Human head-neck model and its application thresholds: a narrative review.

There had been many studies on human head-neck biomechanical models in the last two decades, and the associated modelling techniques were constantly evolving at the same time. Computational approaches had been widely leveraged, in parallel to conventional physical tests, to investigate biomechanics and injuries of the head-neck system in the fields like automotive industry, orthopaedic, sports medicine, etc. The purpose of this manuscript is to provide a global review of the existing knowledge related to the modelling approaches, structural and biomechanical characteristics, validation and application of the present head-neck models. This endeavor aims to support further enhancements and validations in modeling practices, particularly addressing the lack of data for model validation, as well as to prospect the future advances in terms of the topics. Seventy-four models subject to the proposed selection criteria are considered. Based on previously established and validated head-neck computational models, most of the studies performed in-depth investigations of included cases, which revolved around four specific subjects: physio-pathology, treatment evaluation, collision condition, and sports injury. Through the review of the recent 20 years research, the summarized modeling information indicated existing deficiencies and future research topics, as well as provided references for subsequent head-neck model development and application.

Phosphorus immobilization in sulfide-ferrous oxidation process driven by nitrate reduction during black-odorous sediment remediation.

During remediation of black-odorous sediment, the pathways of phosphorus immobilization require clarification alongside the oxidation of sulfide and ferrous. This study separated the oxidation stages of sulfide and ferrous through controlled sodium nitrate dosing ratios and methods, and analyzed the changes in phosphorus species and immobilization effects throughout these processes. Results showed that iron-bound phosphorus was the primary contributor to the phosphorus immobilization in the oxidation process, with increased 19% in ferrous oxidation stage and affected the transformation between phosphorus sources or sinks in the adsorption experiment. Additionally, the increase in abundance of phosphorus uptake and transport genes, and denitrifying phosphorus accumulation genes in sediment after ferrous oxidation (1 %-18 % and 87 %-164 %, respectively) indicated the potential for biological phosphorus immobilization. These results demonstrated that higher degrees of sediment oxidation correlate with stronger phosphorus immobilization capacities, providing theoretical bases for phosphorus immobilization during the restoration of black-odorous water bodies.

Recent advances of multifunctional zwitterionic polymers for biomedical application.

Zwitterionic polymers possess equal total positive and negative charges in the repeating units, making them electrically neutral overall. This unique property results in superhydrophilicity, which makes the zwitterionic polymers highly effective in resisting protein adsorption, thus endowing the drug carriers with long blood circulation time, inhibiting thrombus formation on biomedical devices in contact with blood, and ensuring the good sensitivity of sensors in biomedical application. Moreover, zwitterionic polymers have tumor-targeting ability and pH-responsiveness, rendering them ideal candidates for antitumor drug delivery. Additionally, the high ionic conductivity of zwitterionic polymers makes them an important raw material for ionic skin. Zwitterionic polymers exhibit remarkable resistance to bacterial adsorption and growth, proving their suitability in a wide range of biomedical applications such as ophthalmic applications, and wound dressings. In this paper, we provide an in-depth analysis of the different structures and characteristics of zwitterionic polymers and highlight their unique qualities and suitability for biomedical applications. Furthermore, we discuss the limitations and challenges that must be overcome to realize the full potential of zwitterionic polymers and present an optimistic perspective for zwitterionic polymers in the biomedical fields. STATEMENT OF SIGNIFICANCE: Zwitterionic polymers have a series of excellent properties such as super hydrophilicity, anti-protein adsorption, antibacterial ability and good ionic conductivity. However, biomedical applications of multifunctional zwitterionic polymers are still a major field to be explored. This review focuses on the design and application of zwitterionic polymers-based nanosystems for targeted and responsive delivery of antitumor drugs and cancer diagnostic agents. Moreover, the use of zwitterionic polymers in various biomedical applications such as biomedical devices in contact with blood, biosensors, ionic skin, ophthalmic applications and wound dressings is comprehensively described. We discuss current results and future challenges for a better understanding of multifunctional zwitterionic polymers for biomedical applications.

