A Novel 5-Chloro-N-Phenyl-1 H-Indole-2-carboxamide Derivative as a Glycogen Phosphorylase Inhibitor: Evaluating the Long-Term Drug Effects on Muscle Function for the First Time.

Compound 1 was previously identified by our team as a glycogen phosphorylase (GP) inhibitor with glucose-lowering activity and demonstrated to have protective effects against myocardial and cerebral ischemia. However, its impact on muscle function has not been clarified. This study is the first to evaluate the long-term effects of GP inhibitors on muscle function and metabolism. After a 28-day administration of Compound 1, we performed assays to assess muscle function and biochemical parameters in rats. We observed reductions in peak holding force, duration, tetanic contraction force, single-contraction force, and electromyographic signals under 20 s and 10 min contraction stimuli. The metabolic analysis showed no significant effects on muscle glycogen, ATP, lactic acid, and uric acid levels at low doses. In contrast, medium to high doses resulted in increased glycogen, decreased ATP, and reduced lactic acid (only at high doses), without affecting uric acid. These findings suggest that Compound 1 may adversely affect muscle function in rats, potentially due to the glycogen inhibition effects of GP inhibitors. This study provides crucial safety data and insights into the long-term effects of GP inhibitors on rat muscles, which will guide future developments and applications.

Effects of saponins Rb1 and Re in American ginseng combined intervention on immune system of aging model.

Aging is a major risk factor for the development of many pathological processes, such as reduced immunity, cancer, cardiovascular diseases or neurodegenerative diseases, while age-related chronic diseases are the most common causes of death. This paper studies the effects of American ginseng saponin Rb1 and Re alone and combined intervention on the immune system of aging mouse models, by using 30 mg/kg Rb1, 15 mg/kg Re, and Rb1 + Re (30 mg/kg Rb1 and 15 mg/kg Re (co-intervention) was used to intervene in the aging model, and immune indicators such as thymus index, spleen index, interleukin and interferon were detected to evaluate the impact of Rb1 and Re on immune function. The results show that Rb1 and Re intervention alone can increase the spleen index by 7%-12% and the thymus index by 12%-19% in the aging model. After Rb1 or Re alone intervened, the apoptotic cells in the thymus were slightly reduced, and the proportion of apoptotic cells was reduced. The combination of Rb1 + Re can promote the thymus index and spleen index to increase by 23.40% and 25.5% respectively, which is more advantageous than Rb1 or Re alone. In addition, Rb1 and Re intervention can reduce the level of interferon INF to a level comparable to that of young mice. Rb1 + Re can not only reduce the INF content, but also reduce the TNF content. The above results show that American ginseng saponin Rb1 and Re can delay the decline of the immune system in the aging model, and the combined intervention of the two is significantly better than individual intervention in the recovery of the immune system. This paper can provide theoretical basis and data support for the development of American ginseng nutritional supplements and its application in aging groups products to improve immunity.

Physicochemical and antioxidant properties of pectin from Actinidia arguta Sieb.et Zucc (A. arguta) extracted by ultrasonic.

Pectin was extracted from Actinidia arguta Sieb. et Zucc (A.arguta) using the ultrasound-assisted acid method and the single acid method. The physicochemical properties, structure, and antioxidant properties of two different pectins were investigated. The results showed that the extraction yield of the ultrasound-assisted acid method is higher than that of the single acid method. The molecular structure of A. arguta pectin extracted by the ultrasound-assisted acid method belongs to a mixed structure of RG-I and HG-type domains. Through structural feature analysis, the ultrasound-assisted extraction pectin (UAP) has a more branched structure than the single acid-extracted pectin (SAP). The SAP has a higher degree of esterification than the UAP. The physical property results show that the viscosity, solubility, and water-holding capacity of the UAP are better than those of the SAP. The antioxidant test results show that the hydroxyl radical scavenging and reducing powers of the UAP are superior to those of the SAP. This study shows the composition, physicochemical properties, and antioxidant activity of A. arguta pectin extracted by the ultrasonic-assisted extraction method to provide a theoretical basis for its application as an antioxidant and other food additives in the food industry.

