Effectiveness and safety of the ablative fractional 2940-nm Er: YAG laser for the treatment of androgenetic alopecia.

Laser sources have established their potential effect in inducing hair regrowth. No large cohort study has evaluated the effect of ablative fractional 2940-nm erbium yttrium aluminum garnet (Er: YAG) laser in the treatment of androgenetic alopecia (AGA). To investigate the efficacy and safety of the ablative fractional 2940-nm Er: YAG laser in combination with medication therapy for the treatment of AGA. We performed a retrospective study between first July 2021 to 30th December 2021. All included patients received oral finasteride and topical minoxidil, or combined with six sessions of Er: YAG laser at 2-week intervals. Patients were divided into medication or combined therapy groups. The efficacy of the two therapies was evaluated by the investigator's Global Assessment (IGA) scores and the patient's Likert satisfaction scale at week 12 and week 24. Changes in total, terminal and villous hair count, total and terminal hair diameter, and AGA grade were also recorded. Adverse events were evaluated at each follow-up. A total of 192 male patients with AGA were included, including 67 receiving combination treatment, and 125 receiving medication treatment. At week 24, the combination treatment afforded superior outcomes in the IGA score, patient's global assessment, total and terminal hair counts, and diameters (all P<0.05). No severe adverse events were reported in both groups. The combined therapy of ablative fractional Er: YAG laser and medication was superior in treating male AGA than single medication therapy without serious adverse effects.

Association of osteoporotic fractures of femoral neck and femoral neck geometric parameters in native Chinese women.

BACKGROUND: Although it is generally believed that the femoral neck fracture is related to the femoral neck geometric parameters (FNGPs), the association between the risk of osteoporotic fracture of the femoral neck and FNGPs in native Chinese women is still unclear. METHODS: A total of 374 female patients (mean age 70.2 ± 9.32 years) with osteoporotic fracture of the femoral neck, and 374 non-fracture control groups were completely matched with the case group according to the age ratio of 1:1. Using DXA bone densitometer to measured eight FNGPs: the outer diameter (OD), cross-sectional area (CSA), cortical thickness (CT), endocortical diameter (ED), buckling ratio (BR), section modulus (SM), cross-sectional moment of inertia (CSMI), and compressive strength index (CSI) at the narrowest point of the femoral neck. RESULTS: Compared with the control group, the average values of OD (2.9%), ED (4.5%), and BR (26.1%) in the patient group significantly increased (p = 0.015 to < 0.001), while CSA (‒15.3%), CT (‒18.2%), SM (‒10.3%), CSMI (‒6.4%), and CSI (‒10.8%) significantly decreased (all p < 0.001). The prevalence of osteoporosis in the lumbar spine, femoral neck, and total hip was, respectively, 82%, 81%, and 65% in fracture patients. Cox proportional hazard model analysis showed that in the age adjusted model, the fracture hazard ratio (HR) of CSA, CT, BR, SM, and CSI significantly increased (HRs = 1.60‒8.33; 95% CI = 1.08‒16.6; all p < 0.001). In the model adjusted for age and femoral neck BMD, HRs of CT (HRs = 3.90‒8.03; 95% CI = 2.45‒15.1; all p < 0.001) and BR (HRs = 1.62‒2.60; 95% CI = 1.20‒5.44; all p < 0.001) were still significantly increased. CONCLUSION: These results suggest that the majority of osteoporotic fractures of the femoral neck of native Chinese women occur in patients with osteoporosis. CT thinning or BR increase of FNGPs may be independent predictors of fragility fracture of femoral neck in native Chinese women unrelated to BMD.

Crown ether-like octanuclear molybdenum(V) clusters for cation binding and gas adsorption.