Piped-slow-release calcium nitrate dosing: A new approach to in-situ sediment odor control in rural areas.

Calcium nitrate addition is economically viable and highly efficient for the in-situ treatment of contaminated sediment and enhancement of surface water quality, particularly in rural areas. However, conventional nitrate addition technologies have disadvantages such as excessive nitrate release, sharp ammonium increase, and weakened sulfide oxidation efficiency owing to rapid nitrate injection into the sediment. To resolve these defects, we propose a piped-slow-release (PSR) calcium nitrate dosing method and investigate its treatment efficiency and underlying mechanisms. The results illustrated that PSR dosing had a longer half-life (t1/2 = 5.08 days) and a lower maximum apparent nitrate escape rate of 1.28 % than conventional nitrate injection and other dosing methods. In addition, the PSR managed the inorganic nitrogen release into the overlying water, and after the treatment, the nitrate, ammonium, and nitrite concentrations of 0 mg/L, 8.60 mg/L, and 0 mg/L on day 28 were close to those of the control group (0 mg/L, 8.76 mg/L, and 0 mg/L, respectively). Moreover, the PSR method maintained a moderate nitrate concentration of approximately 3000 mg/L in sediment interstitial water by its controlled-release design, thus greatly enhancing the sulfide oxidation efficiency by relieving the inhibitory effects of high nitrate concentrations, with 83.0 % sulfide being eradicated within 5 days. Sulfide-ferrous nitrate reduction (denitrification and dissimilatory nitrate reduction to ammonium) genera (e.g., Sulfurimonas, Thiobacillus, and Thioalkalispira) were successively enhanced and dominated the microbial community, and the related functional genes displayed high relative abundances. These results imply that the PSR dosing method for calcium nitrate, characterized by flexible operation, high efficiency, low cost, and controllable processes, is appropriate for remediating black-odorous sediment in rural areas.

Impact of smoking cessation duration on lung cancer mortality: A systematic review and meta-analysis.

BACKGROUND: Smoking history is a heterogeneous situation for different populations, and numerous studies suggest that smoking cessation is conducive to reduce the mortality of lung cancer. However, no quantitative meta-analysis regarding smoking cessation duration based on different populations has demonstrated it clearly. METHODS: We systematically searched four electronic databases (PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Scoups) till February 2023. Eligible studies reported the association between lung cancer survival and duration of smoking cessation. Additionally, we stratified the study population according to whether they had lung cancer at the time they quit smoking. Studies were pooled with the random-effects model. RESULTS: Out of the 11,361 potential studies initially identified, we included 24 studies involving 969,560 individuals in our analysis. Lung cancer mortality varied across two groups: general quitters and peri-diagnosis quitters. For general quitters, those who had quit smoking for less than 10 years exhibited an RR of 0.64 (95% CI [0.55-0.76]), while those who quit for 10-20 years had an RR of 0.33 (0.25-0.43), over 20 years had an RR of 0.16 (0.11-0.24), and never-smokers had an RR at 0.11 (0.07-0.15). Among peri-diagnosis quitters, the 1-year Overall Survival (OS) showed an RR of 0.80 (0.67-0.96), the 2-year OS had an RR of 0.89 (0.80-0.98), the 3-year OS had an RR of 0.93 (0.84-1.03), and the 5-year OS had an RR of 0.85 (0.76-0.96). CONCLUSIONS: Earlier and longer smoking cessation is associated with reduced lung cancer mortality, no matter in which cessation stage for two different populations.

Response of microbial communities to exogenous nitrate nitrogen input in black and odorous sediment.