Mesenchymal stem cells alleviate sepsis-induced acute lung injury by blocking neutrophil extracellular traps formation and inhibiting ferroptosis in rats.

Acute lung injury (ALI) is one of the most serious complications of sepsis, characterized by high morbidity and mortality rates. Ferroptosis has recently been reported to play an essential role in sepsis-induced ALI. Excessive neutrophil extracellular traps (NETs) formation induces exacerbated inflammation and is crucial to the development of ALI. In this study, we explored the effects of ferroptosis and NETs and observed the therapeutic function of mesenchymal stem cells (MSCs) on sepsis-induced ALI. First, we produced a cecal ligation and puncture (CLP) model of sepsis in rats. Ferrostain-1 and DNase-1 were used to inhibit ferroptosis and NETs formation separately, to confirm their effects on sepsis-induced ALI. Next, U0126 was applied to suppress the MEK/ERK signaling pathway, which is considered to be vital to NETs formation. Finally, the therapeutic effect of MSCs was observed on CLP models. The results demonstrated that both ferrostain-1 and DNase-1 application could improve sepsis-induced ALI. DNase-1 inhibited ferroptosis significantly in lung tissues, showing that ferroptosis could be regulated by NETs formation. With the inhibition of the MEK/ERK signaling pathway by U0126, NETs formation and ferroptosis in lung tissues were both reduced, and sepsis-induced ALI was improved. MSCs also had a similar protective effect against sepsis-induced ALI, not only inhibiting MEK/ERK signaling pathway-mediated NETs formation, but also alleviating ferroptosis in lung tissues. We concluded that MSCs could protect against sepsis-induced ALI by suppressing NETs formation and ferroptosis in lung tissues. In this study, we found that NETs formation and ferroptosis were both potential therapeutic targets for the treatment of sepsis-induced ALI, and provided new evidence supporting the clinical application of MSCs in sepsis-induced ALI treatment.

Effect of an educational video about ERAS on reducing preoperative anxiety and promoting recovery.

Video propaganda is reported effectively improving patients' understanding of operation. However, whether a video introducing patients' most concerns can reduce preoperative anxiety and promote recovery stays unsealed. In this study, we investigated the effects of complementary therapy of educational video during preoperative visit. The results showed that thirty-five (23.2%) parents in Group Control were diagnosed as anxiety according to SAS, and nineteen (12.3%) patients were diagnosed after video intervention. The APAIs anxiety score and APAIs information score in Group Video were lower than those in Group Control. Compared with Group Control, video visit helped to increase the first-attempt pass rate of the knowledge retention exam and solve the patient's most worried concerns, and decrease incidence of emergence agitation, total cost of hospitalization and length of hospital stay. Moreover, video visit improved satisfaction degrees of patients and their main family members. Briefly, our study demonstrated video visit can improve patients' knowledge of anesthesia and decrease their preoperative anxiety, which may represent an important complementary therapy to routine preoperative visits.

Discovery of Chiral Diamine Derivatives Containing 1,2-Diphenylethylenediamine as Novel Antiviral and Fungicidal Agents.

Severe plant virus diseases lead to poor harvests and poor crop quality, and the lack of effective suppressive drugs makes plant disease control a huge challenge. Natural product-based structural simplification is an important strategy for finding novel pesticide candidates. According to our previous research on the antiviral activities of harmine and tetrahydroharmine derivatives, a series of chiral diamine compounds were designed and synthesized by means of structural simplification using diamines in natural products as the core structure in this work, and the antiviral and fungicidal activities were investigated. Most of these compounds displayed higher antiviral activities than those of ribavirin. Compounds 1a and 4g displayed higher antiviral activities than ningnanmycin at 500 µg/mL. The antiviral mechanism research revealed that compounds 1a and 4g could inhibit virus assembly by binding to tobacco mosaic virus (TMV) CP and interfere with the assembly process of TMV CP and RNA via transmission electron microscopy and molecular docking. Further fungicidal activity tests showed that these compounds displayed broad-spectrum fungicidal activities. Compounds 3a, 3i, 5c, and 5d with excellent fungicidal activities against Fusarium oxysporum f.sp. cucumerinum can be considered as new fungicidal candidates for further research. The current work provides a reference to the development of agricultural active ingredients in crop protection.

