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Purpose: The aim of this study is to investigate the role of the neutrophil to lymphocyte ratio (NLR) in patients diagnosed with the chronic obstructive pulmonary disease-obstructive sleep apnea (COPD-OSA) overlap syndrome and comorbid pulmonary hypertension (PH). Patients and methods: We enrolled a consecutive of stable COPD patients and conducted spirometry measurements, nocturnal polysomnography (PSG), and echocardiography for all participants. Clinical laboratory data were collected. Results: A total of 178 patients with stable COPD were enrolled among whom 33.14% (59/178) were diagnosed with OSA. Of the patients with overlap syndrome, 35.59% (21/59) showed comorbid PH, compared to 34.45% (41/119) in COPD patients without OSA. There was no significant difference in the occurrence of PH between COPD with and without OSA. NLR was significantly higher in patients with overlap syndrome compared to those with either disease alone. The difference in NLR between COPD-OSA patients with and without PH was not significant. Correlation analysis revealed that NLR was associated with age, total sleep time spent with oxygen saturation below 90% (T90), CRP, pulmonary artery systolic pressure (PASP), and minimum peripheral capillary oxygen saturation (SpO2min) in all COPD patients. NLR was identified as an independent factor contributing to OSA in COPD. The median cut-off value for detecting OSA in stable COPD was 2.49. However, NLR was not found to be a predictor for PH in COPD-OSA overlap syndrome. Conclusions: NLR can serve as a predictive marker for comorbid OSA in patients with COPD. NLR is expected to increase its clinical application as a convenient and cost-effective biomarker for COPD-OSA overlap syndrome. [ABSTRACT FROM AUTHOR]

2,6-Di-tert-butyl-4-methylphenol (BHT) is an excellent antioxidant that is easily oxidized to 2,6-di-tert-butyl-4-hydroperoxyl-4-methyl-2,5-cyclohexadienone (BHTOOH). For the safety of BHT production and usage, it is meaningful to study the thermal stability and decomposition properties of BHT and BHTOOH. In this paper, the thermal decomposition properties of BHT and BHTOOH were compared by the mini closed pressure vessel test (MCPVT) and differential scanning calorimetry (DSC). Their kinetics of thermal decomposition were studied using thermogravimetric analysis (TGA). The thermal decomposition products of BHT and BHTOOH were analyzed by gas chromatography-mass spectrometry (GC–MS). The results show that there was no significant change in temperature pressure when BHT was warmed up under a nitrogen atmosphere, indicating that BHT was stable within 400 K. The thermal decomposition reaction of BHTOOH was rapid with an initial reaction temperature of 375.2 K. The initial exothermic temperature (Ti) and heat release (QDSC) of DSC were 384.9 K and 865.0 J g−1, respectively. The apparent activation energies (Ea) for the thermal decomposition reactions of BHT and BHTOOH calculated by the Kissinger method were 151.8 kJ mol−1 and 66.07 kJ mol−1, respectively. The main decomposition products of BHT were isobutene and 2-tert-butyl-4-methylphenol. The thermal decomposition products of BHTOOH included BHT, 2,6-di-tert-butyl-4-ethylphenol, 3,5-di-tert-butyl-4-hydroxybenzaldehyde, 4,4′-(1,2-ethanediyl) bis [2,6-bis (1,1-dimethylethyl) phenol, etc. Based on the thermal decomposition behavior and products, the reaction pathway has been described. These results indicate that BHT is a potential thermal hazard during production, storage and application. For the safety of the chemical industry, the oxidation of BHT should be avoided. [ABSTRACT FROM AUTHOR]

Propionic acidaemia is a rare disorder caused by defects in the propionyl-coenzyme A carboxylase α or β (PCCA or PCCB) subunits that leads to an accumulation of toxic metabolites and to recurrent, life-threatening metabolic decompensation events. Here we report interim analyses of a first-in-human, phase 1/2, open-label, dose-optimization study and an extension study evaluating the safety and efficacy of mRNA-3927, a dual mRNA therapy encoding PCCA and PCCB. As of 31 May 2023, 16 participants were enrolled across 5 dose cohorts. Twelve of the 16 participants completed the dose-optimization study and enrolled in the extension study. A total of 346 intravenous doses of mRNA-3927 were administered over a total of 15.69 person-years of treatment. No dose-limiting toxicities occurred. Treatment-emergent adverse events were reported in 15 out of the 16 (93.8%) participants. Preliminary analysis suggests an increase in the exposure to mRNA-3927 with dose escalation, and a 70% reduction in the risk of metabolic decompensation events among 8 participants who reported them in the 12-month pretreatment period.Interim data from a clinical trial of mRNA-3927—an mRNA therapeutic for propionic acidaemia—provide early indications of the safety and efficacy of the treatment, and suggest that this approach might be applicable to other rare diseases. [ABSTRACT FROM AUTHOR]

This paper verifies the low Mach number limit of the non-isentropic compressible magnetohydrodynamic (MHD) equations with or without the magnetic diffusion in a three-dimensional bounded domain when the temperature variation is large but finite. The uniform estimates of strong solutions are established in a short time interval independent of the Mach number, provided that the slip boundary condition for the velocity and the Neumann boundary condition for the temperature are imposed and the initial data is well-prepared. [ABSTRACT FROM AUTHOR]

Introduction: Brain metastasis (BM) is an aggressive complication with an extremely poor prognosis in patients with small-cell lung cancer (SCLC). A well-constructed prognostic model could help in providing timely survival consultation or optimizing treatments. Methods: We analyzed clinical data from SCLC patients between 2000 and 2018 based on the Surveillance, Epidemiology, and End Results (SEER) database. We identified significant prognostic factors and integrated them using a multivariable Cox regression approach. Internal validation of the model was performed through a bootstrap resampling procedure. Model performance was evaluated based on the area under the curve (AUC) and calibration curve. Results: A total of 2,454 SCLC patients' clinical data was collected from the database. It was determined that seven clinical parameters were associated with prognosis in SCLC patients with BM. A satisfactory level of discrimination was achieved by the predictive model, with 6-, 12-, and 18-month AUC values of 0.726, 0.707, and 0.737 in the training cohort; and 0.759, 0.742, and 0.744 in the validation cohort. As measured by survival rate probabilities, the calibration curve agreed well with actual observations. Furthermore, prognostic scores were found to significantly alter the survival curves of different risk groups. We then deployed the prognostic model onto a website server so that users can access it easily. Conclusions: In this study, a nomogram and a web-based predictor were developed to predict overall survival in SCLC patients with BM. It may assist physicians in making informed clinical decisions and determining the best treatment plan for each patient. [ABSTRACT FROM AUTHOR]