Octanuclear polyoxomolybdenum-based porous materials, Na8[Mo8O8(µ2-O)8(µ2-OH)8(3-apz)4]2·26H2O (1, 3-Hapz = 3-aminopyrazole), K8[Mo8O8(µ2-O)8(µ2-OH)8(3-apz)4]2·7H2O (2) and (NH4)4[Mo8O8(µ2-O)8(µ2-OH)4(3-apz)8]·20.5H2O (3), have been successfully synthesized by a hydrothermal method and fully characterized. X-ray structural analyses show that microporous materials 1-3 contain round pores formed by octanuclear molybdenum-oxygen groups connected sequentially with pore sizes of 4.0, 4.0, and 4.8 Å, respectively. Both 1 and 2 are composed of two {Mo8} rings, which are connected by strong intramolecular hydrogen bonds between bridging hydroxy groups and oxygen atoms to form dimeric structures. The central pores in 1 and 2 are occupied by Na+ and K+, respectively, while they are empty in 3. This reflects the structural expansion and contraction effects induced by different cations. Through intermolecular stacking, 1-3 also exhibit channels with sizes of 14.0 × 6.4, 4.6 × 2.6, and 5.4 × 5.4 Å, respectively, which were used for the studies of gas adsorption. The results show that 1-3 can selectively adsorb CO2 and O2, including the empty hole in 3, while they show little or no affinity for gases H2, N2, and CH4. Moreover, an additional polyoxomolybdenum-based species (Mo8O26)n·4n(3-H2apz) (4) has been obtained with protonated 3-aminopyrazole in the absence of a reducing agent, which can serve as an intermediate for the polyoxomolybdenum-based porous products.

P75NTR+CD64+ neutrophils promote sepsis-induced acute lung injury.

Patients suffering from sepsis-induced acute lung injury (ALI) exhibit a high mortality rate, and their prognosis is closely associated with infiltration of neutrophils into the lungs. In this study, we found a significant elevation of CD64+ neutrophils, which highly expressed p75 neurotrophin receptor (p75NTR) in peripheral blood of mice and patients with sepsis-induced ALI. p75NTR+CD64+ neutrophils were also abundantly expressed in the lung of ALI mice induced by lipopolysaccharide. Conditional knock-out of the myeloid lineage's p75NTR gene improved the survival rates, attenuated lung tissue inflammation, reduced neutrophil infiltration and enhanced the phagocytic functions of CD64+ neutrophils. In vitro, p75NTR+CD64+ neutrophils exhibited an upregulation and compromised phagocytic activity in blood samples of ALI patients. Blocking p75NTR activity by soluble p75NTR extracellular domain peptide (p75ECD-Fc) boosted CD64+ neutrophils phagocytic activity and reduced inflammatory cytokine production via regulation of the NF-κB activity. The findings strongly indicate that p75NTR+CD64+ neutrophils are a novel pathogenic neutrophil subpopulation promoting sepsis-induced ALI.

Laser acupuncture and photobiomodulation therapy in Bell's palsy with a duration of greater than 8 weeks: a randomized controlled trial.