Pyrene-based covalent organic framework for selective enrichment of hydrophobic peptides with simultaneous proteins exclusion.

Owing to the desirable structures, covalent organic frameworks (COFs) have emerged as promising porous crystalline materials in bioanalytical and biomedical science. However, the application of their merits for analysis of hydrophobic peptides in complicated bio-samples has not been well investigated, possibly due to challenges in developing materials with high-specific binding effect of target peptides and accurate controllable pore-size for high selectivity. In this study, we proposed the size-exclusive peptide enrichment with Azo-COF constructed from 1,3,6,8-tetrabromopyrene (TBPy) building block and p-azoaniline linking units. The as-synthesized sieve-like COFs show high surface area together with accessible nanometer pore size (∼2.5 nm). With these advantages, specific enrichment of hydrophobic peptides using Azo-COF can be achieved by simply packing them in a 100 µL Axygen pipette tip. A maximum capacity of 36 mg g-1 for FGFGF was obtained, which is more than a magnitude order larger than those of hydrophilic peptides. Furthermore, this method was successfully applied in analysis of hydrophobic peptides in tryptic digest of proteins and real human serum samples, indicating that the proposed method is promising for high-selective peptides enrichment from complex biological samples, and is of great value for further application of the functional materials in bioanalysis.

Discovery of Phytoalexin Camalexin and Its Derivatives as Novel Antiviral and Antiphytopathogenic-Fungus Agents.

In response to the invasion of plant viruses and pathogenic fungi, higher plants produce defensive allelochemicals. Finding candidate varieties of botanical pesticides based on allelochemicals is one of the important ways to create efficient and green pesticides. Here, a series of camalexin derivatives based on a phytoalexin camalexin scaffold were designed, synthesized, and assessed for their antiviral and fungicidal activities systematically. Most of these camalexin derivatives exhibited better antiviral activities against tobacco mosaic virus (TMV) than the control antiviral agent ribavirin. Under the same test conditions, the anti-TMV activities of compounds 3d, 5a, 5d, and 10f-10h were found to be equivalent to or better than that of ningnanmycin, an agricultural cytosine nucleoside antibiotic with excellent protective effect. The antiviral mechanism research showed that compound 5a could cause 20S CP disk fusion and disintegration, thus affecting the assembly of virus particles. The results of molecular docking indicate that there were obvious hydrogen bonds between compounds 3d, 5a, and 10f and TMV CP. The binding constants of compounds 5a and 10f to TMV CP were also calculated using fluorescence titration. These camalexin derivatives also presented broad spectrum fungicidal activities, especially for Rhizoctonia solani and Physalospora piricola. In this work, the design, synthesis, structure optimization, and mode of action of camalexin derivatives were carried out progressively. This work provides a reference for using defensive chemical compounds as novel pesticide lead compounds.

Comparison of the Curative Effect of Percutaneous Reduction with Plastic Calcaneal Forceps Combined with Medial External Fixation in the Treatment of Intra-Articular Calcaneal Fractures.

