Two "turn on" fluorescence probes based on nitroso recognition group for detecting hydrogen sulfide.

Hydrogen sulfide is a vital signaling molecule which holds a pivotal position in numerous biological functions. In this research, two novel "OFF-ON" fluorescence probes named YNO and TNO were designed based on the nitroso recognition group to detect H2S. Both YNO and TNO performed outstanding response rate and linear relationship between the fluorescence intensity and the concentration of H2S. YNO possessed larger Stokes shift and longer emission wavelength. TNO had lower limit of detection. In addition, YNO was successful applied to sense endogenous and exogenous H2S and target endoplasmic reticulum (ER) in Hela cells.

Biomechanical study of spinal cord and nerve root in idiopathic scoliosis: based on finite element analysis.

BACKGROUND: Current research lacks comprehensive investigation into the biomechanical changes in the spinal cord and nerve roots during scoliosis correction. This study employs finite element analysis to extensively explore these biomechanical variations across different Cobb angles, providing valuable insights for clinical treatment. METHODS: A personalized finite element model, incorporating vertebrae, ligaments, spinal cord, and nerve roots, was constructed using engineering software. Forces and displacements were applied to achieve Cobb angle improvements, designating T1/2-T4/5 as the upper segment, T5/6-T8/9 as the middle segment, and T9/10-L1/2 as the lower segment. Simulations under traction, pushing, and traction + torsion conditions were conducted, and biomechanical changes in each spinal cord segment and nerve roots were analyzed. RESULTS: Throughout the scoliosis correction process, the middle spinal cord segment consistently exhibited a risk of injury under various conditions and displacements. The lower spinal cord segment showed no significant injury changes under traction + torsion conditions. In the early correction phase, the upper spinal cord segment demonstrated a risk of injury under all conditions, and the lower spinal cord segment presented a risk of injury under pushing conditions. Traction conditions posed a risk of nerve injury on both sides in the middle and lower segments. Under pushing conditions, there was a risk of nerve injury on both sides in all segments. Traction + torsion conditions implicated a risk of injury to the right nerves in the upper segment, both sides in the middle segment, and the left side in the lower segment. In the later correction stage, there was a risk of injury to the upper spinal cord segment under traction + torsion conditions, the left nerves in the middle segment under traction conditions, and the right nerves in the upper segment under pushing conditions. CONCLUSION: When the correction rate reaches 61-68%, particular attention should be given to the upper-mid spinal cord. Pushing conditions also warrant attention to the lower spinal cord and the nerve roots on both sides of the main thoracic curve. Traction conditions require attention to nerve roots bilaterally in the middle and lower segments, while traction combined with torsion conditions necessitate focus on the right-side nerve roots in the upper segment, both sides in the middle segment, and the left-side nerve roots in the lower segment.

Biomechanical Effects of Different Prosthesis Types and Fixation Ranges in Multisegmental Total En Bloc Spondylectomy: A Finite Element Study.

OBJECTIVE: Multi-segmental total en bloc spondylectomy (TES) gradually became more commonly used by clinicians. However, the choice of surgical strategy is unclear. This study aims to investigate the biomechanical performance of different prosthesis types and fixation ranges in multisegmental TES. METHODS: In this study, a validated finite element model of T12-L2 post-spondylectomy operations were carried out. The prostheses of these models used either 3D-printed artificial vertebrae or titanium mesh cages. The fixed range was two or three segment levels. Range of motion, stress distribution of the endplate and internal fixation system, intervertebral disc pressure, and facet joint surface force of four postoperative models and intact model in flexion and extension, as well as lateral bending and rotation were analyzed and compared. RESULTS: The type of prosthesis used in the anterior column reconstruction mainly affected the stress of the adjacent endplate and the prosthesis itself. The posterior fixation range had a greater influence on the overall range of motion (ROM), the ROM of the adjacent segment, the stress of the screw-rod system, and adjacent facet joint surface force. For the model of the same prosthesis, the increase of fixed length resulted in an obvious reduction of ROM. The maximal decrease was 70.23% during extension, and the minimal decrease was 30.19% during rotation. CONCLUSION: In three-segment TES, the surgical strategy of using 3D-printed artificial prosthesis for anterior column support and pedicle screws for posterior fixation at both two upper and lower levels respectively can reduce the stress on internal fixation system, endplates, and adjacent intervertebral discs, resulting in a reduced risk of internal fixation failure, and ASD development.

