Lapagyl mitigates UV-induced inflammation and immunosuppression via Foxp3+ Tregs and CCL pathway: A single-cell transcriptomics study.

BACKGROUND: As the largest organ of the body, the skin is constantly subjected to ultraviolet radiation (UVR), leading to inflammations and changes that mirror those seen in chronological aging. Although various small molecule drugs have been explored for treating skin photoaging, they typically suffer from low stability and a high incidence of adverse reactions. Consequently, the continued investigation of photoaging treatments, particularly those utilizing herbal products, remains a critical clinical endeavor. One such herbal product, Lapagyl, is derived from the bark of the lapacho tree and possesses antioxidant efficacies that could be beneficial in combating skin photoaging. PURPOSE: This research aimed to evaluate the efficacy of the herbal product Lapagyl in combating UVR-induced skin photoaging. Additionally, it sought to unravel the mechanisms by which Lapagyl promotes the regeneration of the skin extracellular matrix. METHODS: To investigate whether Lapagyl can alleviate skin aging and damage, a UVR radiation model was established using SKH-1 hairless mice. The dorsal skins of these mice were evaluated for wrinkle formation, texture, moisture, transepidermal water loss (TEWL), and elasticity. Pathological assessments were conducted to determine Lapagyl's efficacy. Additionally, single-cell sequencing and spectrum analysis were employed to elucidate the working mechanisms and primary components of Lapagyl in addressing UVR-induced skin aging and injury. RESULTS: Lapagyl markedly reduced UVR-induced wrinkles, moisture loss, and elasticity decrease in SKH-1 mice. Single-cell sequencing demonstrated that Lapagyl corrected the imbalance in cell proportions caused by UVR, decreased UVR-induced ROS expression, and protected basal and spinous cells from skin damage. Additionally, Lapagyl effectively prevented the entry of inflammatory cells into the skin by reducing CCL8 expression and curtailed the UVR-induced formation of Foxp3+ regulatory T cells (Tregs) in the skin. Both pathological assessments and ex vivo skin model results demonstrated that Lapagyl effectively reduced UVR-induced damage to collagen and elastin. Spectrum analysis identified Salidroside as the primary compound remaining in the skin following Lapagyl treatment. Taken together, our study elucidated the skin protection mechanism of the herbal product Lapagyl against UVR damage at the cellular level, revealing its immunomodulatory effects, with salidroside identified as the primary active compound for skin. CONCLUSION: Our study provided a thorough evaluation of Lapagyl's protective effects on skin against UVR damage, delving into the mechanisms at the cellular level. We discovered that Lapagyl mitigates skin inflammation and immunosuppression by regulating Foxp3+ Tregs and the CCL pathway. These insights indicate that Lapagyl has potential as a novel therapeutic option for addressing skin photoaging.

Establishment and application of perceived age prediction model for the periocular aging research of Chinese Han women.

BACKGROUND: The assessment of skin aging through skin measurements faces limitations, making perceived age evaluation a more valuable and direct tool for assessing skin aging. Given that the aging process markedly affects the appearance of the eye contour, characterizing the eye region could be beneficial for perceived age assessment. This study aimed to analyze age-correlated changes in the eye contour within the Chinese Han female population and to develop, validate, and apply a multiple linear regression model for predicting perceived age. MATERIALS AND METHODS: A naïve panel of 107 Chinese women assessed the perceived ages of 212 Chinese Han women. Instrumental analysis evaluated periorbital parameters, including palpebral fissure width (PFW), palpebral fissure height (PFH), acclivity of palpebral fissure (AX), angle of inner canthal (AEN), and angle of outer canthal (AEX). These parameters were used to construct a multiple linear regression model for predicting the perceived ages of Chinese Han women. A combined treatment using Fotona 4D and an anti-aging eye cream, formulated with plant extracts, peptides, and antioxidants, was conducted to verify the cream's anti-aging efficacy and safety. This eye cream was then tested in a large-scale clinical trial involving 101 participants. The prediction model was employed in this trial to assess the perceived ages of the women after an 8-week application of the eye cream. RESULTS: All parameters were observed to decrease with age. An intergroup comparison indicated that eyelid aging in Chinese Han women accelerates beyond the age of 50. Consequently, a linear regression model was constructed and validated, with the perceived age being calculated as 183.159 - 1.078 * AEN - 4.487 * PFW + 6.061 * PFH - 1.003 * AX - 0.328 * AEX. The anti-aging efficacy and safety of the eye cream were confirmed through combined treatment with Fotona 4D, showing improvements in wrinkles, elasticity, and dark circles under the eyes. In a large-scale clinical evaluation using this eye cream, a perceived age prediction model was applied, suggesting that 8 weeks of use made participants appear 2.25 years younger. CONCLUSION: Our study developed and validated a multiple linear regression model to predict the perceived age of Chinese Han women. This model was successfully utilized in a large-scale clinical evaluation of anti-aging eye cream, revealing that 8 weeks of usage made participants appear 2.25 years younger. This method effectively bridges the gap between clinical research and consumer perceptions, explores the complex factors influencing perceived age, and aims to improve anti-aging formulations.