OBJECTIVE: To compare the clinical efficacy of percutaneous minimally invasive reduction combined with external fixation and a tarsal sinus approach to treat Sanders type II and III intra-articular calcaneal fractures. METHODS: The clinical data of 64 patients with Sanders type II and III calcaneal fractures admitted to our hospital from January 2010 to January 2016 were retrospectively analyzed; data includedage, sex, body mass index. According to the surgical method, they were divided into the percutaneous minimally invasive reduction with internal and external fixation group (30 cases) and the tarsal sinus approach group (34 cases).The two groups of patients were compared in terms of the time tosurgery, length of hospital stay, intraoperative blood loss, operative duration, complications, radiographic features, including the heel bone length, width, height, Bohlerangle, Gissane angle, and calcaneal varus angle, and clinical efficacy indicators, including the American Orthopedic Foot and Ankle Society (AOFAS) score, the visual analog scale (VAS) pain score, health survey profile (SF-36) score and Maryland ankle function score. RESULTS: Patients in both groups were followed up for 12 to 50 months, with an average of 24.8 months.Bony union was achieved in all cases. The time to surgery, length of hospitalstay, intraoperative blood loss and incidence of incision-related complications were significantly lower in the percutaneous minimally invasive medial external fixation group than in the tarsal sinus group (P < 0.01). At the last follow-up, the calcaneal length, width, and height, Bohler angle, Gissane angle, and varus angle were significantly increased in both groups (P < 0.01), the calcaneal width was significantly lower after than before surgery (P < 0.01), and there were no statistically significant differences between the two groups (P > 0.05). As measures of clinical efficacy, the AOFAS, VAS, SF-36 and Maryland scores were 85.28 ± 8.21, 0.84 ± 1.21, 82.95 ± 3.25 and 83.56 ± 3.32, respectively, at the last follow-up in the percutaneous minimally invasive medial external fixation group and 83.32 ± 7.69, 1.85 ± 1.32, 80.71 ± 5.42, and 81.85 ± 2.41 in the tarsal sinus group, respectively, with no significant differences between the two groups (P > 0.05). CONCLUSION: Under the condition of a good command of surgical indications and surgical skills, the use of plastic calcaneal forceps for percutaneous minimally invasive reduction combined with medial external fixation for the treatment of Sanders type II and III intra-articular calcaneal fractures can achieve similar clinical effects as the tarsal sinus approach. However, the use of plastic calcaneal forceps for percutaneous minimally invasive reduction combined with internal and external fixation has advantages, such as fewer complications, less bloodloss, and a shorter operation, and thus has good safety and is worthy of clinical promotion.

Structural Simplification of Marine Natural Products: Discovery of Hamacanthin Derivatives Containing Indole and Piperazinone as Novel Antiviral and Anti-phytopathogenic-fungus Agents.

With the increasing severity of plant diseases and the emergence of pathogen resistance, there is an urgent need for the development of new efficient and environment-friendly pesticides. Marine natural product (MNP) resources are rich and diverse. Structural simplification based on MNPs is an important strategy to find novel pesticide candidates. In this work, the marine natural product 6″-debromohamacanthin A (1a) was efficiently prepared and selected as the parent structure. A series of hamacanthin derivatives were designed, synthesized, and studied on the antiviral and antifungal activities. Most of these compounds displayed higher antiviral activities than ribavirin. The antiviral activities of compounds 1a and 13e-13h are similar to or higher than that of ningnanmycin (perhaps the most efficient anti-plant-virus agent). Compound 13h was selected for further antiviral mechanism research via transmission electron microscopy, molecular docking, and fluorescence titration. The results showed that compound 13h could bind to TMV CP and interfere with the assembly process of TMV CP and RNA. In addition, these hamacanthin derivatives also exhibited broad-spectrum inhibitory effects against eight common agricultural pathogens. Compounds 1a, 12b, and 12f with excellent fungicidal activities can be considered as new fungicidal candidates for further research. These results provide a basis for the application of hamacanthin alkaloids in crop protection.

Pityriacitrin marine alkaloids as novel antiviral and anti-phytopathogenic-fungus agents.

BACKGROUND: Plant diseases have been gripping agricultural production, seriously affecting the growth and yields of crops. Marine natural products are an important source for novel drugs discovery. In this work, pityriacitrin marine alkaloids were selected as the parent structures. A series of pityriacitrin alkaloid analogues were rationally designed, synthesized and evaluated for their antiviral activities and fungicidal activities. RESULT: Most of these compounds were demonstrated to have higher antiviral activities than ribavirin. Particularly, compounds 3a, 3e, 8f, 8g, and 9g displayed higher anti-TMV activities than ningnanmycin at 500 µg·mL-1 . Mechanism research revealed that 3a could bind to TMV CP with an excellent affinity (Ka  = 8.67 × 106 L·mol-1 ), thus interfere with the assembly of virus particles. These alkaloids also showed broad-spectrum fungicidal activities against eight kinds of phytopathogenic fungi. Compound 5f with 1.43-3.84 µg·mL-1 EC50 value against three fungi emerged as a new fungicidal candidate. CONCLUSION: Pityriacitrin alkaloids and their derivatives were synthesized and evaluated for anti-TMV and fungicidal activities for the first time. Compounds 3a and 5f with excellent activities emerged as new candidates for antiviral research and fungicidal research, respectively. Current work provided a new idea for the molecular design and development of novel plant virus and fungi inhibitors in the future. © 2021 Society of Chemical Industry.

