Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations.

Herein, we report a pair of regioselective N 1- and N 2 -alkylations of a versatile indazole, methyl 5-bromo-1H-indazole-3-carboxylate (6) and the use of density functional theory (DFT) to evaluate their mechanisms. Over thirty N 1- and N 2-alkylated products were isolated in over 90% yield regardless of the conditions. DFT calculations suggest a chelation mechanism produces the N 1-substituted products when cesium is present and other non-covalent interactions (NCIs) drive the N 2-product formation. Methyl 1H-indazole-7-carboxylate (18) and 1H-indazole-3-carbonitrile (21) were also subjected to the reaction conditions and their mechanisms were evaluated. The N 1- and N 2-partial charges and Fukui indices were calculated for compounds 6, 18, and 21 via natural bond orbital (NBO) analyses which further support the suggested reaction pathways.

Microorganisms Associated with the Ambrosial Beetle Xyleborus affinis with Plant Growth-Promotion Activity in Arabidopsis Seedlings and Antifungal Activity Against Phytopathogenic Fungus Fusarium sp. INECOL_BM-06.

Plants interact with a great diversity of microorganisms or insects throughout their life cycle in the environment. Plant and insect interactions are common; besides, a great variety of microorganisms associated with insects can induce pathogenic damage in the host, as mutualist phytopathogenic fungus. However, there are other microorganisms present in the insect-fungal association, whose biological/ecological activities and functions during plant interaction are unknown. In the present work evaluated, the role of microorganisms associated with Xyleborus affinis, an important beetle species within the Xyleborini tribe, is characterized by attacking many plant species, some of which are of agricultural and forestry importance. We isolated six strains of microorganisms associated with X. affinis shown as plant growth-promoting activity and altered the root system architecture independent of auxin-signaling pathway in Arabidopsis seedlings and antifungal activity against the phytopathogenic fungus Fusarium sp. INECOL_BM-06. In addition, evaluating the tripartite interaction plant-microorganism-fungus, interestingly, we found that microorganisms can induce protection against the phytopathogenic fungus Fusarium sp. INECOL_BM-06 involving the jasmonic acid-signaling pathway and independent of salicylic acid-signaling pathway. Our results showed the important role of this microorganisms during the plant- and insect-microorganism interactions, and the biological potential use of these microorganisms as novel agents of biological control in the crops of agricultural and forestry is important.

Psychometric properties of ability to contribute measurements as a domain of functional ability of older persons: a COSMIN systematic review.

BACKGROUND: Older person's ability to contribute covers contributions divided into five subdomains: assisting friends and neighbours, mentoring peers and younger people, caring for family, engaging in the workforce and voluntary activity. OBJECTIVE: To evaluate the psychometric properties of ability to contribute measurements as a domain of functional ability of older persons using Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) methodology for systematic reviews. METHODS: A systematic search was performed in PubMed, Embase and PsycINFO databases, for observational studies published within the last 10 years. The measurement properties of these ability measures were evaluated against the COSMIN taxonomy. Risk-of-bias assessment was performed using the COSMIN Risk of Bias checklist. RESULTS: Of the 32,665 studies identified, we selected 19, of which the main purpose was to develop or validate an instrument or have related items that measure at least one of the subdomains. None of the instruments contained items that were fully related to the five subdomains, 60% (n = 12) were related to voluntary activities and 15% (n = 3) to mentoring peers and younger people. As for psychometric properties, two studies assessed content validity. Factor analysis was used to evaluate structural validity in 10 studies. Internal consistency was evaluated in 63% of the instruments and Cronbach's alpha ranges from 0.63 to 0.92. No study reported predictive validity. A very limited overview of their scope and limitations for their application was observed. CONCLUSIONS: We found no single instrument measuring all subdomains of ability to contribute. We found several instruments containing items that could indirectly measure some of the subdomains of the ability to contribute.