Onametostat, a PfPRMT5 inhibitor, exhibits antimalarial activity to Plasmodium falciparum.

Protein arginine methyltransferases (PRMTs) play critical roles in Plasmodium falciparum, a protozoan causing the deadliest form of malaria, making them potential targets for novel antimalarial drugs. Here, we screened 11 novel PRMT inhibitors against P. falciparum asexual growth and found that onametostat, an inhibitor for type II PRMTs, exhibited strong antimalarial activity with a half-maximal inhibitory concentration (IC50) value of 1.69 ± 0.04 µM. In vitro methyltransferase activities of purified PfPRMT5 were inhibited by onametostat, and a shift of IC50 to onametostat was found in the PfPRTM5 disruptant parasite line, indicating that PfPRTM5 is the primary target of onametostat. Consistent with the function of PfPRMT5 in mediating symmetric dimethylation of histone H3R2 (H3R2me2s) and in regulating invasion-related genes, onametostat treatment led to the reduction of H3R2me2s level in P. falciparum and caused the defects on the parasite's invasion of red blood cells. This study provides a starting point for identifying specific PRMT inhibitors with the potential to serve as novel antimalarial drugs.

Covalent Organic Framework Membranes with Patterned High-Density Through-Pores for Ultrafast Molecular Sieving.

The creation of uniformly molecular-sized through-pores within polymeric membranes and the direct evidence of these pores are essential for fundamentally understanding the transport mechanism and improving separation efficiency. Herein, we report an electric-field-assisted interface synthesis approach to fabricating large-area covalent organic framework (COF) membranes that consist of preferentially oriented single-crystalline COF domains. These single-crystalline frameworks were translated into high-density, vertically aligned through-pores across the entire membrane, enabling the direct visualization of membrane pores with an ultrahigh resolution of 2 Å using the low-dose high-resolution transmission electron microscopy technique (HRTEM). The density of directly visualized through-pores was quantified to be 1.2 × 1017 m-2, approaching theoretical predictions. These COF membranes demonstrate ultrahigh solvent permeability, which is 10 times higher than that of state-of-the-art organic solvent nanofiltration membranes. When applied to high-value pharmaceutical separations, their COF membranes exhibit 2 orders of magnitude higher methanol permeance and 20-fold greater enrichment efficiency than their commercial counterparts.

Novel fluorescence probe for ClO- in living cells: Based on FRET mechanism.

Hypochlorous acid (HClO) as a kind of reactive oxygen species (ROS) plays a vital role in many biological processes. Organic fluorescence probes have attracted great interests for the detection of HClO, due to their relatively high selectivity and sensitivity, satisfactory spatiotemporal resolution and good biocompatibility. Constructing fluorescence probes to detect HClO with advantages of large Stokes shift, wide emission gap, near infrared emission and good water solubility is still challenging. In this work, a new ratiometric fluorescence probe (named HCY) for HClO was developed. FRET-based HCY was constructed by bonding a coumarin and a flavone fluorophore. In absence of HClO, HCY exists FRET process, however, FRET is inhibited in the presence of HClO because the conjugated double bond broke. Due to the good match of the emission spectrum of the donor and the absorption spectrum of the acceptor, the FRET system appears favorable energy transfer efficiency. HCY showed high sensitivity and rapid response time. The linearity between the ratios of fluorescence intensity and concentration of HClO was established with a low limit of detection. What's more, HCY was also applied for fluorescence images of HClO in RAW264.7 cells.

