). However, an in-depth understanding of the charge storage mechanism is still lacking so far. Here, through combining complementary experiments and density functional theory calculations, we provide insights into the (de)lithiation process. Specifically, Nb2CTx with dominant -O functional groups stores charge as a result of changes in the oxidation states of both transition metals Nb and O, which is supported by Bader charge analysis showing a significant change in the oxidation states of Nb and O upon lithiation. As monitored by ex situ X-ray diffraction, the interlayer spacing of Nb2CTx changes slightly upon lithium ion (de)intercalation, corresponding to a volume change of only 2.3% with a near zero-strain feature. By coupling with a LiFePO4/C cathode, the full cell presents superior rate capability and cycling stability as well. The insights into the charge storage mechanism of Nb2CTx in this work provide useful guidance for the rational design of MXene-based anode materials for high-performance LIBs.

Zero Lithium Miscibility Gap Enables High-Rate Equimolar Li(Mn,Fe)PO4 Solid Solution.

Forming olivine-structured Li(Mn,Fe)PO4 solid solution is theoretically a feasible way to improve the energy density of the solid solutions for lithium ion batteries. However, the Jahn-Teller active Mn3+ in the solid solution restricts their energy density and rate performance. Here, as demonstrated by operando X-ray diffraction, we show that equimolar LiMn0.5Fe0.5PO4 solid solution nanocrystals undergo a single-phase transition during the whole (de)lithiation process, with a feature of zero lithium miscibility gap, which endows the nanocrystals with excellent electrochemical properties. Specifically, the energy density of LiMn0.5Fe0.5PO4 reaches 625 Wh kg-1, which is 16% higher than that of LiFePO4. Moreover, the high-performance LiMn0.5Fe0.5PO4 nanocrystals are prepared by a microwave-assisted hydrothermal synthesis in pure water.

Knockdown of TMED3 inhibits cell viability and migration and increases apoptosis in human chordoma cells.

Chordoma is a rare low­grade tumor of the axial skeleton. Over previous decades, a range of targeted drugs have been used for treating chordoma, with more specific and effective therapies under investigation. Transmembrane Emp24 protein transport domain containing 3 (TMED3) is a novel gene reported to be a regulator of oncogenesis, cancer development and metastasis; however, its role in chordoma remains unclear. In the present study, the expression of TMED3 was investigated in chordoma cells, and the effect of TMED3 knockdown on chordoma development was examined in vitro and in vivo, followed by exploration of differentially expressed proteins in TMED3­silenced chordoma cells via an apoptosis antibody array. Reverse transcription­quantitative PCR and western blot assays were performed to determine the expression levels. It was revealed that TMED3 was highly expressed in chordoma, and that knockdown of TMED3 inhibited cell viability and migration, and enhanced the apoptosis of chordoma cells. Additionally, knockdown of TMED3 inhibited the expression of Bcl­2, heat shock protein 27, insulin­like growth factor (IGF)­I, IGF­II, IGF binding protein­2, Livin, Akt, CDK6 and cyclin D1 proteins, whereas MAPK9 was upregulated. Furthermore, a xenograft nude mice model demonstrated that TMED3 expression promoted tumor growth. Collectively, the present findings suggested that knockdown of TMED3 inhibited cell viability and migration, and enhanced apoptosis in chordoma cells, and that TMED3 may be a novel target for chordoma therapy.

Unique chemical activity in porous YbB2C2 ceramics with high porosity and high compressive strength.

High purity layered YbB2C2 powder is synthesized by a boro/carbothermic reduction method using YbBO3, B4C and graphite powders as raw materials. Its X-ray diffraction data are presented, and the space group P4/mbm (No. 127) is confirmed. The lattice parameters are a = b = 5.3389 Å and c = 3.5683 Å, and the atom positions are Yb (0.0000, 0.0000, 0.0000), B (0.3621, 0.8621, 0.5000), and C (0.1606, 0.6606, 0.5000). Porous YbB2C2 ceramics have a high porosity in the range of 69.89-58.11% and a high compressive strength in the range of 19.49-63.44 MPa. Furthermore, the as-produced porous YbB2C2 ceramics show unique chemical activity. Porous YbB2C2 ceramic with a porosity of 69.89% emits so much heat that it can burn a piece of paper when this ceramic is wetted by water. The rate of reaction between the porous YbB2C2 ceramic and water can be simply controlled by adjusting the porosity. The solid reaction products are YbB6, C and an unknown amorphous phase.

Seasonal characterization of aerosol composition and sources in a polluted city in Central China.

We characterized the aerosol composition and sources of particulate matter (PM) in Sanmenxia, a polluted city located in the Fen-Wei Plain region of Central China. The PM2.5 concentration decreased by 18% from 72 µg m-3 in 2014 to 59 µg m-3 in 2019. All chemical species presented pronounced seasonal variations, with their highest concentrations in winter due to enhanced emissions and the frequent stagnant meteorological conditions. Nitrate was the major fraction of PM2.5 during all seasons (35-41%) except summer (25%), while sulfate was a dominant species in summer (29%) compared to other seasons (16-18%) from July 2018 to June 2019. The detailed analysis of a wintertime severe haze episode that lasted for approximately half a month demonstrated that secondary aerosols, including secondary organic aerosol, sulfate, nitrate, and ammonium, contributed 89% to non-refractory PM1 (NR-PM1), indicating the remarkable role of secondary aerosol formation in air pollution in Sanmenxia. Positive matrix factorization analysis further showed considerably enhanced low-volatility oxygenated organic aerosol (OA) and hydrocarbon-like OA during severe haze episodes, while significant contributions in semi-volatile oxygenated OA and coal combustion OA during clean periods. Severe pollution events in the city were generally associated with air masses from the southwest, and we also found that aerosol species, especially secondary aerosol species, showed distinct forenoon increases that were caused by the subsidence of air pollutants aloft. Our results highlight that future air quality improvement would benefit substantially from a more efficient control of gaseous precursors, particularly the NOx emissions from industry and vehicle emissions.