Discovery of Cysteine and Its Derivatives as Novel Antiviral and Antifungal Agents.

Based on the structure of the natural product cysteine, a series of thiazolidine-4-carboxylic acids were designed and synthesized. All target compounds bearing thiazolidine-4-carboxylic acid were characterized by 1H-NMR, 13C-NMR, and HRMS techniques. The antiviral and antifungal activities of cysteine and its derivatives were evaluated in vitro and in vivo. The results of anti-TMV activity revealed that all compounds exhibited moderate to excellent activities against tobacco mosaic virus (TMV) at the concentration of 500 µg/mL. The compounds cysteine (1), 3-4, 7, 10, 13, 20, 23, and 24 displayed higher anti-TMV activities than the commercial plant virucide ribavirin (inhibitory rate: 40, 40, and 38% at 500 µg/mL for inactivation, curative, and protection activity in vivo, respectively), especially compound 3 (inhibitory rate: 51%, 47%, and 49% at 500 µg/mL for inactivation, curative, and protection activity in vivo, respectively) with excellent antiviral activity emerged as a new antiviral candidate. Antiviral mechanism research by TEM exhibited that compound 3 could inhibit virus assembly by aggregated the 20S protein disk. Molecular docking results revealed that compound 3 with higher antiviral activities than that of compound 24 did show stronger interaction with TMV CP. Further fungicidal activity tests against 14 kinds of phytopathogenic fungi revealed that these cysteine derivatives displayed broad-spectrum fungicidal activities. Compound 16 exhibited higher antifungal activities against Cercospora arachidicola Hori and Alternaria solani than commercial fungicides carbendazim and chlorothalonil, which emerged as a new candidate for fungicidal research.

Treatment of Thoracolumbar Fractures Through Different Short Segment Pedicle Screw Fixation Techniques: A Finite Element Analysis.

OBJECTIVE: To compare the von Mises stresses of the pedicle screw system and the displacement of injured vertebrae using 3-D finite element analysis, and to evaluate the curative effect of the pedicle screw system. METHODS: Finite element methods were used for biomechanical comparison of four posterior short segment pedicle screw fixation techniques. The different pedicle screw models are traditional trajectory (TT), Universal Spine System (USS), cortical bone trajectory (CBT), and CBT at the cranial level and pedicle screw (PS) at the caudal level (UP-CBT). The stress distribution of the screws and connecting rods under different working conditions and the displacement of the injured vertebrae were compared and analyzed. RESULTS: After the pedicle screw system was fixed, the stress under vertical compression was mainly concentrated at the proximal end of the screw, while the stress was mainly concentrated on the connecting rod during flexion, extension, lateral flexion, and rotation. The TT group had the greatest stress during the flexion, extension, and left and right rotation. The UP-CBT group was most stressed when the left and right sides were flexed; the stress of the USS screw system was less than that of the other three models during flexion, lateral flexion, and rotation. The maximum von Mises stress values of pedicle screws in all exercise states were 556.2, 340.7, 458.1, and 533.4 MPa, respectively. In the USS group, the displacement of the injured vertebra was small in the flexion, and the left and right lateral flexion and the right rotation were higher than in the TT group and the CBT group. The maximum displacements of the injured vertebrae in all motion states were 1.679, 1.604, 1.752, and 1.777 mm, respectively. CONCLUSION: Universal Spine System pedicle screws are relatively less stressed under different working conditions, the risk of breakage is small, and the model is relatively stable; CBT screws do not exhibit better mechanical properties than conventional pedicle screws and USS pedicle screws.

