Digital anatomical study and clinical application of the ideal S2 alar-lliac screw trajectory.

BACKGROUND: To investigate the ideal trajectory for the S2AI screw and to clinically validate its safety feasibility. METHODS: The 3D model was reconstructed from CT data of the pelvis of 30 selected adults, and the 3D coordinate system was established with the first sacral superior endplate as the horizontal plane. A set of cutting planes was made at 3 mm intervals in the coronal plane, and the cross-sectional internal tangent circles were divided in the target area. Using the linear fitting function, the axis of 90 mm length was calculated by the least squares method for each inner tangent circle center. The diameter of the axis is gradually increased until the first contact with the cortex, and the cylindrical model is the ideal screw trajectory. The intersection of the axis and the dorsal cortex is the screw placement point, which is located by Horizon Distance (HD) and Vertical Distance (VD); the diameter of the screw trajectory (d) is the diameter of the cylindrical model; the direction of the screw trajectory is determined by Sagittal Angle (SA) and Transverse Angle (TA). The screw trajectory orientation is determined by Sagittal Angle (SA) and Transverse Angle (TA). Based on the ideal screw trajectory, the 3D printed surgical guide and freehand techniques were used to verify its safety feasibility, respectively. RESULTS: The screw placement points [HD (4.7 ± 1.0) mm, VD (19.7 ± 1.9) mm], screw placement directions [SA (31.3°±2.3°), TA (42.4°±2.3°)], and screw dimensions for the ideal screw trajectory of the S2AI were combined for analysis. (L is 90 mm, d is 13.2 ± 1.4 mm). The S2AI screw superiority rate [96.6% (56/58)] and reasonable rate [100%] were higher in the guide group than in the freehand group [90.0% (63/70), 97.1% (68/70)], but the differences were not statistically significant (P > 0.05). Although screws invaded the cortex in both groups, there were no associated adverse events in either group. CONCLUSION: The S2AI screw-based ideal trajectory placement is a safe, feasible and accurate method of screw placement.

A prospective cohort study: platelet-rich plasma combined with carpal tunnel release treating carpal tunnel syndrome.

BACKGROUND: PRP injection was proved to promote the health condition of individuals with mild to moderate Carpal Tunnel Syndrome (CTS). However, carpal tunnel release (CTR) was still a necessary treatment for individuals with moderate and severe CTS. METHODS: To explore whether adjuvant PRP treatment would improve the prognosis while using CTR, we included 82 patients in this study. Preoperative and postoperative visual analog scale (VAS), Boston carpal tunnel syndrome questionnaire-symptom severity scale (BCTQ-SSS), Boston carpal tunnel syndrome questionnaire-functional status scale (BCTQ-FSS), and grip strength were used to examine the patient's symptoms and function. RESULTS: CTR combined with PRP treatment improved the VAS (1.9 ± 0.5 versus 1.4 ± 0.4, P < .05), BCTQ-SSS (1.8 ± 0.4versus 1.5 ± 0.3, P < .05) and BCTQ-FSS (1.8 ± 0.5 versus 1.4 ± 0.6, P < .05) in patients with moderate symptoms within one month after surgery. At the same time, it does not show any advantages in treating individuals with severe carpal tunnel syndrome. CONCLUSIONS: PRP does not affect long-term prognosis while increasing the surgery cost. To conclude, PRP as an adjuvant treatment of CTR has limited effect. Considering the additional financial burden on patients, CTR combined with PRP should be cautious in CTS treatment.

K2S2O8-mediated regio- and stereo-selective thiocyanation of enamides with NH4SCN.

A direct and straightforward thiocyanation of enamides with NH4SCN under metal-free conditions has been accomplished. A variety of (E)-ß-thiocyanoenamides are readily produced in a regio- and stereo-selective manner. The protocol features mild reaction conditions, good functional group tolerance and operational simplicity. The potential utility of this strategy was further demonstrated by transformation of thiocyanate into thiotetrazole-containing compounds and a Pd-catalyzed cross-coupling reaction to afford six- or seven-membered sulfur-containing heterocycles. Mechanistic insights into the reaction indicate that the reaction may proceed via a radical mechanism.

UV-Vis-NIR Full-Range Responsive Carbon Dots with Large Multiphoton Absorption Cross Sections and Deep-Red Fluorescence at Nucleoli and In Vivo.