To investigate the efficacy of laser acupuncture and photobiomodulation therapy in alleviating symptoms among patients diagnosed with Bell's palsy with duration of greater than 8 weeks. The randomized controlled trial has been performed from May 2021 to April 2023. Patients were eligible who had Bell's palsy with duration of greater than 8 weeks on out-patient Department of Otorhinolaryngology in Beijing Tongren Hospital. The laser acupuncture group received class IV laser treatment for 3 times per weeks, a total of 72 times. The control group received the same treatment procedure except the laser parameter. The primary outcome measures comprised House-Brackmann facial nerve grading system and electroneurography. Secondary outcome measures comprised Sunnybrook facial grading system, electromyography, and the blink reflex. A total of 84 participants were included (42 control group, 42 laser acupuncture group). After treatment, House-Brackmann facial nerve grading system (OR, 0.11; 95% CI, 0.04-0.30; P < 0.001), and the pathologic numbers of electroneuronography were statistically different between the laser acupuncture group and control group, including orbicularis oculi (OR,0.08; 95% CI, 0.02-0.21; P < 0.001), Frontalis muscle (OR,0.14; 95% CI, 0.05-0.39; P < 0.001), Orbicularis oris (OR,0.13; 95% CI, 0.04-0.36; P < 0.001), Ala nasi muscle (OR,0.06; 95% CI, 0.02-0.18; P < 0.001). In secondary outcomes, Sunnybrook facial grading system, has significant difference between the two groups (20.26; 95% CI, 14.69 to 25.83; P < 0.01). Latency by ENoG, include orbicularis oculi (-0.61; 95% CI, -0.43 to -0.09; P < 0.001), frontalis muscle (-0.12; 95% CI, -0.21 to -0.03; P < 0.01), orbicularis oris (-0.28; 95% CI, -0.41 to -0.16; P < 0.001), and ala nasi muscle (-0.26; 95% CI, -0.38 to -0.16; P < 0.001). All amplitudes of MUAPs and durations by electromyography (EMG) showed statistically significant differences compared with the control group after treatment. For the frontalis muscle, the amplitude of MUAPs was -64.23 (95% CI, -80.89 to -47.56; P < 0.001) and duration was -1.18 (95% CI, -1.49 to -0.87; P < 0.001). For orbicularis oris, amplitude of MUAPs was -29.82 (95% CI, -55.03 to -4.62; P = 0.02) and duration was -0.57 (95% CI, -0.94 to -0.20; P < 0.001). For depressor angulli oris, amplitude of MUAPs was -47.06 (95% CI, -62.15 to -31.97; P < 0.001) and duration was -2.21 (95% CI, -2.69 to -1.72; P < 0.001). Blink reflex, including R1 (OR, 0.03; 95% CI, 0.01-0.16; P < .001), R2 (OR, 0.04; 95% CI, 0.004-0.29; P < .001), and R2 latency differences (OR, 0.15; 95% CI, 0.05-0.51; P < .001), have significant difference between the two groups, respectively. The findings suggest that laser acupuncture relieve symptoms for patients with Bell's palsy with a duration of greater than 8 weeks.Trial registration: ClinicalTrials.gov Identifier: NCT05846217.

ProBDNF contributed to patrolling monocyte infiltration and renal damage in systemic lupus erythematosus.

Monocyte aberrations have been increasingly recognized as contributors to renal damage in systemic lupus erythematosus (SLE), however, recognition of the underlying mechanisms and modulating strategies is at an early stage. Our studies have demonstrated that brain-derived neurotrophic factor precursor (proBDNF) drives the progress of SLE by perturbing antibody-secreting B cells, and proBDNF facilitates pro-inflammatory responses in monocytes. By utilizing peripheral blood from patients with SLE, GEO database and spontaneous MRL/lpr lupus mice, we demonstrated in the present study that CX3CR1+ patrolling monocytes (PMo) numbers were decreased in SLE. ProBDNF was specifically expressed in CX3CR1+ PMo and was closely correlated with disease activity and the degree of renal injury in SLE patients. In MRL/lpr mice, elevated proBDNF was found in circulating PMo and the kidney, and blockade of proBDNF restored the balance of circulating and kidney-infiltrating PMo. This blockade also led to the reversal of pro-inflammatory responses in monocytes and a noticeable improvement in renal damage in lupus mice. Overall, the results indicate that the upregulation of proBDNF in PMo plays a crucial role in their infiltration into the kidney, thereby contributing to nephritis in SLE. Targeting of proBDNF offers a potential therapeutic role in modulating monocyte-driven renal damage in SLE.

Iodine-Catalyzed Regioselective Synthesis of Diphenyl-Substituted Carbazoles via [4 + 2] Annulation of ß-Formyl Ketones with Indoles.

The [4 + 2] annulation of ß-formyl ketones with an indole has been developed for the regioselective synthesis of diphenyl-substituted carbazoles in the presence of a catalytic amount of iodine. The 1,4-dicarbonyl compound containing a phenyl group at the α-position of an aldehyde group reacts more readily with indoles to form carbazole derivatives. Using this method, a variety of carbazole derivatives can be readily accessed under mild reaction conditions.