Since nitrate nitrogen (NO3--N) input has proved an effective approach for the treatment of black and odorous river waterbody, it was controversial whether the total nitrogen concentration standard should be raised when the effluent from the sewage treatment plant is discharged into the polluted river. To reveal the effect of exogenous nitrate (NO3--N) on black odorous waterbody, sediments with different features from contaminated rivers were collected, and the changes of physical and chemical characteristics and microbial community structure in sediments before and after the addition of exogenous NO3--N were investigated. The results showed that after the input of NO3--N, reducing substances such as acid volatile sulfide (AVS) in the sediment decreased by 80 % on average, ferrous (Fe2+) decreased by 50 %, yet the changing trend of ammonia nitrogen (NH4+-N) in some sediment samples increased while others decreased. High-throughput sequencing results showed that the abundance of Thiobacillus at most sites increased significantly, becoming the dominant genus in the sediment, and the abundance of functional genes in the metabolome increased, such as soxA, soxX, soxY, soxZ. Network analysis showed that sediment microorganisms evolved from a single sulfur oxidation ecological function to diverse ecological functions, such as nitrogen cycle nirB, nirD, nirK, nosZ, and aerobic decomposition. In summary, inputting an appropriate amount of exogenous NO3--N is beneficial for restoring and maintaining the oxidation states of river sediment ecosystems.

Country-specific net-zero strategies of the pulp and paper industry.

The pulp and paper industry is an important contributor to global greenhouse gas emissions1,2. Country-specific strategies are essential for the industry to achieve net-zero emissions by 2050, given its vast heterogeneities across countries3,4. Here we develop a comprehensive bottom-up assessment of net greenhouse gas emissions of the domestic paper-related sectors for 30 major countries from 1961 to 2019-about 3.2% of global anthropogenic greenhouse gas emissions from the same period5-and explore mitigation strategies through 2,160 scenarios covering key factors. Our results show substantial differences across countries in terms of historical emissions evolution trends and structure. All countries can achieve net-zero emissions for their pulp and paper industry by 2050, with a single measure for most developed countries and several measures for most developing countries. Except for energy-efficiency improvement and energy-system decarbonization, tropical developing countries with abundant forest resources should give priority to sustainable forest management, whereas other developing countries should pay more attention to enhancing methane capture rate and reducing recycling. These insights are crucial for developing net-zero strategies tailored to each country and achieving net-zero emissions by 2050 for the pulp and paper industry.

Preclinical Short-term and Long-term Safety of Human Bone Marrow Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) have become a promising therapeutic method. More safety data are needed to support clinical studies in more diseases. The aim of this study was to investigate the short- and long-term safety of human bone marrow-derived MSCs (hBMMSCs) in mice. In the present study, we injected control (saline infusion only), low (1.0 × 106/kg), medium (1.0 × 107/kg), and high (1.0 × 108/kg) concentrations of hBMMSCs into BALB/c mice. The safety of the treatment was evaluated by observing changes in the general condition, hematology, biochemical indices, pathology of vital organs, lymphocyte subsets, and immune factor levels on days 14 and 150. In the short-term toxicity test, no significant abnormalities were observed in the hematological and biochemical parameters between the groups injected with hBMMSCs, and no significant damage was observed in the major organs, such as the liver and lung. In addition, no significant differences were observed in the toxicity-related parameters among the groups in the long-term toxicity test. Our study also demonstrates that mice infused with different doses of hBMMSCs do not show abnormal immune responses in either short-term or long-term experiments. We confirmed that hBMMSCs are safe through a 150-day study, demonstrating that this is a safe and promising therapy and offering preliminary safety evidence to promote future clinical applications of hBMMSCs in different diseases.

Mesenchymal Stromal Cells Regulate M1/M2 Macrophage Polarization in Mice with Immune Thrombocytopenia.