Obesity is characterized by chronic low-grade inflammation, which is driven by macrophage infiltration in adipose tissue and leads to elevated cytokines such as interleukin-1β (IL-1β) in the circulation and tissues. Previous studies demonstrate that SENP3, a redox-sensitive SUMO2/3-specific protease, is strongly implicated in the development and progression of cancer and cardiovascular diseases. However, the role of SENP3 in obesity-associated inflammation remains largely unknown. To better understand the effects of SENP3 on adipose tissue macrophage (ATM) activation and function within the context of obesity, we generated mice with myeloid-specific deletion of SENP3 (Senp3flox/flox;Lyz2-Cre mice). We found that the expression of SENP3 is dramatically increased in ATMs during high-fat diet (HFD)-induced obesity in mice. Senp3flox/flox;Lyz2-Cre mice show lower body weight gain and reduced adiposity and adipocyte size after challenged with HFD and during aging. Myeloid-specific SENP3 deletion attenuates macrophage infiltration in adipose tissue and reduces serum levels of inflammatory factors during diet and age-induced obesity. Furthermore, we found that SENP3 knockout markedly inhibits cytokine release from macrophage after lipopolysaccharide and palmitic acid treatment in vitro. Mechanistically, in cultured peritoneal macrophages, SENP3 protein level is enhanced by IL-1β, in parallel with the upregulation of Yes-associated protein 1 (YAP1). Moreover, we demonstrated that SENP3 modulates de-SUMO modification of YAP1 and SENP3 deletion abolishes the upregulation of YAP1 induced by IL-1β. Most importantly, SENP3 deficiency reduces YAP1 protein level in adipose tissue during obesity. Our results highlight the important role of SENP3 in ATM inflammation and diet and age-induced obesity. [ABSTRACT FROM AUTHOR]

Replication-competent oncolytic adenovirus (TOA2) gene therapy is a recently introduced anti-tumor treatment regimen with superior results. The biodistribution studies of virus vector-based medicine seem more cautious and have been given much attention recently in terms of its quality and safety in preclinical trials. The current study determined the biodistribution and safety of a replication-competent adenovirus in different organs to predict its toxicity threshold. The present study has used TOA2, while biodistribution analysis was performed in human lung carcinoma A549-induced tumor-bearing nude mice model. Intratumoral injection was applied onto tumor-bearing mice with the adenovirus (3×1010 VP per mouse). Mice were sacrificed at the end of the experiment and the organs were dissected. Biodistribution analysis was done with complete hexon gene detection in each organ using quantitative real-time polymerase chain reaction (qRT-PCR). The biodistribution and concentration profiles showed that the TOA2 is well distributed in the entire tumor tissue. After dose 3 at day 11, the concentration of the virus has increased in the tumor tissue from 2240.54 (± 01.69) copies/100 ng genome to 13,120.28 (± 88.21) copies/100 ng genome on the 18th day, which eventually approached 336.45 (± 23.41) copies/100ng genome on the day 36. On the contrary, the concentration of the same decreased in the order of the liver, kidney, spleen, lung, and heart over time but no distributional traces in gonads. But the concentration found decreased dramatically in blood and other organs, while at the end of the experiment no detectable distribution was seen besides tumor tissue. The study confirms that adenovirus-based tumor therapy using conditionally replicating competent oncolytic TOA2 exhibited great efficiency with no toxicity at all. [ABSTRACT FROM AUTHOR]

Myocardial remodeling and dysfunction are commonly observed in type 2 diabetes mellitus (T2DM). Aerobic exercise can partly alleviate diabetes-induced myocardial dysfunction through its antioxidant actions. MOTS-c is a potential exercise mimic. This study aimed to investigate the effects of MOTS-c on improving diabetic heart function and its mechanism and to identify whether MOTS-c improved antioxidant defenses due to aerobic exercise. Herein, we established a rat model of T2DM induced by high-fat diet combined with a low-dose streptozotocin injection. Interventions were performed using intraperitoneal injections of MOTS-c (i.p. 0.5 mg/kg/day, 7 days/week) or aerobic exercise training (treadmill, 20 m/min, 60 min/day, 5 days/week) for 8 weeks. Myocardial ultrastructure was assessed using transmission electron microscopy (TEM), myocardial lipid peroxidation levels (MDA), superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) levels were assessed using colorimetric methods, and molecular analyses including MOTS-c, Kelch-like ECH-associated protein 1 (Keap1), Nuclear factor E2-related factor 2 (Nrf2), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)and phospho-AMPK (p-AMPK) were examined using Western blot. The results showed that MOTS-c, with or without exercise, reduced myocardial ultrastructural damage and improved glucolipid metabolism and cardiac function in T2DM. Furthermore, MOTS-c increased antioxidant markers such as SOD, CAT, and the protein expression of myocardial MOTS-c, Keap1, Nrf2, and p-AMPK. MOTS-c with exercise treatment reduced myocardial MDA and increased p-AMPK significantly comparing to only exercise or MOTS-c alone. Our findings suggest that MOTS-c may be a helpful supplement for overcoming exercise insufficiency and improving myocardial structure and function in diabetes. [ABSTRACT FROM AUTHOR]

Small-cell lung cancer (SCLC) is an aggressive lung cancer subtype with an extremely poor prognosis. The 5-year survival rate for limited-stage (LS)-SCLC cancer is 10–13%, while the rate for extensive-stage SCLC cancer is only 1–2%. Given the crucial role of the tumor stage in the disease course, a well-constructed prognostic model is warranted for patients with LS-SCLC. The LS-SCLC patients' clinical data extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2018 were reviewed. A multivariable Cox regression approach was utilized to identify and integrate significant prognostic factors. Bootstrap resampling was used to validate the model internally. The Area Under Curve (AUC) and calibration curve evaluated the model's performance. A total of 5463 LS-SCLC patients' clinical data was collected from the database. Eight clinical parameters were identified as significant prognostic factors for LS-SCLC patients' OS. The predictive model achieved satisfactory discrimination capacity, with 1-, 2-, and 3-year AUC values of 0.91, 0.88, and 0.87 in the training cohort; and 0.87, 0.87, and 0.85 in the validation cohort. The calibration curve showed a good agreement with actual observations in survival rate probability. Further, substantial differences between survival curves of the different risk groups stratified by prognostic scores were observed. The nomogram was then deployed into a website server for ease of access. This study developed a nomogram and a web-based predictor for predicting the overall survival of patients with LS-SCLC, which may help physicians make personalized clinical decisions and treatment strategies. [ABSTRACT FROM AUTHOR]