Comparison of 1064-nm Nd:YAG picosecond laser using fractional micro-lens array vs. ablative fractional 2940-nm Er:YAG laser for the treatment of atrophic acne scar in Asians: a 20-week prospective, randomized, split-face, controlled pilot study.

Background: The 1064-nm Nd:YAG picosecond lasers using fractional micro-lens array (P-MLA) was a promising therapy for skin resurfacing. However, no studies have compared P-MLA with ablative fractional 2940-nm Er:YAG lasers (AF-Er) in the treatment of atrophic acne scars. Objectives: To evaluate the efficacy and safety of P-MLA and AF-Er for the treatment of atrophic acne scars. Methods: We performed a prospective, randomized, split-face, controlled pilot study. Thirty-one Asian patients with mild to moderate atrophic acne scars underwent four consecutive sessions of randomized split-face treatment with P-MLA and AF-Fr at 4-week intervals. The efficacy of the two devices were evaluated by Echelle d'Evaluation Clinique des Cicatrices d'acne (ECCA) grading scale, Investigator's Global Assessment (IGA) score and patient's satisfaction. VISIA analysis was also performed to evaluate the pore and skin texture. Adverse events were recorded at each follow-up. Results: The P-MLA afforded comparable clinical responses in scar appearance as AF-Er based on the investigator's assessments (ECCA percent reduction: 39.11% vs. 43.73%; IGA score: 2.97 ± 0.65 vs. 3.16 ± 0.68; P > 0.05 for both). However, the result of patient satisfaction indicated the AF-Er-treated side achieved a slightly greater improvement in scar appearance (3.97 ± 0.78 vs. 3.55 ± 0.71; P < 0.05). Overall, the two devices did not differ largely in terms of efficacy. VISIA analysis revealed similar changing patterns of the pore and skin texture between two devices. For safety profiles, no serious side effects were reported on both sides. The P-MLA showed lower pain level, shortened duration of crust shed and edema, and less occurrence of PIH (P < 0.05 for all). Conclusion: Compared with AF-Er, P-MLA afforded comparable effect and more safety profiles in treating atrophic acne scars in Asian patients. Clinical trial registration: ClinicalTrials.gov, identifier NCT05686603.

The co-expression pattern of VEGFR-2 with indicators related to proliferation, apoptosis, and differentiation of anagen hair follicles.

An increasing number of studies show that vascular endothelial growth factor is an important regulator of hair growth, and involves in processes of hair follicle development by vascularization. Recently, VEGF receptor-2 (VEGFR-2) has been detected in epithelial cells of hair follicles, indicating that it may have a direct role in the biological activity of hair follicles. To explore how VEGFR-2 regulates hair follicle development, we investigated the co-expression pattern of VEGFR-2 with ß-catenin, Bax, Bcl-2, involucrin, AE13 (hair cortex cytokeratin), keratin 16, keratin 14, and Laminin 5 by immunofluorescence double staining in anagen hair follicles of normal human scalp skin. The results of double staining immunofluorescence showed a strong overlapping and similar expression pattern for VEGFR-2 with ß-catenin and Bcl-2, and revealing associated expression pattern with involucrin, AE13, keratin 14, keratin 16, and Laminin 5. These results elucidated that VEGFR-2 activation may participate in hair follicle differentiation, proliferation, and apoptosis in vivo.

A Nonrandomized Trial of the Effects of Near-Infrared Photobiomodulation Therapy on Bell's Palsy with a Duration of Greater Than 8 Weeks.