Carbon dots (CDs), with excellent optical property and cytocompatibility, are an ideal class of nanomaterials applied in the field of biomedicine. However, the weak response of CDs in the near-infrared (NIR) region impedes their practical applications. Here, UV-vis-NIR full-range responsive fluorine and nitrogen doped CDs (N-CDs-F) are designed and synthesized that own a favorable donor-π-acceptor (D-π-A) configuration and exhibit excellent two-photon (λex = 1060 nm), three-photon (λex = 1600 nm), and four-photon (λex = 2000 nm) excitation upconversion fluorescence. D-π-A-conjugated CDs prepared by solvothermal synthesis under the assistance of ammonia fluoride are reported and are endowed with larger multiphoton absorption (MPA) cross sections (3PA: 9.55 × 10-80 cm6 s2 photon-2 , 4PA: 6.32 × 10-80 cm8 s3 photon-3 ) than conventional organic compounds. Furthermore, the N-CDs-F show bright deep-red to NIR fluorescence both in vitro and in vivo, and can even stain the nucleoli of tumor cells. A plausible mechanism is proposed on the basis of the strong inter-dot and intra-dot hydrogen bonds through NH···F that can facilitate the expanding of conjugated sp2 domains, and thus not only result in lower highest occupied molecular orbital-lowest unoccupied molecular orbital energy level but also larger MPA cross sections than those of undoped CDs.

A 3D-printed, personalized, biomechanics-specific beta-tricalcium phosphate bioceramic rod system: personalized treatment strategy for patients with femoral shaft non-union based on finite element analysis.

BACKGROUND: Although double-plate fixation (DP), i.e., fixation with a combination of a main lateral plate (LP) and a support medial plate (MP), is a relatively mature method for treating femoral shaft non-union with bone defect causes complications. The purpose of this study was to evaluate LP fixation with a 3D-printed, personalized, biomechanics-specific ß-TCP bioceramic rod system (LP + 3DpbsBRS) as an alternative with less collateral damage. METHODS: Structure-specific finite element modelling was used to simulate femoral shaft non-union with bone defects and treatment with an LP only as the blank control. Then, the peak von Mises stress (VMS), the VMS distribution, and the plate displacement were determined to compare the effectiveness of LP + CBG (cancellous bone grafting), DP + CBG, and LP + 3DpbsBRS under 850 N of axial force. RESULTS: Our results indicated that the peak VMS was 260.2 MPa (LP + 3DpbsBRS), 249.6 MPa (MP in DP + CBG), 249.3 MPa (LP in DP + CBG), and 502.4 MPa (LP + CBG). The bending angle of the plate was 1.2° versus 1.0° versus 1.1° versus 2.3° (LP + 3DpbsBRS versus MP in DP + CBG versus LP in DP + CBG versus LP + CBG). CONCLUSION: The 3DpbsBRS in the LP + 3DpbsBRS group could replace the MP in the DP + CBG group by providing similar medial mechanical support. Furthermore, avoiding the use of an MP provides better protection of the soft tissue and vasculature.

Overexpressed N-fucosylation on the cell surface driven by FUT3, 5, and 6 promotes cell motilities in metastatic pancreatic cancer cell lines.

Pancreatic cancer is a highly malignant tumor of the digestive system. Previous studies have shown that abnormal cell surface glycosylation is associated with cancer metastasis, which suggests that glycosylation changes may open a new window for discovering metastasis-related pathways. In this study, we used a microarray with 55 lectins to screen for altered glycosylation between two metastatic pancreatic cancer lines (Capan-1 and Su.86.86) and two nonmetastatic pancreatic cancer lines (Panc-1 and MIA PaCa-2), and we further analyzed three lectins with high-binding activities (AAL, UEA-I, and PHA-E) in cell motility assays using these pancreatic cancer cells to detect whether blocking certain forms of cell surface glycosylation affects any processes associated with metastasis. As a result, we found that AAL, a fucose-specific lectin, has different binding patterns between metastatic pancreatic cancer and nonmetastatic pancreatic cancer lines and inhibits cell motility in metastatic pancreatic cancer cells. Furthermore, the N-fucosylation-related genes FUT3, 5, and 6 were found to be responsible for the elevated fucosylation in metastatic pancreatic cells through real-time PCR screening. In summary, our findings that the specific bindings of AAL on cell surfaces and highly expressed FUT3, 5, and 6 in metastatic pancreatic cancer cells, although preliminary, are encouraging, and our established combined method is also suitable for discovering metastasis-related mechanisms in other cancers.

Glucocorticoid-activated IRE1α/XBP-1s signaling: an autophagy-associated protective pathway against endotheliocyte damage.