Discovery, Structural Optimization, and Mode of Action of Essramycin Alkaloid and Its Derivatives as Anti-Tobacco Mosaic Virus and Anti-Phytopathogenic Fungus Agents.

Plant diseases seriously affect crop yield and quality and are difficult to control. Marine natural products (MNPs) have become an important source of drug candidates with new biological mechanisms. Marine natural product essramycin (1) was found to have good anti-tobacco mosaic virus (TMV) and anti-phytopathogenic fungus activities for the first time. A series of essramycin derivatives were designed, synthesized, and evaluated for their bioactivity. Most of these compounds exhibited antiviral effects that are greater than that of the control ribavirin. Compounds 7e and 8f displayed antiviral activities that are greater than that of ningnanmycin (the most widely used antiviral agent at present), thus emerging as novel antiviral lead compounds. As the lead compound, 7e was selected for further antiviral mechanism research. The results indicated that 7e could inhibit virus assembly and promote 20S disk protein aggregation. Fungicidal activity tests against 14 kinds of phytopathogenic fungi revealed that essramycin analogues displayed broad-spectrum fungicidal activities. Compound 5b displayed more than 50% inhibition rate against most of the 14 kinds of phytopathogenic fungi at 50 µg/mL. The current research lays a solid foundation for the application of essramycin alkaloids in crop protection.

Biocompatible Porous Tantalum Metal Plates in the Treatment of Tibial Fracture.

Fractures of the tibia represent a common class of injuries in orthopedics. The blood supply to the tibia is poor due to the small subcutaneous muscle tissues inside. Consequently, the tibia is prone to delayed fracture healing and nonunion of the fracture after surgery. In this case, we used porous tantalum metal plate to treat nonunion of a tibial fracture and achieved satisfactory therapeutic effects. For the first time in the field, we used 3D printing technology to fabricate porous tantalum metal plates for the treatment of tibial fractures. The resulting porous tantalum metal exhibited excellent mechanical and biological properties, and improved the therapeutic effects for the treatment of a tibial fracture nonunion. Porous tantalum metal plates have great application potential as a new implant material for internal fixation.

SIRT1 inhibits apoptosis in in vivo and in vitro models of spinal cord injury via microRNA-494.

The aim of the present study was to investigate the function and mechanism of sirtuin 1 (SIRT1) in spinal cord injury (SCI). Reverse transcription­quantitative polymerase chain reaction was used to measure the expression levels of microRNA (miR)­494. MTT assay, lactate dehydrogenase activity assay and flow cytometry were used to analyze the effects of miR­494 on cell growth and apoptosis in a model of SCI. The present study demonstrated that SIRT1 expression was reduced; whereas miR­494 expression was increased in a rat model of SCI. Overexpression of miR­494 suppressed the protein expression levels of SIRT1, and induced p53 protein expression. Conversely, knockdown of miR­494 induced SIRT1 protein expression in an in vitro model of SCI. Furthermore, overexpression of miR­494 promoted cell apoptosis and decreased cell growth in an in vitro model of SCI; however, miR­494 knockdown enhanced cell growth and inhibited cell apoptosis. Administration of a SIRT1 agonist reduced the effects of miR­494 overexpression on cell apoptosis in an SCI model, whereas treatment with a p53 agonist reduced the effects of miR­494 knockdown on cell apoptosis in an SCI model. Together, these findings suggested that SIRT1 may inhibit apoptosis of SCI in vivo and in vitro through the p53 signaling pathway, whereas miR­494 suppressed SIRT1 and induced apoptosis.

Natural Products for Drug Discovery: Discovery of Gramines as Novel Agents against a Plant Virus.