Objective: To determine whether photobiomodulation therapy (PBMT) by class IV Multiwave Locked System laser treatment as an adjunctive therapy could relieve symptoms in patients with Bell's palsy with a duration of greater than 8 weeks. Materials and methods: This nonrandomized controlled trial was conducted from January 2020 to December 2022. Patients were eligible if they had Bell's palsy with a duration of greater than 8 weeks at the out-patient department of otorhinolaryngology in Beijing Tongren Hospital. The control group consisted of patients recruited between January 1, 2020, and December 31, 2020. The PBMT group consisted of patients recruited between January 1, 2021, and December 31, 2022. In this study, the PBM used has a wavelength of 808 and 905 nm, 1.2 W power (808 nm is 1 W, 905 nm is 200 mW), continuous mode emission (808 nm) and pulsed mode emission (905 nm), 8.35 J/cm2 dosimetry, administered 3 times per week, 72 times of total treatment. The primary outcome measures included the House-Brackmann facial nerve grading system, the Sunnybrook facial grading system, and the Facial Clinimetric Evaluation Scale (FaCE). Secondary outcome measures comprised electroneurography, electromyography, and the blink reflex. Results: A total of 54 participants were included (27 in the control group and 27 in the photobiomodulation group). After 6 months, the House-Brackmann grading system [risk difference, -0.59, confidence interval (95% CI), -0.81 to -0.38, relative risk, 0.27, 95% CI, 0.13-0.56, p < 0.001], Sunnybrook facial grading system (21.14, 95% CI, 11.71-30.58; p < 0.001), and FaCE (-0.20, 95% CI, 0.41-0.02; p = 0.07) had significant difference between the two groups. Latency of ala nasi muscle (10.92, 95% CI, 5.58-16.27; p < 0.001) was not statistically significant after treatment compared with the control group; however, most of the electrophysiological examinations have significant difference between the two groups, respectively. Conclusions: The results of this study suggest that PBMT may relieve symptoms for patients with Bell's palsy with a duration of greater than 8 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT05585333.

Machine learning algorithms to predict risk of postoperative pneumonia in elderly with hip fracture.

BACKGROUND: Hip fracture (HF) is one of the most common fractures in the elderly and is significantly associated with high mortality and unfavorable prognosis. Postoperative pneumonia (POP), the most common postoperative complication of HF, can seriously affect patient prognosis and increase the burden on the healthcare system. The aim of this study was to develop machine learning models for identifying elderly patients at high risk of pneumonia after hip fracture surgery. METHODS: From May 2016 to November 2022, patients admitted to a single central hospital for HF served as the study population. We extracted data that could be collected within 24 h of patient admission. The dataset was divided into training and validation sets according to 70:30. Based on the screened risk factors, prediction models were developed using seven machine learning algorithms, namely CART, GBM, KNN, LR, NNet, RF, and XGBoost, and their performance was evaluated. RESULTS: Eight hundred five patients were finally included in the analysis and 75 (9.3%) patients suffered from POP. Age, CI, COPD, WBC, HB, GLU, STB, GLOB, Ka+ which are used as features to build machine learning models. By evaluating the model's AUC value, accuracy, sensitivity, specificity, Kappa value, MCC value, Brier score value, calibration curve, and DCA curve, the model constructed by XGBoost algorithm has the best and near-perfect performance. CONCLUSION: The machine learning model we created is ideal for detecting elderly patients at high risk of POP after HF at an early stage.

Altered methionine metabolism impacts phenylpropanoid production and plant development in Arabidopsis thaliana.