Mesenchymal stromal cells have shown promising effects in the treatment of immune thrombocytopenia. However, the underlying mechanisms are not fully understood. In this study, we investigated the therapeutic effects of human bone marrow mesenchymal stromal cells (hBMSCs) and analyzed their unique role in regulating the M1/M2 macrophage ratio. We established a passive immune thrombocytopenia (ITP) mouse model and showed that there was a significant M1/M2 imbalance in ITP model mice by assessing the M1/M2 ratios in the liver, spleen, and bone marrow; we observed excessive activation of M1 cells and decreased M2 cell numbers in vivo. We have shown that systemic infusion of hBMSCs effectively elevated platelet levels after disease onset. Further analysis revealed that hBMSCs treatment significantly suppressed the number of proinflammatory M1 macrophages and enhanced the number of anti-inflammatory M2 macrophages; in addition, the levels of proinflammatory factors, such as interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), were significantly decreased in vivo, while the levels of the anti-inflammatory factor interleukin-10 (IL-10) were increased. In conclusion, our data suggest that hBMSCs treatment can effectively increase platelet counts, and the mechanism is related to the induction of macrophage polarization toward the anti-inflammatory M2 phenotype and the decrease in proinflammatory cytokine production, which together ameliorate innate immune disorders.

Development of a finite element full spine model with active muscles for quantitatively analyzing sarcopenia effects on lumbar load.

BACKGROUND AND OBJECTIVE: The musculoskeletal imbalance caused by disease is one of the most critical factors leading to spinal injuries, like sarcopenia. However, the effects of musculoskeletal imbalances on the spine are difficult to quantitatively investigate. Thus, a complete finite element spinal model was established to analyze the effects of musculoskeletal imbalance, especially concerning sarcopenia. METHODS: A finite element spinal model with active muscles surrounding the vertebrae was established and validated from anatomic verification to the whole spine model in dynamic loading at multiple levels. It was then coupled with the previously developed neuromuscular model to quantitatively analyze the effects of erector spinae (ES) and multifidus (MF) sarcopenia on spinal tissues. The severity of the sarcopenia was classified into three levels by changing the physiological cross-sectional area (PCSA) of ES and MF, which were mild (60% PCSA of ES and MF), moderate (48% PCSA of ES and MF), and severe (36% PCSA of ES and MF). RESULTS: The stress and strain levels of most lumbar tissues in the sarcopenia models were more significant than those of the normal model during spinal extension movement. The sarcopenia caused load concentration in several specific regions. The stress level of the L4-L5 intervertebral disc and L1 vertebra significantly increased with the severity of sarcopenia and showed relatively larger values than other segments. From the normal model to a severe sarcopenia model, the stress value of the L4-L5 intervertebral disc and L1 vertebra increased by 128% and 113%, respectively. The strain level of L5-S1 also inclined significantly with the severity of sarcopenia, and the relatively larger capsule strain values occurred at lower back segments from L3 to S1. CONCLUSIONS: In summary, the validated spinal coupling model can be used for spinal injury risk analysis caused by musculoskeletal imbalance. The results suggested that sarcopenia can primarily lead to high injury risk of the L4-L5 intervertebral disc, L1 vertebrae, and L3-S1 joint capsule regarding significant stress or strain variance.

Fatty infiltration of the cervical multifidus musculature and its clinical correlation to cervical spondylosis.