Colossal Zero-Field-Cooled Exchange Bias via Tuning Compensated Ferrimagnetic in Kagome Metals.

Exchange bias (EB) is a crucial property with widespread applications but particularly occurs by complex interfacial magnetic interactions after field cooling. To date, intrinsic zero-field-cooled EB (ZEB) has only emerged in a few bulk frustrated systems and their magnitudes remain small yet. Here, enabled by high temperature synthesis, we uncover a colossal ZEB field of 4.95 kOe via tuning compensated ferrimagnetism in a family of kagome metals, which is almost twice the magnitude of known materials. Atomic-scale structure, spin dynamics, and magnetic theory revealed that these compensated ferrimagnets originate from significant antiferromagnetic exchange interactions embedded in the holmium-iron ferrimagnetic matrix due to supersaturated preferential manganese doping. A random antiferromagnetic order of manganese sublattice sandwiched between ferromagnetic iron kagome bilayers accounts for such unconventional pinning. The outcome of the present study outlines disorder-induced giant bulk ZEB and coercivity in layered frustrated systems.

Stereointerface Structure Drives Ferroelectricity in BaZrO3 Films.

Interfacial strain engineering can induce structural transformation and introduce new physical properties into materials, which is an effective method to prepare new multifunctional materials. However, interfacial strain has a limited spatial impact size. For example, in 2D thin films, the critical thickness of biaxial strain is typically less than 20 nm, which is not conducive to the maintenance of a strained structure and properties in thick film materials. The construction of a 3D interface can solve this problem. The large lattice mismatch between the BaZrO3 thin film and the substrate can induce the out-of-phase boundary (OPB) structure, which can extend along the thickness direction with the stacking of atoms. The lattice distortion at the OPB structure can provide a clamping effect for each layer of atoms, thus expanding the spatial influence range of biaxial strain. As a result, the uniform in-plane strain distribution and strain-induced ferroelectricity (Pr = 13 µC/cm2) are maintained along the thickness direction in BaZrO3 films.

Intrinsic-strain-induced ferroelectric order and ultrafine nanodomains in SrTiO3.

Nano ferroelectrics holds the potential application promise in information storage, electro-mechanical transformation, and novel catalysts but encounters a huge challenge of size limitation and manufacture complexity on the creation of long-range ferroelectric ordering. Herein, as an incipient ferroelectric, nanosized SrTiO3 was indued with polarized ordering at room temperature from the nonpolar cubic structure, driven by the intrinsic three-dimensional (3D) tensile strain. The ferroelectric behavior can be confirmed by piezoelectric force microscopy and the ferroelectric TO1 soft mode was verified with the temperature stability to 500 K. Its structural origin comes from the off-center shift of Ti atom to oxygen octahedron and forms the ultrafine head-to-tail connected 90° nanodomains about 2 to 3 nm, resulting in an overall spontaneous polarization toward the short edges of nanoparticles. According to the density functional theory calculations and phase-field simulations, the 3D strain-related dipole displacement transformed from [001] to [111] and segmentation effect on the ferroelectric domain were further proved. The topological ferroelectric order induced by intrinsic 3D tensile strain shows a unique approach to get over the nanosized limitation in nanodevices and construct the strong strain-polarization coupling, paving the way for the design of high-performance and free-assembled ferroelectric devices.

The postoperative clinical effects of utilizing 3D printed (Ti6Al4V) interbody fusion cages in posterior lumbar fusion: A retrospective cohort study.