Glucocorticoid-induced endothelial injury has been reported in several diseases. Although there are several theories, the exact mechanism underlying the role of glucocorticoids in this process remains unclear. Autophagy has been reported to occur as a response to different stimuli and can affect cell survival and function. In this study, we found that glucocorticoids induced apoptosis and endoplasmic reticulum (ER) stress in endotheliocytes. Furthermore, we discovered that glucocorticoids induced autophagy in these cells and the inositol requiring protein 1 (IRE1α)/X-box binding protein 1s (XBP-1s) axis, one of the downstream signaling pathways of ER stress, was associated with the glucocorticoid-induced autophagy. The autophagy partly protected endotheliocytes from glucocorticoid-induced apoptosis and inhibition of proliferation. In conclusion, glucocorticoid-induced endoplasmic reticulum stress activated the IRE1α/XBP-1s signaling and induced autophagy, which, in turn, played a protective role in endotheliocyte survival and proliferation, avoiding further cellular damage caused by glucocorticoids.

Advances in the research on myokine-driven regulation of bone metabolism.

The traditional view posits that bones and muscles interact primarily through mechanical coupling. However, recent studies have revealed that myokines, proteins secreted by skeletal muscle cells, play a crucial role in the regulation of bone metabolism. Myokines are widely involved in bone metabolism, influencing bone resorption and formation by interacting with factors related to bone cell secretion or influencing bone metabolic pathways. Here, we review the research progress on the myokine regulation of bone metabolism, discuss the mechanism of myokine regulation of bone metabolism, explore the pathophysiological relationship between sarcopenia and osteoporosis, and provide future perspectives on myokine research, with the aim of identify potential specific diagnostic markers and therapeutic entry points.

Economical one-pot synthesis of isoquercetin and D-allulose from quercetin and sucrose using whole-cell biocatalyst.

Isoquercetin and D-allulose have diverse applications and significant value in antioxidant, antibacterial, antiviral, and lipid metabolism. Isoquercetin can be synthesized from quercetin, while D-allulose is converted from D-fructose. However, their production scale and overall quality are relatively low, leading to high production costs. In this study, we have devised a cost-effective one-pot method for biosynthesizing isoquercetin and D-allulose using a whole-cell biocatalyst derived from quercetin and sucrose. To achieve this, the optimized isoquercetin synthase and D-allulose-3-epimerase were initially identified through isofunctional gene screening. In order to reduce the cost of uridine diphosphate glucose (UDPG) during isoquercetin synthesis and ensure a continuous supply of UDPG, sucrose synthase is introduced to enable the self-circulation of UDPG. At the same time, the inclusion of sucrose permease was utilized to successfully facilitate the catalytic production of D-allulose in whole cells. Finally, the recombinant strain BL21/UGT-SUS+DAE-SUP, which overexpresses MiF3GTMUT, GmSUS, EcSUP, and DAEase, was obtained. This strain co-produced 41±2.4 mg/L of isoquercetin and 5.7±0.8 g/L of D-allulose using 120 mg/L of quercetin and 20 g/L of sucrose as substrates for 5 h after optimization. This is the first green synthesis method that can simultaneously produce flavonoid compounds and rare sugars. These findings provide valuable insights and potential for future industrial production, as well as practical applications in factories.

Transparent multifunctional cellulose-based conductive hydrogel for wearable strain sensors and arrays.

Conductive hydrogels as promising candidate materials for flexible strain sensors have gained considerable attentions. However, it is still a great challenge to construct hydrogel with multifunctional performance via natural polymer. Herein, a novel multifunctional conductive hydrogel based on methylcellulose and cellulose nanocrystal was prepared via a facile and low-cost strategy. Methylcellulose (MC) was introduced to not only guarantee the stability of tannic acid coated cellulose nanocrystal (TA@CNCs) in LiCl solution, but also improve anti-freezing ability. The obtained hydrogel exhibited high transparency (98 % at 800 nm), good stretchability (663.1 %), low temperature tolerance (-23.9 °C), superior conductivity (2.89 S/m) and excellent UV shielding behavior. Flexible strain sensor assembled by the prepared hydrogels can be used to detect human body motions include subtle and large motions, and exhibited good sensitivity and stability over a wide temperature range. Multiple flexible hydrogels can also be assembled into a 3D sensor array to detect the distribution and magnitude of spatial pressure. Therefore, the hydrogels prepared via natural polymers will have broad application prospects in wearable devices, electronic skin and multifunctional sensor components.