Association of loneliness and social isolation with all-cause mortality among older Mexican adults in the Mexican health and aging study: a retrospective observational study.

BACKGROUND: Plenty of evidence shows how social isolation and loneliness are associated with increased risk for numerous diseases and mortality. But findings about their interactive or combined effects on health outcomes and mortality remains inconclusive. OBJECTIVE: Analyze the longitudinal association of loneliness, social isolation and their interactions, with the all-cause mortality among older adults in Mexico. METHODS: A retrospective observational study was conducted. Mexican adults older than 50 years were included. Data from the Mexican Health and Aging Study (MHAS) in the 2015 and 2018 waves were used. The subjects were classified according to their level of loneliness and the presence of social isolation. Multivariate logistic regression analyzes were performed to determine the degree of association between loneliness and social isolation with all-cause mortality at a 3-year follow-up. RESULTS: From the total sample of 11,713 adults aged 50 years or over, 707 (6%) did not survive, 42% presented loneliness, and 53% were classified as socially isolated. After multivariate adjustment only social isolation (OR = 1.30, 95%CI:1.03-1.64) was associated with all-cause mortality, loneliness (Mild: OR = 0.83, 95%CI:0.59-1.16; Severe: OR = 1.03, 95%CI:0.71-1.64), and the interaction between loneliness and social isolation were not associated with all-cause mortality. CONCLUSION: Social isolation, but not loneliness or their interaction, was associated with all-cause mortality in Mexican adults older than 50 years. This finding may help direct possible future interventions that help improve mental health in older adults from a highly collectivistic country.

Antifungal and Insecticidal Activities of Selected Plant Species from Cloud Forest of Veracruz, Mexico: A Contribution to the Search of Novel Control Agents against Ambrosia Pest Complexes.

The antifungal and insecticidal activities of 34 extracts from 27 plant species were evaluated against fungal phytopathogens of the genus Fusarium and Xyleborus Scolytine ambrosia beetles involved in Fusarium dieback (FD) and laurel wilt (LW) diseases. Sixteen extracts caused mycelial growth inhibition (MGI) above 23 % at 2 mg mL-1 against F. solani, those from S. nudum and M. argyrophylla exhibited the highest MGI (57 % and 49 %, respectively). Thirteen extracts displayed significant antifungal activity against F. kuroshium, those from C. nocturnum and M. argyrophylla exhibited the highest MGI (100 % and 54.9 %, respectively). Additionally, ten plants extracts caused mortality in at least one of the beetle species tested, mainly from Solanaceae species. In the most active species, 39 phenolics were identified that may have contributed to their biological effects. This study is one of the first to report the potential of plant-derived natural products against the causative agents of FD and LW.

Discovery and optimization of orally bioavailable and potent plasma Kallikrein inhibitors bearing a quaternary carbon.

Hereditary angioedema (HAE) is a rare and potentially life-threatening disease that affects an estimated 1 in 50,000 individuals worldwide. Berotralstat (BCX7353) is the only small molecule approved by the US Food and Drug Administration (FDA) for the prophylactic treatment of HAE attacks in patients 12 years and older. During the discovery of BCX7353, we also identified a novel series of small molecules containing a quaternary carbon as potent and orally bioavailable Plasma Kallikrein (PKal) inhibitors. Lead compound was identified as a potent inhibitor following a detailed lead optimization process that balanced the lipophilic efficiency (LipE) and pharmacokinetic (PK) profile.

Scaffold hopping via ring opening enables identification of acyclic compounds as new complement Factor D inhibitors.