Speculum-free portable preterm imaging system.

Significance: Preterm birth is defined as a birth before 37 weeks of gestation and is one of the leading contributors to infant mortality rates globally. Premature birth can lead to life-long developmental impairment for the child. Unfortunately, there is a significant lack of tools to diagnose preterm birth risk, which limits patient care and the development of new therapies. Aim: To develop a speculum-free, portable preterm imaging system (PPRIM) for cervical imaging; testing of the PPRIM system to resolve polarization properties of birefringent samples; and testing of the PPRIM under an IRB on healthy, non-pregnant volunteers for visualization and polarization analysis of cervical images. Approach: The PPRIM can perform 4×3 Mueller-matrix imaging to characterize the remodeling of the uterine cervix during pregnancy. The PPRIM is built with a polarized imaging probe and a flexible insertable sheath made with a compatible flexible rubber-like material to maximize comfort and ease of use. Results: The PPRIM device is developed to meet specific design specifications as a speculum-free, portable, and comfortable imaging system with polarized imaging capabilities. This system comprises a main imaging component and a flexible silicone inserter. The inserter is designed to maximize comfort and usability for the patient. The PPRIM shows high-resolution imaging capabilities at the 20 mm working distance and 25 mm circular field of view. The PPRIM demonstrates the ability to resolve birefringent sample orientation and full field capture of a healthy, non-pregnant cervix. Conclusion: The development of the PPRIM aims to improve access to the standard of care for women's reproductive health using polarized Mueller-matrix imaging of the cervix and reduce infant and maternal mortality rates and better quality of life.

Combination of dimethylmethoxy chromanol and turmeric root extract synergically attenuates ultraviolet-induced oxidative damage by increasing endogenous antioxidants in HaCaT cells.