PURPOSE: Fat infiltration (FI) of the deep neck extensor muscles has been shown to be associated with poor outcomes in cervical injury, mechanical neck pain, and axial symptoms after cervical spine surgery. However, information is scarce on the severity of FI in cervical extensors associated with different clinical syndromes in patients with cervical spondylosis. OBJECTIVE: To investigate the relationship between the severity of FI in the cervical multifidus musculature and its clinical correlates in the syndromes and sagittal alignment of patients with cervical spondylosis. METHODS: This study was conducted as a retrospective study of twenty-eight healthy volunteers (HV) together with sixty-six patients who underwent cervical radiculopathy (CR), degenerative myelopathy (DM), and axial joint pain (AJP) from January 2020 to March 2022. MRI was used to measure the fat cross-sectional area (FCSA), functional muscle cross-sectional area (FMCSA), total muscle cross-sectional area (TMCSA), FI ratio of the cervical multifidus musculature at each cervical level from the C3 to C6 segments and the cervical lordosis angle in the included subjects. RESULTS: The difference in the FCSA and FI ratio in patient groups with cervical spondylosis was significantly greater than that of the HV group (P < 0.05), and the Cobb angle of the DM group, AJP group and HV group was significantly greater than that of the CR group (P < 0.05). The FI ratio comparison showed no significant difference by sex, and the comparison of FCSA, FMCSA, TMCSA and FI ratio showed no significant difference by age range from 35 to 69 in the included subjects. The FCSA and TMCSA in patients with cervical spondylosis were positively related to the Cobb angle (rs= 0.336, P = 0.006, rs =0.319, P = 0.009, respectively), and the FI ratio was inversely correlated with the Cobb angle (rs= -0.285, P = 0.020) and positively correlated with age (rs =0.261, P = 0.034). In the HV group, FMCSA was inversely correlated with age (rs= -0.400, P = 0.035), while the FI ratio had a positive correlation with age (rs= -0.423, P = 0.025). CONCLUSION: Compared with healthy subjects, a more severe degree of FI in the multifidus musculature and sagittal imbalance were found in patients with cervical spondylosis. These two imaging features are considered to be important concomitant phenomena of cervical spondylosis, and the more severe FI is, the worse the sagittal imbalance. However, each syndrome had no obvious difference in FI in the multifidus musculature.

Endoscopic Revision for Long-Term Symptomatic Cage Retropulsion after TLIF: The Clinical Presentation in a Single Center.

BACKGROUND: Cage retropulsion after transforaminal lumbar interbody fusion (TLIF) is a common complication that is more frequently detected in the early postoperative period. Revision in the early stages is relatively less difficult in symptomatic cases. However, cage retropulsion is quite rare for patients with intervertebral osseous fusion in the long term after TLIF, and there are no relevant reports related to the revision plan. CASE PRESENTATION: Here, we report a case of a patient who underwent L4-S1 TLIF at another hospital 4 years ago, accompanied by recurrent pain and discomfort of the left lower limb after the operation. Due to recent condition aggravation, it was considered to be caused by compression of the nerve root due to cage retropulsion. Nerve root sealing and endoscopy surgery were performed on the operative segment. It was found that cage retropulsion at the L4/5 level was a suspicious focus according to careful analysis of the clinical manifestations of the patient. Selective block of the nerve root on the level resulted in relief of the patient's original symptoms. After the posterior edge of the cage was exposed under the endoscope through an intervertebral foramen approach, the posterior edge of the cage protruding into the spinal canal was removed by high-speed burr grinding, working casing reduction and other methods. Postoperative symptoms of pain in the low back and lower limb were relieved completely. CONCLUSIONS: It is feasible to use the power system to remove the retrograde cage under the endoscope through the intervertebral foramen approach for the revision of symptomatic polyether ether ketone (PEEK) cage retropulsion in the long term after TLIF.

Vaccine-associated thrombocytopenia.

Vaccination is the most cost-effective means of preventing and even eliminating infectious diseases. However, adverse reactions after vaccination are inevitable. In addition to common vaccine-related adverse reactions, some rare but serious adverse reactions have been reported, including secondary immune thrombocytopenia (ITP). The measles-mumps-rubella (MMR) vaccine is currently the only vaccine for which a cause-effect relationship with immune thrombocytopenia has been demonstrated with an incidence of approximately 0.087-4 per 100,000 doses, and the complication is mostly observed in children. In addition, thrombocytopenia can be induced by coronavirus disease 2019 (COVID-19) vaccines following COVID-19 vaccination primarily occurs within a few weeks post-vaccination. The condition mostly occurs in elderly individuals with no sex differences. Its incidence is approximately 0.80 to 11.3 per million doses. Some patients have previously suffered from chronic ITP likely to develop exacerbation of ITP after COVID-19 vaccines, especially those who have undergone splenectomy or are being treated with >5 medications. Based on clinical practice, first-line treatments for vaccine-associated thrombocytopenia are essentially limited to those used for primary ITP, including glucocorticoids and intravenous immunoglobulin (IVIg).