In this study, the oxidation characteristics of isoprene were investigated using a custom-designed mini closed pressure vessel test (MCPVT). The results show that isoprene is unstable and polymerization occurs under a nitrogen atmosphere. Under an oxygen atmosphere, the oxidation process of isoprene was divided into three stages: (1) isoprene reacts with oxygen to produce peroxide; (2) Peroxides produce free radicals through thermal decomposition; (3) Free radicals cause complex oxidation and thermal runaway reactions. The oxidation of isoprene conforms to the second-order reaction kinetics, and the activation energy was 86.88 kJ·mol−1. The thermal decomposition characteristics of the total oxidation product and purified peroxide mixture were determined by differential scanning calorimetry (DSC). The initial exothermic temperatures Ton were 371.17 K and 365.84 K, respectively. And the decomposition heat QDSC were 816.66 J·g−1 and 991.08 J·g−1, respectively. It indicates that high concentration of isoprene peroxide has a high risk of thermal runaway. The results of thermal runaway experiment showed that the temperature and pressure of isoprene oxidation were prone to rise rapidly, which indicates that the oxidation reaction was dangerous. The reaction products of isoprene were analyzed by gas chromatography-mass spectrometry (GC–MS). The main oxidation products were methyl vinyl ketone, methacrolein, 3-methylfuran, etc. The main thermal runaway products were dimethoxymethane, 2,3-pentanedione, naphthalene, etc. Based on the reaction products, the possible reaction pathway of isoprene was proposed. [ABSTRACT FROM AUTHOR]

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Endometrial damage repair disorder is the main reason of intrauterine adhesions (IUA) and thin endometrium (TA), which is caused by curettage or infection. Exosomal miRNAs derived from human umbilical cord mesenchymal stem cells (hucMSCs) were reported to play an important role in damage repair disorder, including endometrial fibrosis. In this study, we aimed to investigate the role of hucMSCs-derived exosomal microRNA-202-3p (miR-202-3p) in endometrial damage repair. We established rat endometrial injury model according to curettage to mimic women curettage abortion operation. The miRNA array analysis indicated that miR-202-3p was increased and matrix metallopeptidase 11 (MMP11) was decreased in the exosomes-treated rat uterine tissues. Bioinformatics analysis suggested that MMP11 is the target gene of miR-202-3p. We observed that the mRNA and protein of MMP11 were significantly decreased in exosome treatment group on day 3, and the components of extracellular matrix (ECM) COL1A1, COL3A1, COLVI and fibronectin (FN) protein were increased. And we found that when the injured human stromal cells were treated with miR-202-3p overexpression exosomes, the COLVI and FN were also upregulated in protein and mRNA expression level. For the first time MMP11 was proved to be the target gene of miR-202-3p by dual luciferase reporter system. At last, we found the state of stromal cells was better in miR-202-3p overexpression exosomes group compared to exosomes group, and miR-202-3p overexpression exosomes markedly upregulated the FN and collagen on day 3 after endometrial injury. We thought that miR-202-3p overexpression exosomes promoted endometrial repair by regulating ECM remodeling in early repair of damaged endometrium. Taken together, these experimental findings may provide a theoretical basis for understanding endometrial repair and an insight into the clinical treatment for IUA. [ABSTRACT FROM AUTHOR]

This article, published in the Chemistry of Natural Compounds journal, explores the use of the OSMAC strategy to enhance the diversity and yield of bioactive compounds from the endophytic fungus Xylaria sp. GDG-102. The fungus was cultivated in a rice medium with monosodium glutamate, resulting in the isolation of nine compounds with antibacterial properties against various bacteria. The article also presents crystal data for one of the compounds, (αR)-3-chloro-α,4-dihydroxybenzeneacetamide, for the first time. The text provides detailed information about the chemical properties of these compounds, including their molecular formulas, physical characteristics, and nuclear magnetic resonance (NMR) spectra. The research received support from the National Natural Science Foundation of China and the Guangxi Natural Science Foundation of China. [Extracted from the article]

Secondary metabolites from the genus I Metarhizium i yielded several bioactive compounds, such as metarhiziumoids A and B showed glycosidase inhibitory activity [[3]], omalvin A displayed antibacterial activity [[4]], and destruxin A exhibited phytotoxic activity [[5]]. I Metarhizium marquandii i is an endophytic fungus isolated from the Chinese medicinal plant I Sophora tonkinensis i (Leguminosae) I . i In our ongoing search for biologically active compounds from fungi [[6]-[9]], the metabolites of I M. marquandii i were investigated. At the concentration of 100 g/mL, compound B 2 b showed antifungal activity to all five fungi. Graph Compounds B 1-5 b were evaluated for their antifungal activities against five phytopathogenic fungi, I Alternaria alternaria i , I Alternaria cabbage i , I Cochliobolus miyabeanus i , I Colletotrichum capsici i , I Ceratocystis paradoxa i , using a modified version of the 2-fold serial dilutions method [[15]]. [Extracted from the article]

The education pathways and opportunities of schoolgirls in Asia are facing different challenges. The empirical studies have implemented Information and Communication Technology-enabled learning to expand such pathways and opportunities and promote education inclusiveness and equity. Through the Gender Analysis Framework, this review paper focuses on exploring and discussing how ICT-enabled learning may expand schoolgirls' education pathways and opportunities in Asia for inclusive and equitable education. This review covers 30 studies that adopted ICT-enabled learning, synthesizes, and presents four key ICT-enabled learning approaches: Emerging technologies-enabled learning, Digital game-based learning, Mobile-enabled learning, and Computer-assisted learning. Our result discusses about how different approaches in this review (in)directly impact on schoolgirls' access to assets, their practice and participation in learning activities, belief and perception of their own and other stakeholders', and how policies accommodate these approaches. The review further suggests several guidelines to develop an inclusive learning environment enabled by ICT to education pathways and opportunities of schoolgirls, thereby enhancing education inclusiveness and equity. [ABSTRACT FROM AUTHOR]