Three-dimensional spine reconstruction from biplane radiographs using convolutional neural networks.

PURPOSE: The purpose of this study was to develop and evaluate a deep learning network for three-dimensional reconstruction of the spine from biplanar radiographs. METHODS: The proposed approach focused on extracting similar features and multiscale features of bone tissue in biplanar radiographs. Bone tissue features were reconstructed for feature representation across dimensions to generate three-dimensional volumes. The number of feature mappings was gradually reduced in the reconstruction to transform the high-dimensional features into the three-dimensional image domain. We produced and made eight public datasets to train and test the proposed network. Two evaluation metrics were proposed and combined with four classical evaluation metrics to measure the performance of the method. RESULTS: In comparative experiments, the reconstruction results of this method achieved a Hausdorff distance of 1.85 mm, a surface overlap of 0.2 mm, a volume overlap of 0.9664, and an offset distance of only 0.21 mm from the vertebral body centroid. The results of this study indicate that the proposed method is reliable.

Chitosan-based transparent and conductive hydrogel with highly stretchable, adhesive and self-healing as skin-like sensor.

Hydrogel sensors attained increasing attention due to their excellent mechanical and sensing properties. However, it is still a big challenge to fabricate hydrogel sensors with multifunctional properties of transparent, high stretchability, self-adhesive and self-healing ability. In this study, chitosan as a natural polymer has been employed to construct a polyacrylamide-chitosan-Al3+ (PAM-CS-Al3+) double network (DN) hydrogel with high transparency (>90 % at 800 nm), good electrical conductivity (up to 5.01 S/m) and excellent mechanical properties (strain and toughness as high as 1040 % and 730 kJ/m3). Moreover, the dynamic ionic and hydrogen bond interaction between PAM and CS endowed the PAM-CS-Al3+ hydrogel good self-healing ability. In addition, the hydrogel possesses good self-adhesive ability on different substrates, including glass, wood, metal, plastic, paper, polytetrafluoroethylene (PTFE) and rubber. Most importantly, the prepared hydrogel could be assembled into transparent, flexible, self-adhesive, self-healing and high sensitive strain/pressure sensor for monitoring human body movement. This work may pave the way for fabricating the multifunctional chitosan-based hydrogels which has potential application in the fields of wearable sensor and soft electronic devices.

Highly stretchable, tough and conductive chitin nanofiber composite hydrogel as a wearable sensor.

To meet the requirements of eco-friendly and sustainability in the 21st century, hydrogels based on biopolymer with conductivity and stretchable property have attained increasing attention for strain sensor. However, the as-prepared of hydrogel sensor with excellent mechanical property and high strain sensitivity is still a challenge. In this study, chitin nanofiber (ChNF) reinforced composite hydrogels of PACF are fabricated via a facile one-pot method. The obtained PACF composite hydrogel exhibits good transparency (80.6 % at 800 nm)and excellent mechanical properties (tensile strength, 261.2 kPa; tensile strain as high as 550.3 %). Moreover, the composite hydrogels also demonstrate excellent anti-compression performance. The composite hydrogels own good conductivity (1.20 S/m) and strain sensitivity. Most importantly, the hydrogel can be assembled as a strain/pressure sensor for detecting large-scale and small-scale human motion. Therefore, flexible conductive hydrogel strain sensors will have broad application prospects in artificial intelligence, electronic skin, and personal health.

Surface modification of chitin nanofibers with dopamine as efficient nanosorbents for enhanced removal of dye pollution and metal ions.

The development of environmentally friendly and low-cost adsorbents with high adsorption capacity remains a challenge. Herein, chitin nanofiber-polydopamine composite materials (CNDA) have been obtained by surface modification of chitin nanofiber using dopamine. According to the results of transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier Transform Infrared Spectrometer (FTIR), and X-ray photoelectron spectrometer (XPS), polydopamine have been successfully coated on the surface of chitin nanofiber (ChNF). The ability to remove methylene blue (MB) has been analyzed via standard adsorption experiments, indicating that the maximum adsorption capacity (qmax) can reach 196.6 mg/g at MB initial concentration of 50 mg/L. Most importantly, the adsorption kinetics, isotherm, and thermodynamics were used to investigate the MB adsorption mechanism on composites. This indicated that the polydopamine on the surface of chitin nanofiber (ChNF) plays an important role in the MB dye adsorption. Moreover, the removal ability of CNDA to metal ions has also been investigated, indicating high capacities for Fe3+, Mn2+, Cu2+, and Ni2+. Based on their biodegradability and good adsorption capacity, the CNDA composite material can be considered a promising adsorbent for wastewater treatment.