The three complement pathways comprising the early phase of the complement system (the classical, lectin, and alternative pathways) act together with the innate and adaptive immune systems to protect against foreign entities and maintain tissue homeostasis. While these systems are normally under tight regulatory control, several diseases have been reported to correlate with uncontrolled activation and amplification of the alternative pathway, including paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, C3 glomerulopathy, and age-related macular degeneration. Complement FactorD (CFD), a serine protease, is the rate-limiting enzyme for the activity of alternative pathway. CFD activates the alternative pathway by cleaving Complement Factor B complexed to C3b (C3bB) to generate alternative pathway C3 convertase (C3bBb). In our search for novel CFD inhibitors with therapeutic potential, we employed a hot-spot analysis of an ensemble of apo and holo CFD structures. This analysis identified potential pharmacophore features that aided in the design of a series of compounds based on an l-proline core. While these compounds inhibited CFD in an esterolytic assay (for example, a proline-based compound, IC50 = 161 nM), the pharmacokinetic (PK) properties were poor. A strategy of scaffold hopping via ring opening led to a novel series of acyclic compounds, with subsequent structure-based ligand design and lead optimization producing several novel CFD inhibitors. One of these inhibitors, 1-(2-((2-(3-chloro-2-fluorobenzylamino)-2-oxoethyl)(cyclopropyl)amino)-2-oxoethyl)-5-(3-methyl-3-(1-methylpiperidin-4-yl)ureido)-1H-indazole-3-carboxamide, showed good potency with IC50s of 37 nM in the esterolytic assay and 30 nM in a hemolytic assay and PK assessments following oral administration to rats revealed a Cmax of 113 ng/mL and an AUC0-24h of 257 hr.ng/mL.

Variability in case fatality rate risk due to Covid-19 according to health services provider in Mexico City hospitals.

OBJECTIVE: To describe differences in Case Fatality Rate (CFR) for Covid-19 among healthcare subsystems in Mexico City between March and December 2020. MATERIALS AND METHODS: This is a retrospective secondary data analysis from the National Epidemiological Surveillance System data of Covid-19 cases. Information about health provider institutions was retrieved from the Catalogue of Health Establishments (CLUES). Logistic regressions were fitted to determine the association between health subsystems and mortality associated to Covid-19. The analyses were divided between hospitalized and ambulatory patients. RESULTS: The probability of dying from Covid-19 was higher among those treated at Instituto Mexicano del Seguro Social (IMSS) (Hospitalized:OR=5.11, Ambulatory:OR=36.57), Instituto de Se-guridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE) (Hospitalized:OR=2.10, Ambulatory:OR=9.19), Secretaría de Salud (SS) (Hospitalized:OR=1.94, Ambulatory:OR=5.29) or other public institutions (Hospitalized: OR=1.70, Ambulatory:OR=9.56) than in those treated in private in-stitutions. CONCLUSIONS: Differences in healthcare quality and access between health subsystems are profound. It is imperative to increase the capacity and quality of the different health subsystems to improve health outcomes.

In response to the comment on the article "Variability in case fatality rate risk due to Covid-19 according to health services provider in Mexico City hospitals"

Not available.

[Opportunity cost approximation of underage caregivers in Mexico]. / Aproximación al costo de oportunidad de los cuidadores menores de edad en México.

OBJECTIVE: To calculate the cost assumed by society for having underaged individuals who do not study and provide care to dependent older adults. MATERIALS AND METHODS: The Mexican Health and Ageing Study (MHAS) 2015 was used to calculate the number of underage caregivers who do not attend school. The Household Income and Expenditure Survey (ENIGH) 2018 was used to estimate wage differences between populations of working age with complete elementary and complete high school education. Those differences were then converted to present value, added, and multiplied by the number of underage caregivers. RESULTS: The total annual cost of having underage caregivers who drop out of school adds to 1 112 179 210 pesos. CONCLUSIONS: The topic concerning underage caregivers has not received enough attention from specialized literature, and there is still a large research gap in this area.

Modeling the impact of temperature on the population abundance of the ambrosia beetle Xyleborus affinis (Curculionidae: Scolytinae) under laboratory-reared conditions.