BACKGROUND: The research focused on the postoperative effect of using interbody fusion cage in lumbar posterior lamina decompression and interbody fusion with pedicle screw by comparing the postoperative effect of using 3D printing (Ti6Al4V) and PEEK material interbody fusion cage. METHODS: Ninety-one patients with lumbar degenerative diseases from the Department of Spine Surgery of Tianjin Hospital were included in the study cohort. They were divided into 3D group (n = 39) and PEEK group (n = 52) according to the use of interbody fusion cage. The imaging data of the patients were collected and the postoperative data of the 2 groups were compared to evaluate patients' health status and the recovery of lumbar structure and function after operation. RESULTS: Combined with the degree of fusion, the clinical effect of 3D printing titanium alloy interbody fusion cage was comprehensively judged. At the last follow-up, the JOA score, ODI index, VAS, prolo function score, and SF-36 scale of the 2 groups showed that the clinical symptoms were better than those before operation (P < .05). The height of intervertebral disc, the area of intervertebral foramen and the physiological curvature of lumbar vertebrae increased in varying degrees after operation (P < .05). At the last follow-up, the vertebral cage fusion rates were as high as 89.13% and 90.91% in the 3D and PEEK groups, with collapse rates of 6.5% and 4.5%, respectively. There were 10 cases of cage displacement in 3D group and 7 cases of cage displacement in PEEK group. There was no significant difference between the 2 groups (P > .05). CONCLUSIONS: In conclusion, 3D printed (Ti6Al4V) interbody fusion cage can obtain good clinical effect in the surgical treatment of lumbar degenerative diseases. Posterior lumbar lamina decompression, bilateral pedicle screw fixation combined with 3D printed cage interbody fusion is excellent in rebuilding the stability of lumbar vertebrae. 3D printed interbody fusion cage can be an ideal substitute material for intervertebral bone grafting. The stable fusion time of interbody fusion cage after lumbar fusion is mostly from 3 months to half a year after operation.

Identification of shared gene signatures and pathways for diagnosing osteoporosis with sarcopenia through integrated bioinformatics analysis and machine learning.

BACKGROUND: Prior studies have suggested a potential relationship between osteoporosis and sarcopenia, both of which can present symptoms of compromised mobility. Additionally, fractures among the elderly are often considered a common outcome of both conditions. There is a strong correlation between fractures in the elderly population, decreased muscle mass, weakened muscle strength, heightened risk of falls, and diminished bone density. This study aimed to pinpoint crucial diagnostic candidate genes for osteoporosis patients with concomitant sarcopenia. METHODS: Two osteoporosis datasets and one sarcopenia dataset were obtained from the Gene Expression Omnibus (GEO). Differential expression genes (DEGs) and module genes were identified using Limma and Weighted Gene Co-expression Network Analysis (WGCNA), followed by functional enrichment analysis, construction of protein-protein interaction (PPI) networks, and application of a machine learning algorithm (least absolute shrinkage and selection operator (LASSO) regression) to determine candidate hub genes for diagnosing osteoporosis combined with sarcopenia. Receiver operating characteristic (ROC) curves and column line plots were generated. RESULTS: The merged osteoporosis dataset comprised 2067 DEGs, with 424 module genes filtered in sarcopenia. The intersection of DEGs between osteoporosis and sarcopenia module genes consisted of 60 genes, primarily enriched in viral infection. Through construction of the PPI network, 30 node genes were filtered, and after machine learning, 7 candidate hub genes were selected for column line plot construction and diagnostic value assessment. Both the column line plots and all 7 candidate hub genes exhibited high diagnostic value (area under the curve ranging from 1.00 to 0.93). CONCLUSION: We identified 7 candidate hub genes (PDP1, ALS2CL, VLDLR, PLEKHA6, PPP1CB, MOSPD2, METTL9) and constructed column line plots for osteoporosis combined with sarcopenia. This study provides reference for potential peripheral blood diagnostic candidate genes for sarcopenia in osteoporosis patients.

Unraveling the Intertwining Factors Underlying the Assembly of High-Nuclearity Heterometallic Clusters.