BACKGROUND: Repeated exposure to UV generates excessive reactive oxygen species (ROS) and damages the enzymatic antioxidant defense system including quinone oxidoreductase 1 (NQO1) and superoxide dismutase (SOD) in skin. Topical application of antioxidants may prevent the undesired damage of cellular proteins, lipids and DNA in skin. Dimethylmethoxy chromanol (DMC) is a bioinspired molecule, designed to be a structural analog to the γ-tocopherol that is naturally present in vegetables and plants. Turmeric root extract (TRE) is from a plant in South Asia extensively used as a food spice & vegetable, and its main components are turmerones. As both DMC and TRE are strong antioxidants with complementary antioxidation mechanisms, the aim of this study was to investigate the enhanced protective effects of their combination on oxidative damage in HaCaT cells following UVB exposure. MATERIALS AND METHODS: The effects of single and combined administrations of DMC and TRE on the SOD activity of HaCaT cells were evaluated by the SOD assay and qPCR. The NQO1 expression in the UVB-treated HaCaT cells was analyzed by the Western Blot. Furthermore, a clinical test involving 24 subjects was conducted to evaluate the in vivo antioxidation efficacies of the serum formulated with the combination of DMC and TRE at the optimal weight ratio. RESULTS: SOD assay showed that pretreating DMC or TRE alone could not preserve the impaired HaCaT SOD activity after UVB treatment. DMC and TRE at 1:1 weight ratio was the optimal combination to enhance the HaCaT SOD activity by approximately more than 1-fold compared with either of the single treated groups. No enhancement effect was observed at other mixing ratios. The 1:1 weight ratio was further proved to be optimal as this combination boosted the NQO1 expression by more than 50%, whereas no boosting effect was observed at other mixing ratios. The clinical test of the serum containing this optimal antioxidant combination demonstrated promising in vivo antioxidation efficacies after 4-week use, including 7.16% improvement in skin lightening, 18.29% reduction in skin redness, 35.68% decrease in TEWL, 19.05% increase in skin gloss and 32.04% enhancement in skin firmness. CONCLUSION: Collectively, our results indicated that the combination of DMC and TRE at 1:1 weight ratio attenuated the UV-induced oxidative damage by synergistically boosting endogenous antioxidant enzyme activity in HaCaT cells. Therefore, this optimal antioxidant combination is a promising treatment to boost skin antioxidation defense system.

Artificial intelligence-aided detection for prostate cancer with multimodal routine health check-up data: an Asian multi-center study.

BACKGROUND: The early detection of high-grade prostate cancer (HGPCa) is of great importance. However, the current detection strategies result in a high rate of negative biopsies and high medical costs. In this study, the authors aimed to establish an Asian Prostate Cancer Artificial intelligence (APCA) score with no extra cost other than routine health check-ups to predict the risk of HGPCa. PATIENTS AND METHODS: A total of 7476 patients with routine health check-up data who underwent prostate biopsies from January 2008 to December 2021 in eight referral centres in Asia were screened. After data pre-processing and cleaning, 5037 patients and 117 features were analyzed. Seven AI-based algorithms were tested for feature selection and seven AI-based algorithms were tested for classification, with the best combination applied for model construction. The APAC score was established in the CH cohort and validated in a multi-centre cohort and in each validation cohort to evaluate its generalizability in different Asian regions. The performance of the models was evaluated using area under the receiver operating characteristic curve (ROC), calibration plot, and decision curve analyses. RESULTS: Eighteen features were involved in the APCA score predicting HGPCa, with some of these markers not previously used in prostate cancer diagnosis. The area under the curve (AUC) was 0.76 (95% CI:0.74-0.78) in the multi-centre validation cohort and the increment of AUC (APCA vs. PSA) was 0.16 (95% CI:0.13-0.20). The calibration plots yielded a high degree of coherence and the decision curve analysis yielded a higher net clinical benefit. Applying the APCA score could reduce unnecessary biopsies by 20.2% and 38.4%, at the risk of missing 5.0% and 10.0% of HGPCa cases in the multi-centre validation cohort, respectively. CONCLUSIONS: The APCA score based on routine health check-ups could reduce unnecessary prostate biopsies without additional examinations in Asian populations. Further prospective population-based studies are warranted to confirm these results.

Design and synthesis of 9-phenanthranilamide derivatives and the study of anti-inflammatory, antioxidant and neuroprotective activities.

Oxidative stress and a series of excessive inflammatory responses are major obstacles to neurological functional recovery after ischemic stroke. In this study, we synthesized several novel 9-phenanthranilamide derivatives and evaluated their anti-inflammatory and antioxidant activities. Among the initially screened compounds, most could strongly inhibi lipopolysaccharide (LPS)-stimulated production of IL-1ß, IL-6 and TNF-α in microglial cells. Additionally, compounds 8b, 8q, 8r and 8s significantly inhibited the production of NO, and they also had dose-dependent protective effects on PC12 neuronal cells induced by H2O2. The antineuroinflammatory effects of 8r and 8s were associated with the downregulation of LPS-induced inflammatory mediators of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and both compounds inhibited the NF-κB signaling pathway. Further examinations showed that 8s had a significant neuroprotective effect on rats with middle cerebral artery occlusion (MCAO). It decreased the infarct volume and the neurological deficit score. Overall, our results suggested that compound 8s might be a promising agent for stroke treatment.