Modeling the impact of temperature on each life stage of a beetle population represents a continuing challenge. This study evaluates the effects of five temperature treatments (20, 23, 26, 29 and 32 °C) on population abundance and timing of a colony of ambrosia beetles Xyleborus affinis reared under laboratory conditions and use this data to develop demographic and phenological models. Abundances at each life stage (eggs, larvae, pupae and adult) were examined through periodic destructive sampling; given that it was not possible to track individuals. To assess the effects of temperature on oviposition, development and survival rates we developed a novel estimation strategy based on cohorts, which does not require individual developmental data. Since oviposition was entirely unwitnessed, we assessed competing empirical ovipositional models. Rates of development were computed using a modal rate curve for each life stage, and rates were projected to cohorts in life stages assuming log-normal developmental variance. Temperature-driven survival rates were assumed to be logistic with a quadratic exponent to capture modal temperature dependence. Parameters were estimated simultaneously using minimum negative log posterior likelihood, assuming Poisson distribution of observations and using priors to inform unobserved developmental rates and enforce mechanistic constraints on oviposition models. A parabolic function best described oviposition rate. Optimal developmental temperatures were 30.5 °C, 29 °C and 27.5 °C, with maximum developmental rates of 0.26/day, 0.12/day and 0.23/day for eggs, larvae and pupae, respectively. The survival rates in the range 20-29 °C were equal to 1 in the eggs-to-larvae transition, from 0.72 to 0.35 in larvae-to-pupae transition, and from 0.2 to 0.89 in pupae-to-adults transition. This procedure effectively characterized the direct thermal effects on development and survival of each life stage in the X. affinis under laboratory conditions and would be suitable for estimating temperature dependence for other species in which individual observations are not possible.

Synthesis and Insecticidal Evaluation of Chiral Neonicotinoids Analogs: The Laurel Wilt Case.

Xyleborus sp beetles are types of ambrosia beetles invasive to the United States and recently also to Mexico. The beetle can carry a fungus responsible for the Laurel Wilt, a vascular lethal disease that can host over 300 tree species, including redbay and avocado. This problem has a great economic and environmental impact. Indeed, synthetic chemists have recently attempted to develop new neonicotinoids. This is also due to severe drug resistance to "classic" insecticides. In this research, a series of neonicotinoids analogs were synthesized, characterized, and evaluated against Xyleborus sp. Most of the target compounds showed good to excellent insecticidal activity. Generally, the cyclic compounds also showed better activity in comparison with open-chain compounds. Compounds R-13, 23, S-29, and 43 showed a mortality percent of up to 73% after 12 h of exposure. These results highlight the enantioenriched compounds with absolute R configuration. The docking results correlated with experimental data which showed both cation-π interactions in relation to the aromatic ring and hydrogen bonds between the search cavity 3C79 and the novel molecules. The results suggest that these sorts of interactions are responsible for high insecticidal activity.

Xyleborus volvulus (Coleoptera: Curculionidae): Biology and Fungal Associates.

