Exploring nature's hidden treasure: Unraveling the untapped phytochemical and pharmacological potentials of Clinopodium vulgare L. - A hidden gem in the Lamiaceae family.

Folk medicine, rooted in historical practice, has long been used for medicinal purposes, emphasizing the need to ensure the safety, quality, and efficacy of herbal medicines. This imperative has grown over time, prompting collaborative efforts to document historical records and preserve invaluable knowledge of medicinal plants. The Lamiaceae (Labiatae) family, renowned for its rich assortment of medicinal plants characterized by high concentrations of volatile oils, stands out in this regard. This review focuses on Clinopodium vulgare (C. vulgare) L., commonly known as wild basil or basil thyme, a significant species within the Lamiaceae family found across diverse global regions. C. vulgare boasts a storied history of application in treating various ailments, such as gastric ulcers, diabetes, and inflammation, dating back to ancient times. Rigorous research has substantiated its pharmacological properties, revealing its antioxidant, antiviral, antibacterial, anti-inflammatory, anticancer, antihypertensive, and enzyme-inhibitory effects. This comprehensive review provides an insightful overview of the Lamiaceae family, elucidates the extraction methods employed to obtain medicinal compounds, explores the phytoconstituents present in C. vulgare, and systematically details its diverse pharmacological properties. Additionally, the review delves into considerations of toxicity. By synthesizing this wealth of information, this study opens avenues for the potential therapeutic applications of C. vulgare. The practical value of this research lies in its contribution to the understanding of medicinal plants, mainly focusing on the pharmacological potential of C. vulgare. This exploration enriches our knowledge of traditional medicine and paves the way for innovative therapeutic approaches, offering promising prospects for future drug development. As the demand for natural remedies continues to increase, this work provides a valuable resource for researchers, practitioners, and stakeholders in herbal medicine and pharmacology.

Chiroptical Response Inversion and Enhancement of Room-Temperature Exciton-Polaritons Using 2D Chirality in Perovskites.

Although chiral semiconductors have shown promising progress in direct circularly polarized light (CPL) detection and emission, they still face potential challenges. A chirality-switching mechanism or approach integrating two enantiomers is needed to discriminate the handedness of a given CPL; additionally, a large material volume is required for sufficient chiroptical interaction. These two requirements pose significant obstacles to the simplification and miniaturization of the devices. Here, room-temperature chiral polaritons fulfilling dual-handedness functions and exhibiting a more-than-two-order enhancement of the chiroptical signal are demonstrated, by embedding a 40 nm-thick perovskite film with a 2D chiroptical effect into a Fabry-Pérot cavity. By mixing chiral perovskites with different crystal structures, a pronounced 2D chiroptical effect is accomplished in the perovskite film, featured by an inverted chiroptical response for counter-propagating CPL. This inversion behavior matches the photonic handedness switch during CPL circulation in the Fabry-Pérot cavity, thus harvesting giant enhancement of the chiroptical response. Furthermore, affected by the unique quarter-wave-plate effects, the polariton emission achieves a chiral dissymmetry of ±4% (for the emission from the front and the back sides). The room-temperature polaritons with the strong dissymmetric chiroptical interaction shall have implications on a fundamental level and future on-chip applications for biomolecule analysis and quantum computing.

Fungal Endophytes: Microfactories of Novel Bioactive Compounds with Therapeutic Interventions; A Comprehensive Review on the Biotechnological Developments in the Field of Fungal Endophytic Biology over the Last Decade.

The seminal discovery of paclitaxel from endophytic fungus Taxomyces andreanae was a milestone in recognizing the immense potential of endophytic fungi as prolific producers of bioactive secondary metabolites of use in medicine, agriculture, and food industries. Following the discovery of paclitaxel, the research community has intensified efforts to harness endophytic fungi as putative producers of lead molecules with anticancer, anti-inflammatory, antimicrobial, antioxidant, cardio-protective, and immunomodulatory properties. Endophytic fungi have been a valuable source of bioactive compounds over the last three decades. Compounds such as taxol, podophyllotoxin, huperzine, camptothecin, and resveratrol have been effectively isolated and characterized after extraction from endophytic fungi. These findings have expanded the applications of endophytic fungi in medicine and related fields. In the present review, we systematically compile and analyze several important compounds derived from endophytic fungi, encompassing the period from 2011 to 2022. Our systematic approach focuses on elucidating the origins of endophytic fungi, exploring the structural diversity and biological activities exhibited by these compounds, and giving special emphasis to the pharmacological activities and mechanism of action of certain compounds. We highlight the tremendous potential of endophytic fungi as alternate sources of bioactive metabolites, with implications for combating major global diseases. This underscores the significant role that fungi can play in the discovery and development of novel therapeutic agents that address the challenges posed by prevalent diseases worldwide.