Phenylpropanoids are specialized metabolites derived from phenylalanine. Glucosinolates are defense compounds derived mainly from methionine and tryptophan in Arabidopsis. It was previously shown that the phenylpropanoid pathway and glucosinolate production are metabolically linked. The accumulation of indole-3-acetaldoxime (IAOx), the precursor of tryptophan-derived glucosinolates, represses phenylpropanoid biosynthesis through accelerated degradation of phenylalanine-ammonia lyase (PAL). As PAL functions at the entry point of the phenylpropanoid pathway which produces indispensable specialized metabolites such as lignin, aldoxime-mediated phenylpropanoid repression is detrimental to plant survival. Although methionine-derived glucosinolates in Arabidopsis are abundant, any impact of aliphatic aldoximes (AAOx) derived from aliphatic amino acids such as methionine on phenylpropanoid production remains unclear. Here, we investigate the impact of AAOx accumulation on phenylpropanoid production using Arabidopsis aldoxime mutants, ref2 and ref5 . REF2 and REF5 metabolize aldoximes to respective nitrile oxides redundantly, but with different substrate specificities. ref2 and ref5 mutants have decreased phenylpropanoid contents due to the accumulation of aldoximes. As REF2 and REF5 have high substrate specificity toward AAOx and IAOx respectively, it was assumed that ref2 accumulates AAOx, not IAOx. Our study indicates that ref2 accumulates both AAOx and IAOx. Removing IAOx partially restored phenylpropanoid production in ref2 , but not to the wild-type level. However, when AAOx biosynthesis was silenced, phenylpropanoid production and PAL activity in ref2 were completely restored, suggesting an inhibitory effect of AAOx on phenylpropanoid production. Further feeding studies revealed that the abnormal growth phenotype commonly observed in Arabidopsis mutants lacking AAOx production is a consequence of methionine accumulation. Significance Statement: Aliphatic aldoximes are precursors of various specialized metabolites including defense compounds. This study reveals that aliphatic aldoximes repress phenylpropanoid production and that altered methionine metabolism affects plant growth and development. As phenylpropanoids include vital metabolites such as lignin, a major sink of fixed carbon, this metabolic link may contribute to available resource allocation during defense.

Association of follicle-stimulating hormone with bone turnover markers and bone mineral density in Chinese women across the menopausal transition.

BACKGROUND: Elevated follicle-stimulating hormone (FSH) is associated with an increased risk of postmenopausal osteoporosis. This study investigated the association of serum FSH with bone turnover markers (BTMs) and bone mineral density (BMD) in healthy women undergoing menopausal transition. METHODS: A total of 487 healthy women (age 35-65 years, 50 ± 8.5 years) were enrolled in this study. Serum FSH, BTMs, and BMD at lumbar spine and total hip were measured in these subjects. RESULTS: Follicle-stimulating hormone was positively correlated with various BTMs (r = 0.339-0.583, all p < 0.001) and negatively correlated with lumbar spine and total hip BMD (r = -0.629 and -0.514, all p < 0.001). After adjusting for age and body mass index, the partial correlation coefficients of FSH with BTMs and BMD remained significant. Estimating from the regression equation, for every 10 IU/L increase in serum FSH, BTMs increased by 0.38-3.6 units, and BMD decreased by 0.03-0.05 g/cm2 , respectively. Multiple linear regression analysis showed that FSH was a positive factor for serum bone-specific alkaline phosphatase, osteocalcin, and N-telopeptide of collagen type 1 (ß = 0.188-0.403, all p < 0.001), and a negative factor for lumbar spine BMD and serum C-telopeptide of collagen type 1 (ß = -0.629 and -0.183, all p < 0.001). CONCLUSIONS: This study suggests that serum FSH levels are an independent risk factor for BTMs and BMD in menopause-transitioning women, particularly for serum BAP and lumbar spine BMD.

Altered methionine metabolism impacts phenylpropanoid production and plant development in Arabidopsis thaliana.