Two closely related yet distinctly different cationic clusters, [Dy52Ni44(HEIDA)36(OH)138(OAc)24(H2O)30]10+ (1) and [Dy112Ni76(HEIDA)44(EIDA)24(IDA)4(OH)268(OAc)48(H2O)44]4+ (2) (HEIDA=N-(2-hydroxyethyl)iminodiacetate), each featuring a multi-shell core of Platonic and Archimedean polyhedra, were obtained. Depending on the specific conditions used for the co-hydrolysis of Dy3+ and Ni2+, the product can be crystallized out as one particular type of cluster or as a mixture of 1 and 2. How the reaction process was affected by the amount of hydrolysis-facilitating base and/or by the reaction temperature and duration was investigated. It has been found that a reaction at a high temperature and/or for an extended period favors the formation of the compact and thermodynamically more stable 1, while a brief reaction with a large amount of the base is good for the kinetic product 2. By tuning these intertwining conditions, the reaction can be regulated toward a particular product.

Biomechanical Comparison of Different Surgical Strategies for Skip-level Cervical Degenerative Disc Disease: A Finite Element Study.

STUDY DESIGN: We constructed finite element (FE) models of the cervical spine consisting of C2-C7 and predicted the biomechanical effects of different surgical procedures and instruments on adjacent segments, internal fixation systems, and the overall cervical spine through FE analysis. OBJECTIVE: To compare the biomechanical effects between the zero-profile device and cage-plate device in skip-level multistage anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: ACDF is often considered the standard treatment for degenerative cervical spondylosis. However, the selection of surgical methods and instruments in cases of skip-level cervical degenerative disk disease is still controversial. MATERIALS AND METHODS: Three FE models were constructed, which used noncontiguous 2-level Zero-P (NCZP) devices for C3/4 and C5/6, a noncontiguous 2-level cage-plate (NCCP) for C3/4 and C5/6, and a contiguous 3-level cage-plate (CCP) for C3/6. Simulate daily activities in ABAQUS. The range of motion (ROM), von Mises stress distribution of the endplate and internal fixation system, and intervertebral disk pressure (IDP) of each model were recorded and compared. RESULTS: Similar to the stress of the cortical bone, the maximum stress of the Zero-P device was higher than that of the CP device for most activities. The ROM increments of the superior, inferior, and intermediate segments of the NCZP model were lower than those of the NCCP and CCP models in many actions. In terms of the IDP, the increment value of stress for the NCZP model was the smallest, whereas those of the NCCP and CCP models were larger. Similarly, the increment value of stress on the endplate also shows the minimum in the NCZP model. CONCLUSIONS: Noncontiguous ACDF with zero profile can reduce the stress on adjacent intervertebral disks and endplates, resulting in a reduced risk of adjacent segment disease development. However, the high cortical bone stress caused by the Zero-P device may influence the risk of fractures.

Decoding Active Sites for Highly Efficient Semihydrogenation of Acetylene in Palladium-Copper Nanoalloys.

Accurately decoding the three-dimensional atomic structure of surface active sites is essential yet challenging for a rational catalyst design. Here, we used comprehensive techniques combining the pair distribution function and reverse Monte Carlo simulation to reveal the surficial distribution of Pd active sites and adjacent coordination environment in palladium-copper nanoalloys. After the fine-tuning of the atomic arrangement, excellent catalytic performance with 98% ethylene selectivity at complete acetylene conversion was obtained in the Pd34Cu66 nanocatalysts, outperforming most of the reported advanced catalysts. The quantitative deciphering shows a large number of active sites with a Pd-Pd coordination number of 3 distributed on the surface of Pd34Cu66 nanoalloys, which play a decisive role in highly efficient semihydrogenation. This finding not only opens the way for guiding the precise design of bimetal nanocatalysts from atomic-level insight but also provides a method to resolve the spatial structure of active sites.

The DEAD-box RNA helicase PfDOZI imposes opposing actions on RNA metabolism in Plasmodium falciparum.