Components of the JNK-MAPK pathway play distinct roles in hepatocellular carcinoma.

PURPOSE: Mitogen-activated protein kinases (MAPK), specifically the c-Jun N-terminal kinase (JNK)-MAPK subfamily, play a crucial role in the development of various cancers, including hepatocellular carcinoma (HCC). However, the specific roles of JNK1/2 and their upstream regulators, MKK4/7, in HCC carcinogenesis remain unclear. METHODS: In this study, we performed differential expression analysis of JNK-MAPK components at both the transcriptome and protein levels using TCGA and HPA databases. We utilized Kaplan-Meier survival plots and receiver operating characteristic (ROC) curve analysis to evaluate the prognostic performance of a risk scoring model based on these components in the TCGA-HCC cohort. Additionally, we conducted immunoblotting, apoptosis analysis with FACS and soft agar assays to investigate the response of JNK-MAPK pathway components to various death stimuli (TRAIL, TNF-α, anisomycin, and etoposide) in HCC cell lines. RESULTS: JNK1/2 and MKK7 levels were significantly upregulated in HCC samples compared to paracarcinoma tissues, whereas MKK4 was downregulated. ROC analyses suggested that JNK2 and MKK7 may serve as suitable diagnostic genes for HCC, and high JNK2 expression correlated with significantly poorer overall survival. Knockdown of JNK1 enhanced TRAIL-induced apoptosis in hepatoma cells, while JNK2 knockdown reduced TNF-α/cycloheximide (CHX)-and anisomycin-induced apoptosis. Neither JNK1 nor JNK2 knockdown affected etoposide-induced apoptosis. Furthermore, MKK7 knockdown augmented TNF-α/CHX- and TRAIL-induced apoptosis and inhibited colony formation in hepatoma cells. CONCLUSION: Targeting MKK7, rather than JNK1/2 or MKK4, may be a promising therapeutic strategy to inhibit the JNK-MAPK pathway in HCC therapy.

Discovery of Coixol Derivatives as Potent Anti-inflammatory Agents.

Coixol, a derivative of 2-benzoxazolinone extracted from coix (Coix lachryma-jobi L. var. ma-yuen Stapf), has demonstrated promising anti-inflammatory activity and low cytotoxicity. In this study, 26 coixol derivatives were designed and synthesized by hybridization with cinnamic acid to identify new anti-inflammatory agents. The anti-inflammatory activities of the derivatives were screened using LPS-induced overexpression of nitric oxide (NO) in RAW264.7 macrophages. On the basis of the screening results, compounds containing furan (9c) or nitrofuran (9j) moieties displayed more pronounced activity than coixol and celecoxib. Mechanistic investigations revealed that 9c and 9j suppressed the expression of induced nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß, which was associated with the inhibition of the nuclear factor (NF)-κB signaling pathway. In vivo studies confirmed the anti-inflammatory activity of 9c and 9j in a xylene-induced mice auricles edema model. The preliminary in vitro and in vivo research findings suggest that 9c and 9j have the potential to be developed as anti-inflammatory agents.

LNP-miR-155 cy5 Inhibitor Regulates the Copper Transporter via the ß-Catenin/TCF4/SLC31A1 Signal for Colorectal Cancer Therapy.