Advancements of Prussian blue-based nanoplatforms in biomedical fields: Progress and perspectives.

Prussian blue (PB) nanoparticles possess excellent physicochemical properties, including imaging features, robust photothermal conversion ability, catalytic activity, surface modifiability, effective drug loading, good stability, biocompatibility and biodegradability. With the advancement of nanotechnology, diverse PB-based nanoplatforms have been developed for biomedical applications. This review systematically summarized recent studies on PB-based nanoplatforms in the treatment of tumor (photothermal therapy, photodynamic therapy, chemotherapy, immunotherapy, theranostics, etc.), cardiovascular and cerebrovascular diseases (restenosis, atherosclerosis, thrombosis, ischemic stroke, etc.), bacterial infections (photothermal sterilization, biofilms disruption, etc.), and other inflammation-related diseases (liver injury, acute pancreatitis, inflammatory bowel disease, osteoarthritis, etc.). Finally, the existing challenges associated with current studies are discussed, and the future possible research and application directions for PB-based nanoplatforms are proposed, providing paradigms for subsequent development.

Finite Element Analysis of Elbow Joint Stability by Different Flexion Angles of the Annular Ligament.

OBJECTIVE: The injury of the annular ligament can change the stress distribution and affect the stability of the elbow joint, but its biomechanical mechanism is unclear. The present study investigated the biomechanical effects of different flexion angles of the annular ligament on elbow joint stability. METHODS: A cartilage and ligament model was constructed using SolidWorks software according to the magnetic resonance imaging results to simulate the annular ligament during normal, loosened, and ruptured conditions at different buckling angles (0°, 30°, 60°, 90°, and 120°). The fixed muscle strengths were 40 N (F1), 20 N (F2), 20 N (F3), 20 N (F4), and 20 N (F5) for the triceps, biceps, and brachial tendons and the base of the medial collateral ligament and lateral collateral ligament. The different elbow three-dimensional (3D) finite element models were imported into ABAQUS software to calculate and analyze the load, contact area, contact stress, and stress of the medial collateral ligament of the olecranon cartilage. RESULTS: The results showed that the stress value of olecranon cartilage increased under different conditions (normal, loosened, and ruptured annular ligament) with elbow extension, and the maximum stress value of olecranon cartilage was 2.91 ± 0.24 MPa when the annular ligament was ruptured. The maximum contact area of olecranon cartilage was 254 mm2 with normal annular ligament when the elbow joint was flexed to 30°, while the maximum contact area of loosened and ruptured annular ligament was 283 and 312 mm2 at 60° of elbow flexion, and then decreased gradually. The maximum stress of the medial collateral ligament was 6.52 ± 0.23, 11.51 ± 0.78, and 18.74 ± 0.94 MPa under the different conditions, respectively. CONCLUSION: When the annular ligament ruptures, it should be reconstructed as much as possible to avoid the elevation of stress on the surface of the medial collateral ligament of the elbow and the annular cartilage, which may cause clinical symptoms.

Effect of the In Situ Screw Implantation Region and Angle on the Stability of Lateral Lumbar Interbody Fusion: A Finite Element Study.