Vacuum brazing was used to join TC4 titanium alloy with self-designed and non-copper Ti–38Zr–24Ni (wt.%) filler metal. Variable brazing clearances were chosen to study their effect on the microstructural evolution and mechanical properties of the joints. The brazed joint with narrow brazing clearance only contained two reaction zones: the diffusion zone (α-Ti and (Ti, Zr)2Ni eutectoid structures and remained based metal) and the interface zone (α-Ti and (Ti,Zr)2Ni). However, the brazed joint with large brazing clearance had another reaction zone in the middle of the joint: the center zone (big block brittle (Ti,Zr)2Ni IMCs and some tiny phases: α-Ti and (Ti,Zr)2Ni eutectoid transformation phase). The width of center zone increased with the increase of the brazing clearance. The maximum shear strength of the brazed joint reached 872 MPa when brazing clearance was 0 μm. The brittleness of IMCs in center zone caused the low strength of the joint. Quasi-cleavage fracture occurred in the narrow brazing clearance (0 μm), while mixed quasi-cleavage and cleavage fractures occurred in the large brazing clearance (50-200 μm). [ABSTRACT FROM AUTHOR]

Introduction: Postoperative impaired sleep quality and pain are associated with adverse outcomes. Stellate ganglion block (SGB) has shown promising results in enhancing sleep quality and alleviating neuropathic pain. This study aimed to investigate the effects of ultrasound-guided SGB on postoperative sleep quality and pain in patients undergoing breast cancer surgery. Methods: This study is a parallel-group randomized controlled clinical trial with two groups: SGB and control. Fifty female patients undergoing breast cancer surgery were randomized in a 1:1 ratio to receive preoperative ultrasound-guided single-injection SGB (SGB group) or just an ultrasound scan (control group). All participants were blinded to the group assignment. The primary outcome was postoperative sleep quality, assessed by the St. Mary's Hospital Sleep Questionnaire and actigraphy 2 days postoperatively. The secondary outcome was postoperative pain, measured by the visual analog scale. Results: A total of 48 patients completed the study, with 23 patients in the control group and 25 in the SGB group. The postoperative St. Mary's Hospital Sleep Questionnaire scores were significantly higher in the SGB group than in the control group on 1 day postoperative (30.88 ± 2.44 versus 27.35 ± 4.12 points, P = 0.001). The SGB also increased the total sleep time and sleep efficiency (main actigraphy indicators) during the first two postoperative nights. Compared with the control group, preoperative SGB reduced postoperative pain and the incidence of breast cancer-related lymphedema (20% versus 52.2%, P = 0.02, odds ratio 0.229, 95% confidence interval 0.064–0.821). There were no adverse events related to SGB. Conclusion: Preoperative ultrasound-guided SGB improves postoperative sleep quality and analgesia in patients undergoing breast cancer surgery. SGB may be a safe and practical treatment to enhance the postoperative quality of life in patients with breast cancer. Trial Registration: The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100046620, principal investigator: Kai Zeng, date of registration: 23 May 2021). [ABSTRACT FROM AUTHOR]

We aimed to investigate the relationship of dietary zinc intake with new-onset hypertension among Chinese adults. A total of 12,177 participants who were free of hypertension at baseline from the China Health and Nutrition Survey were included. Dietary intake was assessed by three consecutive 24-h dietary recalls combined with a household food inventory. Participants with systolic blood pressure ≽ 140 mmHg or diastolic blood pressure ≽ 90 mmHg or diagnosed by a physician or under antihypertensive treatment during the follow-up were defined as having new-onset hypertension. During a median follow-up duration of 6.1 years, 4269 participants developed new-onset hypertension. Overall, the association between dietary zinc intake and new-onset hypertension followed a J-shape (P for non-linearity < 0.001). The risk of new-onset hypertension significantly decreased with the increment of dietary zinc intake (per mg/day: hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.88–0.98) in participants with zinc intake < 10.9 mg/day, and increased with the increment of zinc intake (per mg/day: HR 1.14; 95% CI 1.11–1.16) in participants with zinc intake ≽ 10.9 mg/day. In conclusion, there was a J-shaped association between dietary zinc intake and new-onset hypertension in general Chinese adults, with an inflection point at about 10.9 mg/day. [ABSTRACT FROM AUTHOR]

4.3 (400.0 mg) which was purified by Sephadex LH-20 (MeOH-H SB 2 sb O, 5:5) and semipreparative HPLC (CH SB 3 sb CN-H SB 2 sb O, 11:9). SP 1 sp H NMR (400 MHz, CDCl SB 3 sb , , ppm, J/Hz): 7.06 (2H, d, J = 8.4, H-2', 6'), 6.85 (2H, d, J = 8.4, H-3', 5'), 6.48 (1H, d, J = 11.6, H-20), 5.88 (1H, ddd, J = 15.0, 9.9, 2.2, H-13), 5.60 (1H, d, J = 11.6, H-19), 5.21 (1H, ddd, J = 15.0, 10.9, 3.8, H-14), 4.38 (1H, br.s, H-7), 3.77 (3H, s, 4'-OCH SB 3 sb ), 3.70 (1H, m, H-3), 2.99 (1H, dd, J = 5.2, 2.6, H-4), 2.93 (1H, ddd, J = 11.6, 6.8, 2.2, H-16), 2.83 (1H, dd, J = 13.7, 4.6, H-10a), 2.65 (1H, d, J = 4.6, H-10b), 2.62 (1H, overlapped, H-15a), 2.60 (1H, overlapped, H-8), 2.27 (1H, dd, J = 7.4, 5.2, H-5), 2.14 (1H, m, H-15b), 1.47 (3H, s, H-23), 1.25 (3H, s, H-12), 1.15 (3H, d, J = 6.8, H-22), 1.08 (3H, d, J = 7.4, H-11). SP 1 sp H NMR (400 MHz, DMSO-d SB 6 sb , , ppm): 9.19 (1H, s, 2-NH), 8.08 (1H, s, 4'-OH), 6.95 (2H, d, J = 8.4, H-2', 6'), 6.67 (2H, d, J = 8.4, H-3', 5'), 6.33 (1H, d, J = 12.7, H-20), 5.60 (1H, overlapped, H-19), 5.57 (1H, overlapped, H-13), 5.33 (1H, ddd, J = 15.2, 10.8, 4.3, H-14), 5.26 (1H, d, J = 2.2, H-7), 4.03 (1H, q, J = 7.1, H-3), 3.32 (1H, m, H-18), 2.93 (1H, m, H-4), 2.88 (1H, d, J = 9.2, H-8), 2.74 (2H, m, H-10), 2.71 (1H, m, H-16), 2.68 (1H, m, H-5), 2.46 (1H, m, H-15a), 2.03 (1H, m, H-15b), 1.67 (3H, s, H-12), 1.16 (3H, d, J = 6.9, H-22), 1.11 (3H, d, J = 6.8, H-23), 0.70 (3H, d, J = 7.2, H-11). [Extracted from the article]