Plant viral diseases seriously affect crop yield and quality. The natural product gramine (1) and its simple structural analogues 2-35 were synthesized from indoles, amines, and aldehydes in one step. The antiviral effects of these alkaloids were evaluated systematically. Most of these compounds were found to have higher antiviral effects than commercial ribavirin for the first time. Especially compounds 22, 30, and 31 exhibited significantly higher effects than ningnanmycin, thereby emerging as novel antiviral leads for further optimization. The preliminary implementation indicated that these compounds likely inhibit the assembly of tobacco mosaic virus (TMV) by cross-linking TMV capsid protein. Gramine analogues were also found to have broad-spectrum fungicidal effects. Although gramine has been reported to have influence on germination and development of Erysiphe graminis, these compounds displayed no fungicidal effects against Blumeria graminis f. sp. tritici on wheat in our test. Some of these compounds also exhibited certain insecticidal activities.

Il34-Csf1r Pathway Regulates the Migration and Colonization of Microglial Precursors.

Microglia are the major immune cells in the central nervous system (CNS). Born in peripheral hematopoietic tissues, microglial precursors colonize the CNS during early embryogenesis and maintain themselves thereafter. However, the mechanism underlying this colonization process remains elusive. We have recently demonstrated that neuronal apoptosis contributes to microglia colonization in zebrafish. Here, we further show that prior to neuronal apoptosis, microglial precursors are attracted to the proximal brain regions by brain-derived interleukin 34 (il34) and its receptor colony-stimulating factor 1 receptor a (csf1ra). In both il34- and csf1ra-deficient zebrafish larva, embryonic macrophages fail to migrate to the anterior head and colonize the CNS, but their initial development and colonization to peripheral tissues remain largely unaffected. Activation of Il34-Csf1ra pathway is sufficient to attract embryonic macrophages to the CNS independent of neuronal apoptosis. Our study shows that cytokine signaling and neuronal apoptosis synergistically orchestrate the colonization of microglia in early zebrafish development.

Adult zebrafish Langerhans cells arise from hematopoietic stem/progenitor cells.

The origin of Langerhans cells (LCs), which are skin epidermis-resident macrophages, remains unclear. Current lineage tracing of LCs largely relies on the promoter-Cre-LoxP system, which often gives rise to contradictory conclusions with different promoters. Thus, reinvestigation with an improved tracing method is necessary. Here, using a laser-mediated temporal-spatial resolved cell labeling method, we demonstrated that most adult LCs originated from the ventral wall of the dorsal aorta (VDA), an equivalent to the mouse aorta, gonads, and mesonephros (AGM), where both hematopoietic stem cells (HSCs) and non-HSC progenitors are generated. Further fine-fate mapping analysis revealed that the appearance of LCs in adult zebrafish was correlated with the development of HSCs, but not T cell progenitors. Finally, we showed that the appearance of tissue-resident macrophages in the brain, liver, heart, and gut of adult zebrafish was also correlated with HSCs. Thus, the results of our study challenged the EMP-origin theory for LCs.

[Conservative methods for osteonecrosis of the femoral head: the review of 1005 cases].

OBJECTIVE: To research on the conservative methods used to preserve the femoral head of patients with osteonecrosis of the femoral head. METHODS: In these series surgical procedures the osteonecrotic lesion was removed and various vascularized bone blocks or periosteal flaps with its nutrient vessels were transferred to regain sphericity of the femoral head and reinforce the sequestrum. The current study assessed 1005 patients (1226 hips) operated on from 1989 to 2002 with an average follow-up of 5.1 years (range, 1.5-15 years). The mean age of the patients was 37.4 years (range, 17-65 years). RESULTS: Sixty-one hips (57 patients) had conversion surgery to a total hip arthroplasty because of progressive collapse or severe pain, or both. In the patients without failure, postoperative Harris hip score improved significantly. Of the 1174 reconstructions that were in situ, 1041 (89.4%) were clinically successful, and 878 (75.4%) were radiologically successful. In relation to the stage of necrosis according to the classification system of Ficat and Alert, good results were achieved in 95.3% of the patients with stages II disease, 87.9% with stages III and 60.8% with stages IV. CONCLUSIONS: Conservative methods of vascularized bone block or periosteal flap transfer should be considered in active symptomatic patients to preserve the femoral head. In addition, the earlier the stages of the disease the better outcome could be obtained.