The ambrosia beetle Xyleborus volvulus Fabricius has been reported as a potential vector of the plant pathogen Raffaelea lauricola T.C. Harr., Fraedrich & Aghayeva that is affecting avocado orchards in South Florida. In this study, we examined its life cycle, process of gallery formation, gallery structure, and fungal associates by rearing one generation on avocado sawdust medium under control conditions. The adult foundress excavated a vertical tunnel that constituted the main gallery with a length of 2.5 cm, followed by the construction of up to six secondary galleries with a total length of 4.4 cm. The time period for one generation (egg to adult) was 28 days. Teneral males emerged 3 days after the emergence of the first females. The F1 generation did not significantly contribute to gallery expansion. Four species of Raffaelea and nine yeast species were recovered from galleries and beetles. Raffaelea arxii and Candida berthetii were the most frequent symbionts recovered from new adults and galleries. Candida berthetii dominated during the early stages of the gallery development, whereas R. arxii was most frequent in later stages. Other Raffaelea species were inconsistently isolated from galleries, which suggests a strong association between Xyleborus volvulus and both R. arxii and C. berthetii These results suggest that R. arxii is the primary nutritional symbiont of X. volvulus and that yeast species may be pioneer colonizers that assist with the growth of fungal symbionts.IMPORTANCE Ambrosia beetles cultivate fungi in tunnels bored into weakened host trees. This obligate interaction is required for their survival as beetles feed on these symbiotic fungi, and the fungi benefit from transportation by the beetles. Xyleborus volvulus carries many nonpathogenic symbionts; however, recently the acquisition of Raffaelea lauricola (the causal agent of a lethal vascular disease of lauraceous trees) by this beetle has altered its status from wood degrader to potential pest in avocado. We conducted a study to understand the relationship of this beetle and its fungal associates. Our results show that X. volvulus has a multipartite flexible association with different Raffaelea species. The lack of fidelity in the mutualistic association may explain the acquisition of R. lauricola Knowing the beetle biology and its mutualistic interactions furthers an understanding of the beetle's role as a potential vector and in disease transmission.

A novel process of the isolation of nitrifying bacteria and their development in two different natural lab-scale packed-bed bioreactors for trichloroethylene bioremediation.

Trichloroethylene (TCE) is a carcinogenic compound that is commonly present in groundwater and has been detected in drinking water sources for Mexican towns in the Mexico-US border area. Nitrifying bacteria, such as Nitrosomonas europaea, have been shown to be capable of degrading halogenated compounds, including TCE, but it is difficult to obtain high cell concentrations of these bacteria. The aim of the present study was to generate biomass of a nitrifying bacterial consortium from the sludge of an urban wastewater treatment plant (WWTP) and evaluate its capacity to biodegrade TCE in two different natural lab-scaled packed bed bioreactors. The consortium was isolated by a novel method using a continuous stirred-tank bioreactor inoculated with activated sludge from the Domos WWTP located in Cd. Obregón, Sonora, Mexico. The bioreactor was fed with specific media to cultivate ammonia-oxidizing bacteria at a dilution rate near the maximum specific growth rate reported for Nitrosomonas europaea. Optical density and suspended solids measurements were performed to determine the culture biomass production, and the presence of inorganic nitrogen species was determined by spectrophotometry. The presence of nitrifying ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) was confirmed by PCR amplification, and biofilm formation was observed by scanning electron microscopy. Batch-scale experiments confirmed the biodegradative activity of the isolated consortium, which was subsequently fixed in an inorganic carrier as zeolite and a synthetic carrier such as polyurethane to both be used as lab-scale packed-bed bioreactors, with up to 58.63% and 62.7% of TCE biodegradation achieved, respectively, demonstrating a possible alternative for TCE bioremediation in environmental and engineering systems.

Effect of frying and storage on oxidative quality of conjugated linoleic-acid-rich soybean oil produced by photoisomerization using plantain as a model system.

BACKGROUND: Conjugated linoleic acid (CLA) is known to have beneficial properties to health. Naturally, in foods it is found in very low concentrations, and so these beneficial properties cannot be obtained. This study investigated the enrichment of soybean oil by photoisomerization, as well as assessing its oxidative stability during the frying process using plantain slices as a model system and after a storage period of 20 days at 60 °C. RESULTS: The oxidative stability of soybean oil enriched with CLA by photoirradiation was measured based on the peroxide, p-anisidine, and Totox values, as well as by the polyphenol content, tocopherol content and DPPH· scavenging capacity. The results obtained showed that a substantial amount of CLA was obtained by photoirradiation (31.73%). The oxidative stability values of the oil enriched with CLA showed good stability during a frying cycle; however, this stability decreased when it was stored and during the final frying cycles. CONCLUSIONS: The results obtained indicated that photoirradiation is a good technique for obtaining oils enriched with CLA, and in this way CLA can be incorporated into foods; however, it is necessary to add antioxidants to improve their stability. © 2019 Society of Chemical Industry.