Background: Postoperative abdominal adhesions (PAAs) represent a frequent condition occurring in more than 90% of patients undergoing abdomen and pelvic surgeries, which can cause chronic abdominal pain, female infertility, and repeated bowel obstruction, requiring repetitive surgical interventions causing morbidity and mortality, as well as high costs. It is therefore of paramount clinical importance and significance to develop practical and reliable strategies for preventing the occurrence of PAAs. Methods and Results: In this study, we demonstrated that Nianfukang (NFK, composed of polyethylene glycol 1450 and diclofenac sodium) is highly effective in preventing PAAs, likely by reducing leukocytes and inflammatory factors in the abdominal cavity, and inhibiting intestinal fibrosis in a rat model of PAAs induced by postoperative cecum scraping. We further uncovered that NFK downregulates the expression of TGF-β1, a key factor for adhesion formation, to suppress the TGF-β1/TGF-βRIII/Smad2 signaling pathway, thereby inhibiting the proliferation and migration of fibroblasts and provided evidences for the involvement of the TGF-β1/TGF-βRIII/Smad2 axis in the prevention of PAAs in normal human colon fibroblast CCD-18Co. Conclusions: Our findings support NFK as a potential anti-adhesive product that has the advantages of significant effectiveness, safety profile, and low cost, as well as clear mechanism of action. [ABSTRACT FROM AUTHOR]

As a typical category of two-photon absorption molecules, solvent effects on dynamical properties of porphyrin were studied for picosecond pulse trains in this work. The pulse train contains 20 subpulses of 70 picoseconds width at 532 nanometers, separated by 13 nanoseconds. According to the molecular energy level distributing, porphyrin was simplified as a generalized five-level model during the nonlinear optical process, and the two-step TPA is the main absorption tunnel. In the theoretical simulation, we used Crank–Nicholson numerical method to solve entangled equations of two-dimensional paraxial field and the rate equations. Interacting with picosecond pulse trains, meso-tetrakis (methylpyridiniumyl) porphyrin (TMPyP) in aqueous and in several organic solvents shows excellent optical limiting behaviors. Besides water, negatively charged sodium dodecylsulfate, protonic methyl, ethyl and propyl alcohols and aprotic acetonitrile were considered as the solvents. Our results show that TMPyP in water has the lowest energy transmittance, which is mainly due to the formatted hydrogen bonds of nitrogen atom in TMPyP to water. [ABSTRACT FROM AUTHOR]

Purpose: Increasing evidences have revealed the anti-cancer effect of disulfiram. Current disulfiram-based cancer therapies still have limitations, such as poor tumor-targeting ability and insufficient studies on anti-tumor mechanisms. Methods: In the present study, tumor-targeting liposomes were prepared as drug carriers to increase retention of disulfiram in tumor cells. Then, anti-tumor efficacy of liposomes and the underlying mechanisms were investigated in in vitro, in vivo, and transcriptomic level. Results: The results showed that disulfiram enhanced sensitivity of human hepatocellular carcinoma cells to doxorubicin by 15–27-fold, and increased reactive oxygen species (ROS) production as well as caspase-dependent apoptosis. Inhibition of tumor migration and invasion by doxorubicin were further enhanced by disulfiram. In vivo study showed that disulfiram additive doxorubicin liposomes had better performance in suppressing tumor growth than single doxorubicin liposomes. Gene expression profiling found that cellular components destruction, cell stress, check point regulation, and immunoregulation were the main anti-tumor mechanisms of disulfiram. More importantly, disulfiram possessed a great potential to be a protein ubiquitination and murine double minute 4 (MDM4) targeting compound. Conclusions: Due to its low price and good safety, it is worth to repurposing disulfiram as a chemotherapeutic drug. Furthermore, MDM4 may act as a biomarker for observation the clinical effect of disulfiram-based treatment. [ABSTRACT FROM AUTHOR]

To suppress the accumulation of δ-ferrite and adjust the dilution of the Al-Si coating, 22MnB5 coated with Al-Si was laser lap welded with filler wire. The weld appearance, dilution of the coating, microstructure, and mechanical properties of the joints were studied. A mathematical model was established by energy conservation between the feeding speed and weld appearance and between the feeding speed and dilution of the base material. When the feeding speed was raised, the weld gradually changed from a tall cup shape to a bowl shape and the dilution of the coating decreased. This led to the reduction of the δ-ferrite. The fusion zone (FZ) was lath-like martensite (M). Four zones along the FZ to base material (BM) were formed in HAZ. The coarse grain heat-affected zone (CGHAZ) near FZ and the fine grain heat-affected zone (FGHAZ) consisted of martensite. The intercritical heat-affected zone (ICGHAZ) near BM consisted of martensite and a small amount of ferrite. The tempered zone (TZ) consisted of tempered martensite with the lowest hardness. Importantly, band-like (δ-ferrite) which had low strength and ductility occurred along the fusion boundary and became a weak region. The ultimate tensile strength was only 436 MPa without filler wire but reached 746 MPa with filler wire whose failure mode mixed dimpled and quasi-cleavage fracture. [ABSTRACT FROM AUTHOR]