Phenylpropanoids are specialized metabolites derived from phenylalanine. Glucosinolates are defense compounds derived mainly from methionine and tryptophan in Arabidopsis. It was previously shown that the phenylpropanoid pathway and glucosinolate production are metabolically linked. The accumulation of indole-3-acetaldoxime (IAOx), the precursor of tryptophan-derived glucosinolates, represses phenylpropanoid biosynthesis through accelerated degradation of phenylalanine ammonia lyase (PAL). As PAL functions at the entry point of the phenylpropanoid pathway, which produces indispensable specialized metabolites such as lignin, aldoxime-mediated phenylpropanoid repression is detrimental to plant survival. Although methionine-derived glucosinolates in Arabidopsis are abundant, any impact of aliphatic aldoximes (AAOx) derived from aliphatic amino acids such as methionine on phenylpropanoid production remains unclear. Here, we investigate the impact of AAOx accumulation on phenylpropanoid production using Arabidopsis aldoxime mutants, ref2 and ref5. REF2 and REF5 metabolize aldoximes to respective nitrile oxides redundantly, but with different substrate specificities. ref2 and ref5 mutants have decreased phenylpropanoid contents due to the accumulation of aldoximes. As REF2 and REF5 have high substrate specificity toward AAOx and IAOx, respectively, it was assumed that ref2 accumulates AAOx, not IAOx. Our study indicates that ref2 accumulates both AAOx and IAOx. Removing IAOx partially restored phenylpropanoid content in ref2, but not to the wild-type level. However, when AAOx biosynthesis was silenced, phenylpropanoid production and PAL activity in ref2 were completely restored, suggesting an inhibitory effect of AAOx on phenylpropanoid production. Further feeding studies revealed that the abnormal growth phenotype commonly observed in Arabidopsis mutants lacking AAOx production is a consequence of methionine accumulation.

ProBDNF and its receptors in immune-mediated inflammatory diseases: novel insights into the regulation of metabolism and mitochondria.

Immune-mediated inflammatory diseases (IMIDs) consist of a common and clinically diverse group of diseases. Despite remarkable progress in the past two decades, no remission is observed in a large number of patients, and no effective treatments have been developed to prevent organ and tissue damage. Brain-derived neurotrophic factor precursor (proBDNF) and receptors, such as p75 neurotrophin receptor (p75NTR) and sortilin, have been proposed to mediate intracellular metabolism and mitochondrial function to regulate the progression of several IMIDs. Here, the regulatory role of proBDNF and its receptors in seven typical IMIDs, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, allergic asthma, type I diabetes, vasculitis, and inflammatory bowel diseases, was investigated.

Platelets reprogram monocyte functions by secreting MMP-9 to benefit postoperative outcomes following acute aortic dissection.

Platelets have a great ability to modulate immune responses. Monocyte-platelet aggregates (MPAs) are associated with the pathogenesis of cardiac disease. Notably, a low preoperative platelet count often indicates poor postoperative recovery following acute aortic dissection (AAD). The functions of platelets and MPAs in AAD, however, remain poorly understood. We found that, despite decreased platelet counts, platelets were also activated in AAD patients, with significant alterations in immune-modulating mediators. Of interest, monocytes in AAD patients had a suppressed immune status, which was correlated with poor outcomes following surgery. Interestingly, platelets preferentially aggregated with monocytes, and the levels of MPAs were related to recovery after surgical repair in AAD patients. Platelets restored suppressed monocyte functions in AAD patients by forming aggregates and partly by secreting matrix metalloproteinase-9 (MMP-9). Thus, the results point to a previously unknown mechanism for platelets involving monocyte reprogramming, which may improve postoperative outcomes following complex cardiovascular surgery.

Brain-Derived Neurotrophic Factor Precursor Contributes to a Proinflammatory Program in Monocytes/Macrophages After Acute Myocardial Infarction.

Background The imbalance of monocyte/macrophage polarization toward the preferential proinflammatory phenotype and a lack of normal inflammation resolution are present in acute myocardial infarction (AMI). Our previous study showed that upregulation of brain-derived neurotrophic factor precursor (proBDNF) in M2-like monocytes may contribute to the proinflammatory response in the Stanford type-A acute aortic dissection. The present study aimed to investigate the role of proBDNF signaling in monocytes/macrophages in the progress of AMI. Methods and Results We observed the upregulation of proBDNF in the proinflammatory monocytes of patients with AMI. The upregulation of proBDNF was also observed in the circulating proinflammatory Ly6Chigh monocytes and cardiac F4/80+CD86+ macrophages 3 days after AMI in a mice model. To neutralize proBDNF, the mice subjected to AMI were injected intraperitoneally with a monoclonal anti-proBDNF antibody. Echocardiography, 2,3,5-triphenyltetrazolium chloride staining, and positron emission tomography/computed tomography results demonstrate that monoclonal anti-proBDNF antibody treatment further impaired cardiac functions, increased infarct size, and exacerbated the proinflammatory state. Moreover, the level of proinflammatory Ly6Chigh in the blood and F4/80+CD86+ in the heart was further increased in monoclonal anti-proBDNF antibody mice. RNA sequencing revealed that matrix metalloprotease-9 protein level was dramatically increased, along with the activated proinflammatory-related cytokines. Matrix metalloprotease-9 inhibitor treatment attenuated the deteriorated effect of monoclonal anti-proBDNF antibody on cardiac function and infarct areas. Conclusions Our study shows that endogenous proBDNF in monocytes/macrophages may exert protective roles in cardiac remodeling after AMI by regulating matrix metalloprotease-9 activity.