Lipid nanoparticle (LNP) delivery systems are widely used in the delivery of small-molecule drugs and nucleic acids. In this study, we prepared LNP-miR-155 by lipid nanomaterial technology and investigated the effects of LNP-miR-155 on ß-catenin/transcription factor 4 (TCF4)/solute carrier family 31 member 1/copper transporter 1 (SLC31A1/CTR1) signaling and copper transport in colorectal cancer. For this, we used an LNP-miR-155 cy5 inhibitor and LNP-miR-155 cy5 mimics for the transfection of HT-29/SW480 cells. The transfection efficiency and uptake efficiency were detected by immunofluorescence. Relevant cell assays confirmed that the LNP-miR-155 cy5 inhibitor mediates the regulation of copper transport through the ß-catenin/TCF4/SLC31A1 axis. The LNP-miR-155 cy5 inhibitor reduced cell proliferation, migration, and colony formation and promoted cell apoptosis. We also confirmed that miR-155 downregulates HMG box-containing protein 1 (HBP1) and adenomatous polyposis coli (APC) in cells and activates the function of ß-catenin/TCF4 signaling. In addition, we found that the copper transporter, SLC31A1, is highly expressed in colorectal cancer cells. Furthermore, we also found that the complex ß-catenin/TCF4 promotes the transcription of SLC31A1 by binding to its promoter region, which sustains the transport of copper from the extracellular region to the intracellular region and increases the activities of Cu2+-ATPase and superoxide dismutase (SOD). In summary, the LNP-miR-155 cy5 inhibitor regulates ß-catenin/TCF4 by downregulating SLC31A1-mediated copper transport and intracellular copper homeostasis.

Orf virus DNA prime-protein boost strategy is superior to adenovirus-based vaccination in mice and sheep.

Contagious ecthyma (Orf), an acute and highly contagious zoonosis, is prevalent worldwide. Orf is caused by Orf virus (ORFV), which mainly infects sheep/goats and humans. Therefore, effective and safe vaccination strategies for Orf prevention are needed. Although immunization with single-type Orf vaccines has been tested, heterologous prime-boost strategies still need to be studied. In the present study, ORFV B2L and F1L were selected as immunogens, based on which DNA, subunit and adenovirus vaccine candidates were generated. Of note, heterologous immunization strategies using DNA prime-protein boost and DNA prime-adenovirus boost in mice were performed, with single-type vaccines as controls. We have found that the DNA prime-protein boost strategy induces stronger humoral and cellular immune responses than DNA prime-adenovirus boost strategy in mice, which was confirmed by the changes in specific antibodies, lymphocyte proliferation and cytokine expression. Importantly, this observation was also confirmed when these heterologous immunization strategies were performed in sheep. In summary, by comparing the two immune strategies, we found that DNA prime-protein boost strategy can induce a better immune response, which provides a new attempt for exploring Orf immunization strategy.

The synergistic effect of retinyl propionate and hydroxypinacolone retinoate on skin aging.

BACKGROUND: Aging is responsible for the majority of skin and soft tissue remolding in humans. Retinol and its derivatives or retinoids effectively intervene skin aging process. Nevertheless, retinoids usually induce skin intolerance, especially among the Chinese, and thus, their application to prevent skin aging is yet to be well accepted. The study of optimal composition and concentration of retinoids is necessary to offer strong antiaging efficacies with minimum irritations. Therefore, a better understanding of retinol and its derivatives is acutely needed to develop strategies to combat skin aging. OBJECTIVE: In this study, we aimed to determine the optimal ratio of two retinol derivatives-hydroxypinacolone retinoate (HPR) and retinyl propionate (RP) in terms of dermal remodeling and skin aging prevention-and to investigate their synergistic antiaging effects both in vitro and in vivo. METHODS: An in vitro human foreskin fibroblast (HFF-1) cell model was established to evaluate the cell viability of HPR and/or RP treatment. In addition, the antiaging and retinol receptor genes expressions in HFF-1 cells cotreated with HPR and RP were quantified. The in vivo adverse reaction evaluation of skincare serums containing various levels of retinol or the optimal HPR and RP combination termed Gravi-A was performed by 24 h patch tests in 33 subjects prior to the clinical research. Last but not the least, clinical research with 42 Chinese urban women was conducted to assess the in vivo antiaging efficacy of the skincare serum containing this optimal retinoid combination. RESULTS: The combination of HPR and RP at the weight ratio of 5:9 was shown to achieve the optimal in vitro antiaging performance. Coadministration of 5 µg/mL HPR and 9 µg/mL RP to HFF-1 cells promoted their proliferation at 24 h and synergistically enhanced the expressions of type IV collagen, CRBP-I, and RARB genes. In addition, the skincare serum containing HPR and RP combination at 5:9 weight ratio demonstrated superior in vivo anti-wrinkle and skin elasticity improvement benefits without any adverse reactions, while retinol in the same concentration exerted much higher adverse effect. Skin wrinkles, skin smoothness, TEWL, skin elasticity R2 and R5 were improved by 8.3%, 11.9%, 25.7%, 14.5%, and 22.6%, respectively, after 8-week use. CONCLUSION: Our results indicated the advanced antiaging effect of HPR and RP combination both in vitro and in vivo. In addition, little adverse effect was observed in this study, in comparison with retinol. This combination named as Gravi-A is a potential therapeutic strategy to prevent skin aging, especially for Chinese women.