Ti-6Al-4V alloy was brazed in vacuum using self-designed and non-copper Ti-38Zr-24Ni (wt.%) filler metal. The microstructural evolution and mechanical properties of the joints were researched. Ni and Zr atoms diffused into based material and led to β-Ti transformation, which formed the diffusion zone. Its microstructure was α-Ti and (Ti, Zr)2Ni eutectoid structures and remained based material. The interface zone was formed through isothermal solidification, which was composed of α-Ti and (Ti, Zr)2Ni by eutectoid transformation. The center zone was comprised of big block brittle (Ti, Zr)2Ni IMCs and some tiny phases: α-Ti and (Ti, Zr)2Ni by hypoeutectic and following eutectoid transformation. The maximum shear strength was 673MPa at 930°C for 45 min. The weak area was the center zone. Cracks initiated and propagated in the brittle (Ti, Zr)2Ni IMCs in the center zone and may be hindered by α-Ti which exhibited the mixed quasi-cleavage and cleavage fractures. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to identify the ferroptosis induced tumor microenvironment (FeME) landscape in bladder cancer (BCa) for mRNA vaccine development and selecting suitable patients for precision treatment. Methods: Gene expression profiles and clinical information of 1216 BCa patients were extracted from TCGA-BLCA, three GEO databases and IMvigor210 cohort. We comprehensively established the FeME landscape of 1216 BCa samples based on 290 ferroptosis related genes (FRGs), and systematically correlated these regulation patterns with TME cell-infiltrating characteristics. Besides, we identified the patients' ferroptosis risk index (FRI) to predict the prognosis of BCa for precise treatment. Results: Six over-expressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in BCa. Furthermore, we demonstrated the evaluation of FeME within individual tumors could predict stages of tumor inflammation, subtypes, genetic variation, and patient prognosis. Then, 5-lncRNA signature was mined to produce the FRI. Low FRI was also linked to increased mutation load, better prognosis and enhanced response to anti-PD-L1 immunotherapy. Besides, an immunotherapy cohort confirmed patients with lower FRI demonstrated significant therapeutic advantages and clinical benefits. Conclusions: TFRC, SCD, G6PD, FADS2, SQLE, and SLC3A2 are potent antigens for developing anti-BCa mRNA vaccine. Establishment of FRI will contribute to enhancing our cognition of TME infiltration characterization and guiding more effective immunotherapy strategies and selecting appropriate patients for tumor vaccine therapy. [ABSTRACT FROM AUTHOR]

The reaction process of gaseous 1,3-butadiene following ultraviolet irradiation at the temperature range from 298 to 323 K under nitrogen atmosphere was monitored by UV–vis spectrophotometry. A gaseous mini-reactor was used as a reaction vessel and could be directly monitored in a UV–vis spectrophotometer. We investigated the reactivity and kinetics of 1,3-butadiene under non-UV and UV irradiation to evaluate its photochemical stability. A second-order kinetic model with 50.48 kJ·mol–1 activation energy fitted the reaction data for non-UV irradiation, whereas a first-order kinetic model was appropriate in the case of UV irradiation with activation energies of 19.92–43.65 kJ mol–1. This indicates that ultraviolet light could accelerate the photolysis reaction rate of 1,3-butadiene. In addition, the reaction products were determined using gas chromatography-mass spectrometry (GC–MS), and the reaction pathways were identified. The photolysis of 1,3-butadiene gave rise to various volatile products by cleavage and rearrangement of single C–C bonds. The differences between dimerization and dissociation of 1,3-butadiene under ultraviolet irradiation were elucidated by combining experimental and theoretical methods. The present findings provide fundamental insight into the photochemistry of 1,3-butadiene compounds. [ABSTRACT FROM AUTHOR]

Laser welding of Al-Si coated 22MnB5 hot stamping steel/galvanized steel with different laser power, welding speed, and coating conditions were presented. The weld appearance, microstructure, and mechanical properties of the joints were investigated. With the increase of heat input (raising the laser power or lowering the welding speed), the welding seam changed from Y-shape to X-shape gradually, and the widths of the weld seam increased. The fusion zone (FZ) consisted of lath martensite (M). On the side of 22MnB5, the heat-affected zone (HAZ) was divided into coarse grain zone, refined zone, intercritical zone, and tempered zone along the direction from FZ to the base material (BM). Coarse grain zone and refined zone comprised martensite, intercritical zone comprised martensite and a little ferrite, and tempered zone comprised tempered martensite, which expressed obvious softening. On the side of galvanized steel, HAZ was mainly composed of ferrite and pearlite. Significantly, band-like δ-ferrite (a low ductility and low strength phase) was formed along the fusion boundary owing to the accumulation of the mixing of Al-Si coating and base metals. The maximum tensile shear strength of the joint was only 484 MPa in coated condition but increased to 700 MPa in de-coated condition because of the existence of δ-ferrite along the fusion boundary, which deteriorated the mechanical properties of the joints. The failure occurred at the fusion boundary (FB) in the coated conditions with a mixture of cleavage, quasi-cleavage, and dimpled fracture. However, the failure occurred at the interface in the de-coated condition with a dimpled fracture. In addition, for the coated condition, higher laser power or lower welding speeds led to wider bead width and more intense weld pool flow, which enhanced the diffusion of Al, resulted in alleviating the accumulation of Al at the fusion boundary, which increased the mechanical properties. [ABSTRACT FROM AUTHOR]

Herein, we report on the isolation and anti-inflammatory activities of these compounds. Compound B 6 b showed significant anti-inflammatory activity by inhibiting the production of NO in LPS-induced RAW 264.7 cells with IC SB 50 sb value of 23.24 ± 1.3 M (indomethacin IC SB 50 sb 33.50 ± 1.13 M), the other compounds showed no obvious anti-inflammatory activity ( B 1-5 b , IC SB 50 sb > 50 M). Among them, compound B 4 b was isolated from genus I Xylaria i firstly I , i and the other compounds were isolated from I Xylaria grammica i for the first time. Graph All compounds were tested for their anti-inflammatory activities [[4], [20]]. [Extracted from the article]