OBJECTIVE: To investigate the effect of the in situ screw implantation region and angle on the stability of lateral lumbar interbody fusion (LLIF) from a biomechanical perspective. METHODS: A validated L2-4 finite element (FE) model was modified for simulation. The L3-4 fused segment undergoing LLIF surgery was modeled. The area between the superior and inferior edges and the anterior and posterior edges of the vertebral body (VB) is divided into four zones by three parallel lines in coronal and horizontal planes. In situ screw implantation methods with different angles based on the three parallel lines in coronal plane were applied in Models A, B, and C (A: parallel to inferior line; B: from inferior line to midline; C: from inferior line to superior line). In addition, four implantation methods with different regions based on the three parallel lines in horizontal plane were simulated as types 1-2, 1-3, 2-2, and 2-3 (1-2: from anterior line to midline; 1-3: from anterior line to posterior line; 2-2: parallel to midline; 2-3: from midline to posterior line). L3-4 ROM, interbody cage stress, screw-bone interface stress, and L4 superior endplate stress were tracked and calculated for comparisons among these models. RESULTS: The L3-4 ROM of Models A, B, and C decreased with the extent ranging from 47.9% (flexion-extension) to 62.4% (lateral bending) with no significant differences under any loading condition. Types 2-2 and 2-3 had 45% restriction, while types 1-2 and 1-3 had 51% restriction in ROM under flexion-extension conditions. Under lateral bending, types 2-2 and 2-3 had 70.6% restriction, while types 1-2 and 1-3 had 61.2% restriction in ROM. Under axial rotation, types 2-2 and 2-3 had 65.2% restriction, while types 1-2 and 1-3 had 59.3% restriction in ROM. The stress of the cage in types 2-2 and 2-3 was approximately 20% lower than that in types 1-2 and 1-3 under all loading conditions in all models. The peak stresses at the screw-bone interface in types 2-2 and 2-3 were much lower (approximately 35%) than those in types 1-2 and 1-3 under lateral bending, while no significant differences were observed under flexion-extension and axial rotation. The peak stress on the L4 superior endplate was approximately 30 MPa and was not significantly different in all models under any loading condition. CONCLUSIONS: Different regions of entry-exit screws induced multiple screw trajectories and influenced the stability and mechanical responses. However, different implantation angles did not. Considering the difficulty of implantation, the ipsilateral-contralateral trajectory in the lateral middle region of the VB can be optimal for in situ screw implantation in LLIF surgery.

Macrophage mitochondrial fission improves cancer cell phagocytosis induced by therapeutic antibodies and is impaired by glutamine competition.

Phagocytosis is required for the optimal efficacy of many approved and promising therapeutic antibodies for various malignancies. However, the factors that determine the response to therapies that rely on phagocytosis remain largely elusive. Here, we demonstrate that mitochondrial fission in macrophages induced by multiple antibodies is essential for phagocytosis of live tumor cells. Tumor cells resistant to phagocytosis inhibit mitochondrial fission of macrophages by overexpressing glutamine-fructose-6-phosphate transaminase 2 (GFPT2), which can be targeted to improve antibody efficacy. Mechanistically, increased cytosolic calcium by mitochondrial fission abrogates the phase transition of the Wiskott-Aldrich syndrome protein (WASP)-Wiskott-Aldrich syndrome interacting protein (WIP) complex and enables protein kinase C-θ (PKC-θ) to phosphorylate WIP during phagocytosis. GFPT2-mediated excessive use of glutamine by tumor cells impairs mitochondrial fission and prevents access of PKC-θ to compartmentalized WIP in macrophages. Our data suggest that mitochondrial dynamics dictate the phase transition of the phagocytic machinery and identify GFPT2 as a potential target to improve antibody therapy.

Quantitative cervical spine injury responses in whiplash loading with a numerical method of natural neural reflex consideration.