In malaria parasites, the regulation of mRNA translation, storage and degradation during development and life-stage transitions remains largely unknown. Here, we functionally characterized the DEAD-box RNA helicase PfDOZI in P. falciparum. Disruption of pfdozi enhanced asexual proliferation but reduced sexual commitment and impaired gametocyte development. By quantitative transcriptomics, we show that PfDOZI is involved in the regulation of invasion-related genes and sexual stage-specific genes during different developmental stages. PfDOZI predominantly participates in processing body-like mRNPs in schizonts but germ cell granule-like mRNPs in gametocytes to impose opposing actions of degradation and protection on different mRNA targets. We further show the formation of stress granule-like mRNPs during nutritional deprivation, highlighting an essential role of PfDOZI-associated mRNPs in stress response. We demonstrate that PfDOZI participates in distinct mRNPs to maintain mRNA homeostasis in response to life-stage transition and environmental changes by differentially executing post-transcriptional regulation on the target mRNAs.

The effects of acteoside on locomotor recovery after spinal cord injury - The role of autophagy and apoptosis signaling pathway.

In the current study, we investigated the effects of acteoside as a phenylpropanoid glycoside on interaction with neurons to assesses locomotor recovery after spinal cord injury (SCI) in rats by focusing on evaluating the factors involved in autophagy, apoptosis, inflammation and oxidative stress processes. 49 Spargue-Dawley rats were prepared and divided into seven healthy and SCI groups receiving different concentrations of acteoside. After 28 days of disease induction and treatment with acteoside, a BBB score test was used to evaluate locomotor activity. Then, by preparing spinal cord cell homogenates, the expression levels of MAP1LC3A, MAP-2, glial fibrillary acidic protein (GFAP), Nrf2, Keap-1, Caspase 3 (Casp3), Bax, Bcl-2, TNF-a, IL-1B, reactive oxygen species (ROS), and malondialdehyde (MDA) were measured. Improvement of locomotor activity in SCI rats receiving acteoside was observed two weeks after the beginning of the experiment and continued until the fourth week. Both MAP1LC3A and MAP-2 were significantly up-regulated in SCI rats treated with acteoside compared to untreated SCI rats, and GFAP levels were significantly decreased in these animals. Pro-apoptotic proteins Bax and Casp3 and anti-apoptotic protein Bcl-2 were down-regulated and up-regulated, respectively, in SCI rats receiving acteoside. In addition, a significant downregulation of iNOS, TNF-α, and IL-1ß and a decrease in contents of both ROS and MDA as well as increases in Nrf2 and Keap-1 were seen in rats receiving acteoside. Furthermore, acteoside strongly interacted with MAP1LC3A, TNF-α, and Casp3 targets with binding affinities of -8.3 kcal/mol, -8.3 kcal/mol, and -8.5 kcal/mol, respectively, determined by molecular docking studies. In general, it can be concluded that acteoside has protective effects in SCI and can be considered as an adjuvant therapy in the treatment of this disease. However, more studies, especially clinical studies, are needed in this field.

In vivo axial load-share ratio measurement using a novel hexapod system for safe external fixator removal.

BACKGROUND: External fixation is widely used in the treatment of traumatic fractures; however, orthopedic surgeons encounter challenges in deciding the optimal time for fixator removal. The axial load-share ratio (LS) of the fixator is a quantitative index to evaluate the stiffness of callus healing. This paper introduces an innovative method for measuring the LS and assesses the method's feasibility and efficacy. Based on a novel hexapod LS-measurement system, the proposed method is to improve the convenience and precision of measuring LS in vivo, hence facilitating the safe removal of external fixators. METHODS: A novel hexapod system is introduced, including its composition, theoretical model, and method for LS measurement. We conducted a retrospective study on 82 patients with tibial fractures treated by the Taylor Spatial Frame in our hospital from September 2018 to June 2020, of which 35 took LS measurements with our novel method (Group I), and 47 were with the traditional method (Group II). The external fixator was removed when the measurement outcome (LS < 10%) was consistent with the surgeon's diagnosis based on the clinical and radiological assessment (bone union achieved). RESULTS: No significant difference was found in the fracture healing time (mean 25.3 weeks vs. 24.9 weeks, P > 0.05), frame-wearing duration (mean 25.5 weeks vs. 25.8 weeks, P > 0.05), or LS measurement frequency (mean 1.1 times vs. 1.2 times, P > 0.05). The measurement system installation time in Group I was significantly shorter compared to Group II (mean 14.8 min vs. 81.3 min, P < 0.001). The LS value of the first measurement in Group I was lower than that of Group II (mean 5.1% vs. 6.9%, P = 0.011). In Group I, the refracture rate was 0, but in Group II it was 4.3% (2/47, P > 0.05). CONCLUSION: The novel hexapod LS-measurement system and involved method demonstrated enhanced convenience and precision in measuring the LS of the external fixator in vivo. The LS measurement indicates the callus stiffness of fracture healing, and is applicable to evaluate the safety of removing the fixator. Consequently, it is highly recommended for widespread adoption in clinical practice.