Co-Expression Pattern of Artemis Serine 516 Phosphorylation with Indicators Involving in Differentiation, Proliferation and Apoptosis of Human Anagen Hair Follicles: An Immunofluorescence Double-Staining Study.

BACKGROUND: Artemis belongs to the SNM1 gene family, and plays a role in repairing ionizing-radiation-induced DNA double-strand breaks and variable (diversity) joining recombination. S534, S538, S516, S645 represent four most rapid phosphorylation sites in Artemis, and serine phosphorylation at amino acid 516 is closely associated with activation. Artemis mutation is perceived as contributing to Omenn syndrome, which manifest features of severe combined immunodeficiency disease, associated with lymphadenopathy, hepatosplenomegaly, erythroderma and baldness. In addition, Artemis phosphorylated at serine 516 (Artemis S516-P) was expressed in scalp hair follicles (HF) as well as other skin appendages, and its expression level is important to mouse hair cycling. However, whether Artemis participated in the regulation of HF growth still unclear. METHODS: Using immunofluorescence double-staining, we assessed the association between Artemis S516-P with proliferation, apoptosis, and differentiation markers in normal adult anagen scalp HF. RESULTS: The results of double-staining immunofluorescence revealed overlapping expression pattern for Artemis S516-P and keratin16, similar pattern for c-myc and p21, while presenting opposite trends for keratin 10, phospho-p53, Bax, Bcl-2 and keratin 14. CONCLUSIONS: Our study provides the clues that Artemis may play roles in regulation of differentiation, proliferation, apoptosis and cell cycling during HF growth and development.

Metabolic link between auxin production and specialized metabolites in Sorghum bicolor.

Aldoximes are amino acid derivatives that serve as intermediates for numerous specialized metabolites including cyanogenic glycosides, glucosinolates, and auxins. Aldoxime formation is mainly catalyzed by cytochrome P450 monooxygenases of the 79 family (CYP79s) that can have broad or narrow substrate specificity. Except for SbCYP79A1, aldoxime biosynthetic enzymes in the cereal sorghum (Sorghum bicolor) have not been characterized. This study identified nine CYP79-encoding genes in the genome of sorghum. A phylogenetic analysis of CYP79 showed that SbCYP79A61 formed a subclade with maize ZmCYP79A61, previously characterized to be involved in aldoxime biosynthesis. Functional characterization of this sorghum enzyme using transient expression in Nicotiana benthamiana and stable overexpression in Arabidopsis thaliana revealed that SbCYP79A61 catalyzes the production of phenylacetaldoxime (PAOx) from phenylalanine but, unlike the maize enzyme, displays no detectable activity against tryptophan. Additionally, targeted metabolite analysis after stable isotope feeding assays revealed that PAOx can serve as a precursor of phenylacetic acid (PAA) in sorghum and identified benzyl cyanide as an intermediate of PAOx-derived PAA biosynthesis in both sorghum and maize. Taken together, our results demonstrate that SbCYP79A61 produces PAOx in sorghum and may serve in the biosynthesis of other nitrogen-containing phenylalanine-derived metabolites involved in mediating biotic and abiotic stresses.