[Effects of umbilical moxibustion on phobic behavior and monoamine neurotransmitters in stress-model rats].

OBJECTIVE: To investigate the effects of umbilical moxibustion therapy on phobic behavior and the contents of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in different brain regions of the stress-model rats and explore the potential mechanism of umbilical moxibustion on phobic behavior. METHODS: Among 50 Wistar male rats, 45 rates were selected and randomly divided into a control group, a model group and an umbilical moxibustion group, 15 rats in each one; and the rest 5 rats were used for preparing the model of electric shock. The bystander electroshock method was adopted to prepare phobic stress model in the model group and the umbilical moxibustion group. After modeling, the intervention with umbilical moxibustion started in the umbilical moxibustion group, in which, the ginger-isolated moxibustion was applied at "Shenque" (CV 8), once daily, 2 cones for 20 min each time, for consecutively 21 days. After modeling and intervention completed, the rats in each group were subjected to the open field test to evaluate the state of fear. After intervention, the Morris water maze test and fear conditioning test were performed to evaluate the changes in learning and memory ability and the state of fear. Using high performance liquid chromatography (HPLC), the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were determined. RESULTS: Compared with the control group, the horizontal and vertical activity scores were lower (P<0.01), the number of stool particles was increased (P<0.01), the escape latency was prolonged (P<0.01), the times of target quadrant were reduced (P<0.01), and the freezing time was prolonged (P<0.05) in the rats of the model group. The horizontal and vertical activity scores were increased (P<0.05), the number of stool particles was reduced (P<0.05), the escape latency was shortened (P<0.05, P<0.01), the times of target quadrant were increased (P<0.05), and the freezing time was shortened (P<0.05) in the rats of the umbilical moxibustion group when compared with the model group. The trend search strategy was adopted in the control group and the umbilical moxibustion group, while the random search strategy was used in rats of the model group. Compared with the control group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were reduced (P<0.01) in the model group. In the umbilical moxibustion group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were increased (P<0.05, P<0.01) when compared with the model group. CONCLUSION: Umbilical moxibustion can effectively relieve the state of fear and learning and memory impairment of phobic stress model rats, which may be related to the up-regulation of contents of brain neurotransmitters, i.e. NE, DA, and 5-HT.

Promotion of the genipin crosslinked chitosan-fiber hydrogel loaded with sustained release of clemastine fumarate in diabetic wound repair.

Diabetic skin disorders are lingering and refractory clinical diseases. In this study, a genipin-crosslinked porous chitosan fiber (CSF) hydrogel was fabricated to achieve rapid wound healing. By embedding clemastine fumarate (CF) in the CSF hydrogel pores, we synthesised a CSF/CF hydrogel for the treatment of diabetic wounds. The microstructure, chemical elements, spectral variation, mechanical properties, swelling ratios, degradability, and toxicity of the CSF/CF hydrogels were studied. Compared with the typical CS power hydrogel, the porous CSF hydrogel crosslinked with genipin possesses a stable structure and improved physicochemical properties. Moreover, CF was slowly released from the CSF hydrogel. Molecular simulation also showed that CF was evenly embedded inside the cavity formed by the novel CSF hydrogel. The results suggested that CF can resist damage from high glucose levels and promote proliferation, tube formation, and migration of endothelial cells (ECs) and fibroblasts. The CSF/CF hydrogel promoted wound healing in a rat model. Mechanistically, the beneficial effect of CF on wound healing may be related to activation of the MEK/ERK and PI3K/Akt signalling pathways. In conclusion, genipin-crosslinked CSF/CF hydrogel can accelerate wound healing and may be an effective therapeutic method for treating diabetic skin lesions.

Downregulation of FTO in the hippocampus is associated with mental disorders induced by fear stress during pregnancy.

Mental disorders (MD), such as anxiety, depression, and cognitive impairment, are very common during pregnancy and predispose to adverse pregnancy outcomes; however, the underlying mechanisms are still under intense investigation. Although the most common RNA modification in epigenetics, N6-methyladenosine (m6A) has been widely studied, its role in MD has not been investigated. Here, we observed that fat mass and obesity-associated protein (FTO) are downregulated in the hippocampus of pregnant rats with MD induced by fear stress and demonstrated that FTO participates in and regulates MD induced by fear stress. In addition, we identified four genes with anomalous modifications and expression (double aberrant genes) that were directly regulated by FTO, namely Angpt2, Fgf10, Rpl21, and Adcy7. Furthermore, we found that these genes might induce MD by regulating the PI3K/Akt and Rap1 signaling pathways. It appears that FTO-mediated m6A modification is a key regulatory mechanism in MD caused by fear stress during pregnancy.