The role of the paraspinal muscles in the development of adolescent idiopathic scoliosis based on surface electromyography and radiographic analysis.

BACKGROUND: Patients with idiopathic scoliosis commonly present with an imbalance of the paraspinal muscles. However, it is unclear whether this muscle imbalance is an underlying cause or a result of idiopathic scoliosis. This study aimed to investigate the role of paraspinal muscles in the development of idiopathic scoliosis based on surface electromyography (sEMG) and radiographic analyses. METHODS: This was a single-center prospective study of 27 patients with single-curve idiopathic scoliosis. Posteroanterior whole-spine radiographs and sEMG activity of the erector spinae muscles were obtained for all patients in the habitual standing position (HSP), relaxed prone position (RPP), and prone extension position (PEP). The Cobb angle, symmetrical index (SI) of the sEMG activity (convex/concave), and correlation between the two factors were analyzed. RESULTS: In the total cohort, the mean Cobb angle in the HSP was significantly greater than the mean Cobb angle in the RPP (RPP-Cobb) (p < 0.001), whereas the mean Cobb angle in the PEP (PEP-Cobb) did not differ from the RPP-Cobb. Thirteen patients had a PEP-Cobb that was significantly smaller than their RPP-Cobb (p = 0.007), while 14 patients had a PEP-Cobb that was significantly larger than their RPP-Cobb (p < 0.001). In the total cohort and two subgroups, the SI of sEMG activity at the apex vertebra (AVSI) in the PEP was significantly greater than 1, revealing significant asymmetry, and was also significantly larger than the AVSI in the RPP. In the RPP, the AVSI was close to 1 in the total cohort and two subgroups, revealing no significant asymmetry. CONCLUSION: The coronal Cobb angle and the SI of paraspinal muscle activity in AIS patients vary with posture changes. Asymmetrical sEMG activity of the paraspinal muscles may be not an inherent feature of AIS patients, but is evident in the challenging tasks. The potential significance of asymmetric paraspinal muscle activity need to be explored in further research.

Transforming the CRISPR/dCas9-based gene regulation technique into a forward screening tool in Plasmodium falciparum.

It is a significant challenge to assess the functions of many uncharacterized genes in human malaria parasites. Here, we present a genetic screening tool to assess the contribution of essential genes from Plasmodium falciparum by the conditional CRISPR-/deadCas9-based interference and activation (i/a) systems. We screened both CRISPRi and CRISPRa sets, consisting of nine parasite lines per set targeting nine genes via their respective gRNAs. By conducting amplicon sequencing of gRNA loci, we identified the contribution of each targeted gene to parasite fitness upon drug (artemisinin, chloroquine) and stress (starvation, heat shock) treatment. The screening was highly reproducible, and the screening libraries were easily generated by transfection of mixed plasmids expressing different gRNAs. We demonstrated that this screening is straightforward, robust, and can provide a fast and efficient tool to study essential genes that have long presented a bottleneck in assessing their functions using existing genetic tools.