Simulated Gastrointestinal Digestion, Bioaccessibility and Antioxidant Capacity of Polyphenols from Red Chiltepin (Capsicum annuum L. Var. glabriusculum) Grown in Northwest Mexico.

Chiltepin, a wild chili mostly used in different traditional foods and traditional medicine in Northwest Mexico, represents a source of polyphenols. However, studies about the bioaccessibility of polyphenols as a parameter to measure the nutritional quality and bioefficacy of them in the fruit after consumption are scarce. Chiltepin showed phenolic acids and flavonoids contents between 387 and 65 µg/g, respectively. Nevertheless, these values decreased after the digestion process. Before digestion, gallic acid, 4-hydroxibenzoinc acid, chlorogenic acid, caffeic acid, p-coumaric acid, quercetin and luteolin were the main polyphenols found in chiltepin by HPLC-DAD and confirmed by FIA-ESI-IT-MS/MS. Gallic and chlorogenic acids were non-detected in the gastric phase, while only p-coumaric acid (5.35 ± 3.89 µg/g), quercetin (5.91 ± 0.92 µg/g) and luteolin (2.86 ± 0.62 µg/g) were found in the intestinal phase. The bioaccessibility of phenolic acids, flavonoids, and total polyphenols after the intestinal phase was around 24, 17 and 23%, respectively. Overall, results indicated that release of polyphenols from chiltepin fruit might be affected by the food matrix and gastrointestinal conditions due to the low bioaccessibility values observed.

A team-based multidisciplinary approach to managing peripherally inserted central catheter complications in high-risk haematological patients: a prospective study.

PURPOSE: Use of peripherally inserted central catheters (PICCs) has markedly increased during the last decade. However, there are few studies on use of PICCs in patients with haematological malignancies (HM) receiving intensive chemotherapy. Preliminary data suggest a higher rate of PICC-related complications in these high-risk patients. This prospective observational single-centre study aimed to investigate PICC-related complications after implementation of a multidisciplinary approach to PICC care and compared it with previous literature. METHODS: A total of 44 PICCs were inserted in 36 patients (27.3%, thrombocytopenia <50 × 10(9)/L at insertion) over 5045 PICC days (median duration, 114.5 days). RESULTS: No major insertion-related complications were observed. Major late complications were obstruction in 13.6% (1.19/1000 PICC days) of patients, catheter-related bloodstream infection in 6.8% (0.59/1000 PICC days), and catheter-related thrombosis in 4.5% (0.39/1000 PICC days). Premature PICC removal occurred in 34% (2.97/1000 PICC days) of patients. The overall rate of potentially major dangerous complications was particularly low (11.36%, 0.99/1000 PICC days) compared with previous studies. CONCLUSIONS: This study highlights the utility of a multidisciplinary approach for PICC care in adults with HM receiving intensive chemotherapy. We provide further data to support use of PICCs in such patient populations.

Antiproliferative and apoptotic activities of extracts of Asclepias subulata.