Introduction: Small cell lung cancer (SCLC) is known for its rapid clinical progression and poor prognosis. In this study, we sought to establish a prognostic nomogram among SCLC patients who received chemotherapy. Methods: We obtained 4971 SCLC patients' clinical information from the Surveillance, Epidemiology, and End Results (SEER) database for the period between 2004 and 2015. Patients were divided into training and validation sets. Two nomograms were established based on limited stage (LS) and extensive stage (ES) SCLC patients to predict 1-, 2-, and 3-year overall survival (OS) incorporating superior parameters from multivariate Cox regression. Receiver-operating characteristic curves (ROCs) were applied to assess the discrimination ability of the nomogram while the calibration plots were applied to verify the model. Kaplan-Meier method was applied to find survival curves. Decision curve analysis (DCA) was applied to compare OS between the nomograms and 7th American Joint Committee on Cancer (AJCC) tumor node metastasis (TNM) staging system. Results: Four and six clinical parameters were identified as significant prognostic factors for LS-SCLC and ES-SCLC patient's OS, respectively. The ROC curves indicated satisfactory discrimination capacity of the nomogram, with 1-, 2-, and 3-year area under curve (AUC) values of 0.89, 0.81, and 0.79 in LS-SCLC patients and 0.71, 0.66, and 0.66 in ES-SCLC patients, respectively. Calibration curves indicated that the nomogram showed good agreement with actual observations in survival rate probability. The survival curves among the LS-SCLC and ES-SCLC cohorts were consistent with the high-risk group having a worse prognosis than the low-risk group. Moreover, ROC and DCA curves showed our nomograms had more benefits than the 7th AJCC-TNM staging system. Conclusions: We established two nomograms that can present individual predictions of OS among LS-SCLC and ES-SCLC patients who received chemotherapy. These proposed nomograms may aid clinicians in treatment strategy and design of clinical trials. [ABSTRACT FROM AUTHOR]

Blend films with poly(ε-caprolactone)(PCL) and poly(propylene carbonate)(PPC)with thickness of approximately 40 μm and 60 μm, respectively, were prepared using a uniaxial-stretching extrusion process to modify the property of PCL. PCL/PPC blend films with better comprehensive properties with thickness about 60 μm were used for equilibrium-modified atmosphere packaging of button mushrooms at 5 °C. The gas barrier property together with water vapor permeability were evaluated as well as its effects on the shelf life button mushrooms. The results showed that the PCL/PPC20 and PCL/PPC50 blend films have suitable gas barrier property and water vapor permeability, which was helpful to generate an appropriate storage environment and more importantly no condensation occurred in these two packages. The lower weight loss of button mushrooms was observed for PCL/PPC20 and PCL/PPC50 blend films 4.43 and 4.46, respectively. The PCL/PPC blend films was more effective in decreasing the activity of PPO and preserving the color of the button mushrooms. The over market acceptability of button mushrooms packaged in PCL/PPC blend films still maintained good and within the limit of marketability after 17 days of storage. [ABSTRACT FROM AUTHOR]

Background: Sleep deprivation (SD) has become a serious concern worldwide. This study aimed to identify key modules and candidate hub genes correlated with diseases caused by SD, using co-expression analysis. Methods: The weighted gene co-expression network analysis was performed to construct a co-expression network of hub genes correlated with SD. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to search for signaling pathways. The protein–protein interaction network analysis of central genes was performed to recognize the interactions among central genes. Molecular Complex Detection, a plugin in Cytoscape, was used to discover the hub gene clusters involved in SD. Results: A total of 564 genes in the yellow module were identified based on the results of topological overlap measure–based clustering. The yellow module showed a pivotal correlation with SD. Six hub gene clusters prominently associated with SD were identified. Heat shock protein family and circadian clock genes among them may be the hub genes involved in SD. Conclusions: These genes and pathways might become therapeutic targets with clinical usefulness in the future. [ABSTRACT FROM AUTHOR]

Rationale: MicroRNAs (miRNAs) regulate neuroplasticity-related proteins and are implicated in methamphetamine (METH) addiction. RhoA is a small Rho GTPase that regulates synaptic plasticity and addictive behaviors. Nevertheless, the functional relationship between RhoA and upstream miRNAs of METH addiction remains unclear. Objective: To explore the molecular biology and epigenetic mechanisms of the miR-31-3p/RhoA pathway in METH addiction. Methods: RhoA protein and its potential upstream regulator, miR-31-3p, were detected. A dual luciferase reporter was employed to determine whether RhoA constituted a specific target of miR-31-3p. Following adeno-associated virus (AAV)-mediated knockdown or overexpression of miR-31-3p or RhoA in the dorsal hippocampus (dHIP), mice were subjected to conditioned place preference (CPP) to investigate the effects of miR-31-3p and RhoA on METH-induced addictive behaviors. Results: RhoA protein was significantly decreased in the dHIP of CPP mice with a concomitant increase in miR-31-3p. RhoA was identified as a direct target of miR-31-3p. Knockdown of miR-31-3p in the dHIP was associated with increased RhoA protein and attenuation of METH-induced CPP. Conversely, overexpression of miR-31-3p was associated with decreased RhoA protein and enhancement of METH effects. Similarly, knockdown of RhoA in the dHIP enhanced METH-induced CPP, whereas RhoA overexpression attenuated the effects of METH. Parallel experiments using sucrose preference revealed that the effects of miR-31-3p/RhoA pathway modulation were specific to METH. Conclusions: Our findings indicate that the miR-31-3p/RhoA pathway in the dHIP modulates METH-induced CPP in mice. Our results highlight the potential role of epigenetics represented by non-coding RNAs in the treatment of METH addiction. [ABSTRACT FROM AUTHOR]

Cardiac remodeling is a physiological adaptation to aerobic exercise and which is characterized by increases in ventricular volume and the number of cardiomyocytes. The mitochondrial derived peptide MOTS-c functions as an important regulator in physical capacity and performance. Exercise elevates levels of endogenous MOTS-c in circulation and in myocardium, while MOTS-c can significantly enhance exercise capacity. However, the effects of aerobic exercise combined with MOTS-c on cardiac structure and function are unclear. We used pressure–volume conductance catheter technique to examine cardiac function in exercised rats with and without treatment with MOTS-c. Surprisingly, MOTS-c improved myocardial mechanical efficiency, enhanced cardiac systolic function, and had a tendency to improve the diastolic function. The findings suggest that using exercise supplements could be used to modulate the cardiovascular benefits of athletic training. [ABSTRACT FROM AUTHOR]