Oncolytic Parapoxvirus induces Gasdermin E-mediated pyroptosis and activates antitumor immunity.

The advantage of oncolytic viruses (OV) in cancer therapy is their dual effect of directly killing tumours while prompting anti-tumour immune response. Oncolytic parapoxvirus ovis (ORFV) and other OVs are thought to induce apoptosis, but apoptosis, being the immunogenically inert compared to other types of cell death, does not explain the highly inflamed microenvironment in OV-challenged tumors. Here we show that ORFV and its recombinant therapeutic derivatives are able to trigger tumor cell pyroptosis via Gasdermin E (GSDME). This effect is especially prominent in GSDME-low tumor cells, in which ORFV-challenge pre-stabilizes GSDME by decreasing its ubiquitination and subsequently initiates pyroptosis. Consistently, GSDME depletion reduces the proportion of intratumoral cytotoxic T lymphocytes, pyroptotic cell death and the success of tumor ORFV virotherapy. In vivo, the OV preferentially accumulates in the tumour upon systemic delivery and elicits pyroptotic tumor killing. Consequentially, ORFV sensitizes immunologically 'cold' tumors to checkpoint blockade. This study thus highlights the critical role of GSDME-mediated pyroptosis in oncolytic ORFV-based antitumor immunity and identifies combinatorial cancer therapy strategies.

Redefining Mandibular Sub-units: The "ABC" Classification and Surgical Strategies for Lower Face Contouring.

BACKGROUND: In east Asia, lower face contouring surgeries including reduction mandibuloplasty and genioplasty are the most popular aesthetic craniofacial surgeries. Conventional selection of surgical strategies mainly relied on the visual judgment of the mandibular angle, without overall assessment of the mandibular sub-units. Furthermore, only a few studies offered quantitative assessment of the mandibular shape. METHODS: From 2010 to 2021, 1241 patients diagnosed with square faces and received customized lower face contouring surgeries by the senior author were reviewed and analyzed to propose an "ABC" classification system for facilitating surgical planning. RESULTS: Among them, 998 (80.42%) received bilateral mandible reshaping, 155 (12.49%) underwent bilateral mandible reshaping combined with genioplasty, and 88 (7.09%) received asymmetric mandible reshaping. A modified classification system composed of three critical parameters (height, morphology/thickness, divergence) in three aesthetic zones (mandibular angle, mandibular body, chin) was proposed based on quantitative summarization of the CT database and the senior author's 12-year experience. The way to facilitate surgical planning with this classification was demonstrated. CONCLUSIONS: This modified classification system ushered a decision-making process that prioritized several critical measurements and proposed an operative planning form. Meanwhile, it can also be cooperated into the three-dimensional virtual surgical plan. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

Clinical Research into Treating Unexplained Recurrent Spontaneous Abortion during Early Pregnancy with the Qing Yi Tiao Mian Formula.