BACKGROUND AND OBJECTIVE: Neural reflex is hypothesized as a regulating step in spine stabilizing system. However, neural reflex control is still in its infancy to consider in the previous finite element analysis of head-neck system for various applications. The purpose of this study is to investigate the influences of neural reflex control on neck biomechanical responses, then provide a new way to achieve an accurate biomechanical analysis for head-neck system with a finite element model. METHODS: A new FE head-neck model with detailed active muscles and spinal cord modeling was established and globally validated at multi-levels. Then, it was coupled with our previously developed neuromuscular head-neck model to analyze the effects of vestibular and proprioceptive reflexes on biomechanical responses of head-neck system in a typical spinal injury loading condition (whiplash). The obtained effects were further analyzed by comparing a review of epidemiologic data on cervical spine injury situations. RESULT: The results showed that the active model (AM) with neural reflex control obviously presented both rational head-neck kinematics and tissue injury risk referring to the previous experimental and epidemiologic studies, when compared with the passive model (PM) without it. Tissue load concentration locations as well as stress/strain levels were both changed due to the muscle activation forces caused by neural reflex control during the whole loading process. For the bony structures, the AM showed a peak stress level accounting for only about 25% of the PM. For the discs, the stress concentrated location was transferred from C2-C6 in the PM to C4-C6 in the AM. For the spinal cord, the strain concentrated locations were transferred from C1 segment to around C4 segment when the effects of neural reflex control were implemented, while the gray matter and white matter peak strains were reduced to 1/3 and 1/2 of the PM, respectively. All these were well correlated with epidemiological studies on clinical cervical spine injuries. CONCLUSION: In summary, the present work demonstrated necessity of considering neural reflex in FE analysis of a head-neck system as well as our model biofidelity. Overall results also verified the previous hypothesis and further quantitatively indicated that the muscle activation caused by neural reflex is providing a protection for the neck in impact loading by decreasing the strain level and changing the possible injury to lower spinal cord level to reduce injury severity.

Percutaneous Endoscopic Lumbar Discectomy for Lumbar Disc Herniation Using an Endoscopic Staining: A Technical Note.

Symptomatic lumbar disc herniation (LDH) is widely treated using percutaneous endoscopic lumbar discectomy (PELD). In the present PELD surgery, performing decompression under endoscope still takes a long time to explore the rupture site of annulus fibrosus, resulting in prolonged operation time and over-invasion of the undegenerated annulus fibrosus. A wide range of intraoperative exploration also induces an iatrogenic injury of the normal annulus fibrosus, even aggravating intervertebral disc degeneration, which may lead to early postoperative recurrence in severe case. Hence, it is important to seek a precise decompression in PELD surgery. Under this kind of realization, more spinal surgeons possibly choose a disc staining before performing decompression. However, the classical disc staining technique still has its shortcomings. First of all, an appropriate dose of staining cannot be accurately mastered, even induces unqualified staining effect. Second, the duration of surgery and the times of fluoroscopy will be increased. Finally, what surgeons see under the endoscope is the staining result but not the staining process. Hence, this is accomplished more effectively by designing procedures that perform fully visible disc staining under spinal endoscope. There is no specific research to discuss the technique note of endoscopic staining in PELD surgery. We have come up with a new original technology of endoscopic staining with methylene blue injection in PELD for treatment of LDH.

Finite Element Analysis of Insertion Angle of Absorbable Screws for the Fixation of Radial Head Fractures.

OBJECTIVE: To investigate the biomechanical effects of different insertion angles of absorbable screws for the fixation of radial head fractures. METHODS: The finite element models used to simulate the fractures were created based on CT scans. Two absorbable screws were used to fix and maintain the stability of the fracture, and the angles between the screws were set to 0°, 15°, 30°, 45°, 60°, 75°, and 90°. A downward force of 100 N was applied at the stress point, which was coupled with the surface, and the distal radius was limited to six degrees of freedom. The direction and location of the applied force were the same in each model. The values of the von Mises stress and peak displacements were calculated. RESULTS: Under the applied load and different screw angles, the maximum von Mises stress in the screws was concentrated on the surface contacting the fracture surfaces. The maximum von Mises equivalent stress in the screw decreased when the angle increased from 0° (19.54 MPa) to 45° (13.11 MPa) and increased when the angle further increased to 90° (24.63 MPa). The peak displacement decreased as the angle increased from 0° (0.19 mm) to 45° (0.15 mm) and increased when the angle further increased to 90° (0.25 mm). CONCLUSION: The computational stress distribution showed that fixation with absorbable screws is safe for patients. Moreover, the minimum von Mises stress and displacements were generated when the angle between the screws was 45°; hence, this setting should be recommended for Mason type II radial fractures.