Introduction: The coronavirus disease 2019 (COVID-19) was defined as a species of beta coronavirus causing atypical respiratory disease in humans. The COVID-19 pandemic has resulted in an unprecedented health and economic crisis worldwide. Little is known about the specifics of its influence on people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (PLWHA). In this study, we aim to investigate the prevalence and mortality in PLWHA co-infected with COVID-19. Methods: The databases PUBMED, EMBASE, BioRxiv, and medRxiv were searched up to 9 March 2021 to explore the prevalence and mortality rate of COVID-19 in PLWHA. Cohort studies and case series meeting the inclusion criteria were included in this review. Results: We identified 14 eligible studies, 9 of which were cohort and 5 were case series. A total of 203,761 patients with COVID-19 were identified (7718 PLWHA vs. 196,043 non-PLWHA). Meta-analyses estimated the prevalence and mortality rate of COVID-19 in PLWHA was 0.774% [95% confidence interval (CI) 0.00393–0.01517] and 8.814% (95% CI 0.05766–0.13245) respectively. COVID-19 co-infected PLWHA do not seem to be associated with higher mortality, as compared to non-PLWHA [relative risk (RR) 0.96 (95% CI 0.88–1.06)]. The presence of comorbidities such as diabetes mellitus, RR 5.2 (95% CI 4.25–6.36), hypertension and chronic cardiac disease, RR 4.2 (95% CI 1.09–16.10), and chronic kidney disease, RR 8.43 (95% CI 5.49–12.93) were associated with an increased mortality in COVID-19 co-infected PLWHA. Conclusion: The estimated prevalence and mortality rate of COVID-19 in PLWHA were 0.774% and 8.814%, respectively. Since most of the included studies used unmatched populations, comparisons between PLWHA and non-PLWHA should be interpreted with caution. Further investigations are needed for a more comprehensive understanding of the relationship between cluster of differentiation 4 cell count, HIV viral load, antiretroviral therapy, and COVID-19 related prognosis in PLWHA. [ABSTRACT FROM AUTHOR]

Aims: The association between estimated glomerular filtration rate (eGFR) and the risk of diabetes remains uncertain. We aimed to examine the association between eGFR based on creatinine (eGFRcr), cystatin C (eGFRcys), or a combination of both (eGFRcr-cys) and new-onset diabetes, using data from the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative cohort study. Methods: A total of 4,775 participants with pertinent measurements and without diabetes at baseline from CHARLS were included in the final analysis. The eGFR was calculated by creatinine, cystatin C or a combination of both using the Chronic Kidney Disease Epidemiology Collaboration equations. The study outcome was new-onset diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥ 126 mg/dL, random glucose ≥ 200 mg/dL, or HbA1c ≥ 6.5% (48 mmol/mol) at the exit visit. Results: The mean age of the study population was 59.6 years. The mean values for the eGFRcr, eGFRcys, and eGFRcr-cys were 92.4, 78.9 and 85.9 mL/min/1.73m2, respectively. Over 4 years of follow-up, 612 (12.8%) participants experienced diabetes. Participants with lower eGFRcr-cys (< 60 mL/min/1.73m2) had a significantly higher risk of new-onset diabetes (adjusted OR, 1.46; 95%CI: 1.02, 2.09), compared to those with eGFRcr-cys ≥ 60 mL/min/1.73m2. However, there was no significant association between eGFRcr (< 60 vs. ≥ 60 mL/min/1.73m2; adjusted OR, 1.27; 95%CI: 0.75, 2.17) or eGFRcys (adjusted OR, 1.04; 95%CI: 0.80, 1.36) and new-onset diabetes. Conclusions: Lower eGFRcr-cys (< 60 mL/min/1.73m2), but not eGFRcr or eGFRcys, was significantly associated with an increased risk of new-onset diabetes in Chinese adults. [ABSTRACT FROM AUTHOR]

Accurately identifying and differentiating the types of injuries in decomposed corpses is a major challenge in forensic identification. Forensic investigations involving decomposed cadavers pose challenges in determining the cause of death. Traditional methods often lack conclusive evidence. However, the implementation of advanced analytical techniques, such as comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC × GC-TOF/MS), shows promise in overcoming these limitations, but the potential in this area remains limited. Therefore, this study aims to bridge this gap by exploring the potential of GC × GC-TOF/MS in the analysis of volatile organic compounds (VOCs) changes within decaying ante- and post-mortem injuries.The research emphasizes the forensic significance of VOCs changes in decomposed cadavers. We used GC × GC-TOF/MS analysis to identify the specific volatile compounds in putrefied corpse tissue samples from mice. The GC × GC-TOF/MS analysis results showed that under winter conditions, PC1 explained 57.16% of the variance, and PC2 explained 25.23% of the variance; while under summer conditions, PC1 explained 71.89% of the variance, and PC2 explained 24.49% of the variance. This demonstrates the potential of GC × GC-TOF/MS in identifying specific VOCs present in tissue samples that can serve as potential biomarkers for distinguishing between antemortem and postmortem injury. GC × GC-TOF/MS analysis revealed distinct VOC patterns in both conditions. Comprehensive use of GC × GC-TOF/MS analysis enhances accuracy in identifying and characterizing ante- and post-mortem injuries in decomposed cadavers. This study can significantly contribute to the field of forensic medicine and improve the accuracy of forensic investigations. [ABSTRACT FROM AUTHOR]

This article explores the development and challenges of forensic medicine in Africa, comparing it to developed countries. It addresses limited resources, funding, and a shortage of trained professionals. The growth of forensic investigation capabilities and the challenges of funding and technology access are discussed. Training and education have improved, but disparities remain. Partnerships with developed countries and international organizations are crucial to bridge the gap. A comprehensive legal framework is important, but disparities exist among African countries. Harmonizing forensic laws would enhance cooperation. The role of forensic medicine in the criminal justice system is examined, emphasizing the need to build trust in forensic evidence. International collaboration and capacity building are key to advancing forensic medicine in Africa. Investments in infrastructure, funding, training, and legal frameworks are required. By leveraging partnerships, Africa can develop its forensic medicine capabilities for a fair and effective criminal justice system. [ABSTRACT FROM AUTHOR]