OBJECTIVE: The present study aims to analyze the clinical effect of the Qing Yi Tiao Mian (QYTM) formula on unexplained recurrent spontaneous abortion (URSA) during early pregnancy and the immune balance of T lymphocytes. METHODS: With their consent, 45 patients with URSA in weeks 4-9 of pregnancy were separated into three groups, i.e., the conventional fetal protection (n = 15), prednisone treatment (n = 10), and QYTM formula treatment (n = 20) groups. These patients received treatment once they had been diagnosed with an intrauterine pregnancy. The conventional fetal protection group was given progesterone (20 ∼ 40 mg daily injection) for four weeks. The prednisone treatment group was given progesterone (20 ∼ 40 mg daily injection) + prednisone (5 mg/d) for four weeks. The QYTM formula treatment group was given progesterone (20 ∼ 40 mg daily injection) + QYTM formula (one dose per day) for four weeks. In addition, women who had previously had a normal pregnancy were enrolled as a control group (n = 18). The success rate of the pregnancy in the first trimester was observed in each group, and the proportion of T lymphocytes in the peripheral blood before and after treatment was recorded. RESULTS: Among the 20 patients with URSA in the QYTM formula treatment group, 19 remained pregnant. Thus, the success rate during early pregnancy was 95%, which was significantly higher than the conventional fetal protection (53.33%) and prednisone treatment (70%) groups. The CD8+ T and natural killer (NK) cells population in the URSA groups was higher compared with the control group (P < 0.01). The QYTM formula treatment significantly decreased the ratio of CD8+ T lymphocytes (P < 0.01) and NK cells (P < 0.01). CONCLUSION: The QYTM formula significantly decreased the spontaneous abortion rate in patients with URSA during early pregnancy. The mechanism may be closely related to the inhibition of the killer lymphocytes' proliferation by CD8+ T lymphocytes and NK cells.

Soft and Hard Tissue Changes and Facial Rejuvenation of Anterior Maxillary Segmental Osteotomy: A Three-Dimensional Cephalometric Study.

OBJECTIVE: To explore the efficacy of anterior maxillary segmental osteotomy (AMSO) in reliving maxillary protrusion and better analyze the three-dimensional (3D) morphological changes of the postoperative nasolabial region using computed tomography (CT) and evaluate the trend of facial rejuvenation. MATERIALS AND METHODS: Forty-five patients who underwent AMSO from January 2017 to December 2021 were retrospectively included. CT and oriented photography were performed before and 10 months after the treatment. The mimics17.0 software was used to reconstruct the 3D CT scan results before and after the operation, measure the data of each anatomical index, and systematically evaluate the soft tissue changes in the nasolabial region. The patients themselves, the plastic surgeons, family members, or friends of patients use the Face-Q Age Appraisal Visual Analogue Scale (VAS) to evaluate the changes in patients' visual age before and after the operation. RESULTS: Forty-five cases of maxillary protrusion were alleviated. Seen from the side, the protruding degree of the upper lip is obviously reduced. In the front view, âˆ Cont-Sbal-F, the width of alar base, and alae nasi all increased significantly. Contrary to traditional perceptions, the protrusion and height of the nose tip actually increased rather than decreased after AMSO. The visual age score improved positively, and patients obtained facial rejuvenation. No serious complications occurred; after 10-month follow-up, we achieved a high degree of satisfaction. CONCLUSION: AMSO can significantly improve the maxillary protrusion, and it can increase the protrusion and height of the nose tip. Also, patients can get a younger appearance. Comprehensive preoperative evaluation and postoperative nasolabial morphology with maxillary protrusion patients are helpful for correct clinical decision-making. At the same time, the operation suggests a new choice of facial rejuvenation for patients with maxillary protrusion. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266.

Parapoxvirus-based therapy eliminates SARS-CoV-2-loaded fine aerosol and blocks viral transmission in hamster models.