CONTEXT: Asclepias subulata Decne. (Apocynaceae) is a shrub used in the Mexican traditional medicine for the treatment of cancer. OBJECTIVE: The objective of this study was to evaluate the antiproliferative activity of methanol extract of aerial parts of A. subulata and its fractions against different cancer cell lines. Additionally, we analyzed the mechanism of action of the active fractions. MATERIALS AND METHODS: Methanol extract fractions were prepared by serial extraction with n-hexane, ethyl acetate, and ethanol. The antiproliferative activity of methanol extract and its fractions was evaluated, against several murine (M12.C3.F6, RAW 264.7, and L929) and human (HeLa, A549, PC-3, LS 180, and ARPE-19) cell lines by the MTT assay, using concentrations of 0.4-400 µg/mL for 48 h. Ethanol and residual fractions were separated using silica gel column. Apoptosis induction of cancer cells was evaluated by Annexin and JC-1 staining using flow cytometry. RESULTS: Methanol extract and its fractions showed antiproliferative activity against all human cancer cell lines tested. Methanol extract had the highest antiproliferative activity on A549 and HeLa cells (IC50 values < 0.4 and 8.7 µg/mL, respectively). Ethanol and residual fractions exerted significant antiproliferative effect on A549 (IC50 < 0.4 µg/mL) and PC3 cells (IC50 1.4 and 5.1 µg/mL). Apoptotic assays showed that CEF7, CEF9, CRF6, and CRF5 fractions induced mitochondrial depolarization in A549 cells, 70, 73, 77, and 80%, respectively. Those fractions triggered the apoptosis mitochondrial pathway. CONCLUSION: Our data show that A. subulata extracts have potent antiproliferative properties on human cancer cell lines. This plant should be considered an important source of potent anticancer compounds.

Toll-like receptors 3, 4 and 9 in hepatocellular carcinoma: Relationship with clinicopathological characteristics and prognosis.

AIM: Hepatocellular carcinoma (HCC) is in the 10 leading cancer types, being difficult to detect as most of patients who develop this tumor have no symptoms other than those related to their long-standing liver disease. The liver is constantly exposed to bacterial products, viral infection, alcohol or other products, which may be the cause of chronic liver damage, and thus an increasing risk for HCC. Toll-like receptors (TLR) have gained an extraordinary interest in cancer research due to their role in several biological processes such as innate immune responses, the induction of adaptive immune responses, regulation of inflammation, would healing and carcinogenesis. Therefore, the aim of this study was to investigate the expression and clinical relevance of TLR3, 4 and 9 in HCC. METHODS: The expression levels of TLR3, TLR4 and TLR9 were analyzed in tumors from 30 patients with HCC. The analysis was performed by immunohistochemistry. Results were correlated with various clinicopathological findings and with overall survival. RESULTS: TLR3 was significantly high in large tumors (>4 cm in diameter) compared with small tumors (P < 0.05). Our results demonstrated that patients whose tumors showed both TLR4 and TLR9 positive immunostaining had poor prognosis. In addition, TLR9 expression by fibroblast-like cells was significantly associated with a shortened overall survival (P = 0.015). CONCLUSION: The results demonstrated an association between TLR3, TLR4 and TLR9 expression and tumor aggressiveness and poor prognosis in HCC.

Personal and Psychological Traits of University-Going Women That Affect Opportunities and Entrepreneurial Intentions.

The purpose of this research is to analyze how personality traits and psychological profiles influence the detection of entrepreneurial opportunities by, and the intentions of, university-going women in the northwest region of Mexico. It also examines how business opportunities are decisive when it comes to awakening entrepreneurial intention. The moderating and mediating effects of the detection of business opportunities and the psychological profile are also examined with respect to the direct relationship between personal traits and entrepreneurial intentions. For this study, information was collected from 1197 students attending the Autonomous University of Baja California and the Technological Institute of Sonora through a digital survey (Google Forms) distributed via email during the second half of 2022. The PLS-SEM statistical technique was used to test the hypotheses of the proposed theoretical model. The results revealed that personality traits have positive and significant effects on the psychological profile and on business opportunities. However, it was clearly observed that one's personal traits and psychological profile have little or no influence on entrepreneurial intentions. We also found that the psychological profile is the construct that most influences business opportunities. In addition, it was also highlighted that business opportunities contribute to awakening the entrepreneurial intentions of university-going women. On the other hand, it was revealed that business opportunities have a negative moderating effect on the relationship between the psychological profile and entrepreneurial intentions. Likewise, this study has shown that the detection of business opportunities and the psychological profile have indirect effects on the relationship between the personal traits and the entrepreneurial intentions of university-going women. This research contributes to the development and strengthening of trait theory, the theory of reasoned action, and the theory of planned behavior.