Causal Genetic Loci for a Motivated Behavior Spectrum Harbor Psychiatric Risk Genes.

Behavioral diversity is critical for population fitness. Individual differences in risk-taking are observed across species, but underlying genetic mechanisms and conservation are largely unknown. We examined dark avoidance in larval zebrafish, a motivated behavior reflecting an approach-avoidance conflict. Brain-wide calcium imaging revealed significant neural activity differences between approach-inclined versus avoidance-inclined individuals. We used a population of ∼6,000 to perform the first genome-wide association study (GWAS) in zebrafish, which identified 34 genomic regions harboring many genes that are involved in synaptic transmission and human psychiatric diseases. We used CRISPR to study several causal genes: serotonin receptor-1b ( htr1b ), nitric oxide synthase-1 ( nos1 ), and stress-induced phosphoprotein-1 ( stip1 ). We further identified 52 conserved elements containing 66 GWAS significant variants. One encoded an exonic regulatory element that influenced tissue-specific nos1 expression. Together, these findings reveal new genetic loci and establish a powerful, scalable animal system to probe mechanisms underlying motivation, a critical dimension of psychiatric diseases.

Fear Stress During Pregnancy Affects Placental m6A-Modifying Enzyme Expression and Epigenetic Modification Levels.

As the hub connecting mother and offspring, the placenta's normal development is vital for fetal growth. Fear stress can cause some structural alterations in the placenta and affect placental development and function. N6-methyladenosine (m6A) is the most common mRNA modification and is involved in regulating the development of the placenta and embryo. There are no reports on the potential role of m6A modification in placental damage caused by fear stress during pregnancy. In this study, we demonstrated that fear stress during pregnancy increases the levels of methylated enzymes (METTL3, METTL14, and WTAP), decreases the levels of demethylase FTO, and increases the overall methylation levels in the placenta of pregnant rats. MeRIP-seq data analysis revealed 22,010 m6A peaks associated with 12,219 genes in the placenta of the model and 21,060 m6A peaks associated with 11,730 genes in the placenta of the control. The peaks were mainly concentrated in the coding region and the 3' untranslated region. In addition, 50 genes with abnormal modification and expression (double aberrant genes) were screened out by combining MeRIP-seq and RNA-seq data. Mefv, Erbb2, and Cgas were selected from 50 double aberrant genes, and MeRIP-qPCR and real-time quantitative polymerase chain reaction were used to verify their modification and expression levels. Our findings suggest that m6A modifications play an important role in placental dysfunction induced by fear stress during pregnancy.

Neuropilin-1-Mediated SARS-CoV-2 Infection in Bone Marrow-Derived Macrophages Inhibits Osteoclast Differentiation.

In humans, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause medical complications across various tissues and organs. Despite the advances to understanding the pathogenesis of SARS-CoV-2, its tissue tropism and interactions with host cells have not been fully understood. Existing clinical data have revealed disordered calcium and phosphorus metabolism in Coronavirus Disease 2019 (COVID-19) patients, suggesting possible infection or damage in the human skeleton system by SARS-CoV-2. Herein, SARS-CoV-2 infection in mouse models with wild-type and beta strain (B.1.351) viruses is investigated, and it is found that bone marrow-derived macrophages (BMMs) can be efficiently infected in vivo. Single-cell RNA sequencing (scRNA-Seq) analyses of infected BMMs identify distinct clusters of susceptible macrophages, including those related to osteoblast differentiation. Interestingly, SARS-CoV-2 entry on BMMs is dependent on the expression of neuropilin-1 (NRP1) rather than the widely recognized receptor angiotensin-converting enzyme 2 (ACE2). The loss of NRP1 expression during BMM-to-osteoclast differentiation or NRP1 neutralization and knockdown can significantly inhibit SARS-CoV-2 infection in BMMs. Importantly, it is found that authentic SARS-CoV-2 infection impedes BMM-to-osteoclast differentiation. Collectively, this study provides evidence for NRP1-mediated SARS-CoV-2 infection in BMMs and establishes a potential link between disturbed osteoclast differentiation and disordered skeleton metabolism in COVID-19 patients.