Currently, it is believed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an airborne virus, and virus-containing aerosol particles have been found concurrent with the onset of COVID-19, which may contribute to the noncontact transmission of SARS-CoV-2. Exploring agents to block SARS-CoV-2 transmission is of great importance to prevent the COVID-19 pandemic. In this study, we found that inactivated Parapoxvirus ovis (iORFV), a kind of immunomodulator, could compress the proportion of small particle aerosols exhaled by Syrian golden hamsters. Notably, the concentration of SARS-CoV-2 RNA-containing aerosol particles was significantly reduced by iORFV in the early stages after viral inoculation. Importantly, smaller aerosol particles (<4.7 µm) that carry infectious viruses were completely cleared by iORFV. Consistently, iORFV treatment completely blocked viral noncontact (aerosol) transmission. In summary, iORFV may become a repurposed agent for the prevention and control of COVID-19 by affecting viral aerosol exhalation and subsequent viral transmission.

Dynamic Batch Process Monitoring Based on Time-Slice Latent Variable Correlation Analysis.

Batch processes are generally characterized by complex dynamics and remarkable data collinearity, thereby rendering the monitoring of such processes necessary but challenging. This paper proposes a data-driven time-slice latent variable correlation analysis-based model predictive fault detection framework to ensure accurate fault detection in dynamic batch processes. The three-way batch process data are first unfolded into the two-way time slice. For each single time slice, process data are mapped to both major latent variables and residual subspaces to deal with the variable-wise data collinearity and extract dominant data information. A measurement status is then determined with a canonical correlation analysis of the major latent variables and correlated variables, using both the time and batch perspectives. Prediction-based residuals are generated, which provide the basis for identifying the property of faults detected, namely, static or dynamic. Based on experiments using a simulated penicillin production and an industrial inject molding process, the proposed monitoring scheme has been proven feasible and effective.

Evaluation of the Immune Response Afforded by Combined Immunization with Orf Virus DNA and Subunit Vaccine in Mice.

Contagious ecthyma (Orf) is a highly contagious disease caused by Orf virus (ORFV) infection. Orf is prevalent all over the world and, not only affects the healthy development of sheep husbandry, but also threatens human health. However, there are no safe and effective vaccines or drugs for the prevention and treatment of Orf at present. In this study, we constructed a DNA plasmid expressing ORFV B2L and F1L genes as a DNA vaccine candidate, with purified B2L full-length protein and F1L truncated protein as subunit vaccine candidates. BALB/c mice were immunized with the DNA vaccine, subunit vaccine, as well as DNA prime-protein boost strategies. The results showed that compared with the DNA vaccine and subunit vaccine alone, the DNA prime-protein boost immunization group had a higher level of specific antibodies, stronger lymphocyte proliferation, and higher expression of cytokines such as IL-2, IL-4, IL-6, IFN-γ, and TNF-α, which are considered to cause a Th1/Th2 mixed cytokine response. Our results demonstrated that the DNA prime-protein boost immunization strategy induced stronger humoral and cellular immune responses, which have potential advantages in preventing ORFV infection.

Design and synthesis of novel indole and indazole-piperazine pyrimidine derivatives with anti-inflammatory and neuroprotective activities for ischemic stroke treatment.

Microglia-mediated neuroinflammation plays an important role in ischemic stroke (IS). In this work, a series of novel indole and indazole-piperazine pyrimidine derivatives with anti-neuroinflammatory and neuroprotective activities were designed and synthesized for treatment of IS. Among these compounds, 5j displayed the most attractive cytoprotective effect against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced damage in BV2 cells. Meanwhile, it significantly ameliorated the release of inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, nitric oxide (NO) and prostaglandin E2 (PGE2), from lipopolysaccharide (LPS)-induced BV2 cells. Moreover, 5j can decrease the release of TNF-α and IL-1ß form LPS-induced mouse brain neuroinflammation model. As a potent inhibitor against both cyclooxygenase-2 (COX-2, IC50 = 92.54 nM) and 5-lipoxygenase (5-LOX, IC50 = 41.86 nM), 5j inhibited the M1 phenotype polarization of microglia and promoted the M2 phenotype polarization of microglia. Additionally, 5j exhibited remarkable neuroprotection in middle cerebral artery occlusion (MCAO) rats by reducing their infarct volumes and neurological deficit scores. In conclusion, 5j has the potential for the treatment of stroke as an anti-inflammatory and neuroprotective agent.