In vitro and in silico evaluations of actinomycin X2and actinomycin D as potent anti-tuberculosis agents.

Background: Multidrug-resistant tuberculosis (MDR-TB) is one of the world's most devastating contagious diseases and is caused by the MDR-Mycobacterium tuberculosis (MDR-Mtb) bacteria. It is therefore essential to identify novel anti-TB drug candidates and target proteins to treat MDR-TB. Here, in vitro and in silico studies were used to investigate the anti-TB potential of two newly sourced actinomycins, actinomycin-X2 (act-X2) and actinomycin-D (act-D), from the Streptomyces smyrnaeus strain UKAQ_23 (isolated from the Jubail industrial city of Saudi Arabia). Methods: The anti-TB activity of the isolated actinomycins was assessed in vitro using the Mtb H37Ra, Mycobacterium bovis (BCG), and Mtb H37Rv bacterial strains, using the Microplate Alamar Blue Assay (MABA) method. In silico molecular docking studies were conducted using sixteen anti-TB drug target proteins using the AutoDock Vina 1.1.2 tool. The molecular dynamics (MD) simulations for both actinomycins were then performed with the most suitable target proteins, using the GROningen MAchine For Chemical Simulations (GROMACS) simulation software (GROMACS 2020.4), with the Chemistry at HARvard Macromolecular Mechanics 36m (CHARMM36m) forcefield for proteins and the CHARMM General Force Field (CGenFF) for ligands. Results: In vitro results for the Mtb H37Ra, BCG, and Mtb H37Rv strains showed that act-X2 had minimum inhibitory concentration (MIC) values of 1.56 ± 0.0, 1.56 ± 0.0, and 2.64 ± 0.07 µg/mL and act-D had MIC values of 1.56 ± 0.0, 1.56 ± 0.0, and 1.80 ± 0.24 µg/mL respectively. The in silico molecular docking results showed that protein kinase PknB was the preferred target for both actinomycins, while KasA and pantothenate synthetase were the least preferred targets for act-X2and act-D respectively. The molecular dynamics (MD) results demonstrated that act-X2 and act-D remained stable inside the binding region of PknB throughout the simulation period. The MM/GBSA (Molecular Mechanics/Generalized Born Surface Area) binding energy calculations showed that act-X2 was more potent than act-D. Conclusion: In conclusion, our results suggest that both actinomycins X2 and D are highly potent anti-TB drug candidates. We show that act-X2is better able to antagonistically interact with the protein kinase PknB target than act-D, and thus has more potential as a new anti-TB drug candidate.

The association of ABO blood group distribution and clinical characteristics in patients with SARS-CoV-2.

INTRODUCTION: SARS-COV-2, the novel severe acute respiratory syndrome coronavirus, has become a life-threatening public health crisis. This kind of pandemic is frightening the world with clinical, psychological, and emotional distress and leading to an economic slowdown. To explore any association between the ABO blood type and the susceptibility to coronavirus disease 2019 (COVID-19), we compared ABO blood group distribution among 671 COVID-19 patients with the local control population. METHODOLOGY: The study was conducted in Blood Bank Hospital in Erbil, Kurdistan Region, Iraq. The ABO-typed blood samples were obtained from 671 patients infected with SARS-CoV-2 between February and June 2021. RESULTS: Our results demonstrated that the risk of SARS-COV-2 was higher for patients with blood group A than those with not-A blood type patients. Of the 671 patients with COVID-19, 301 had type A (44.86%), 232 had type B (34.58%), 53 had type AB blood (7.9%), and 85 had type O (12.67%). CONCLUSIONS: We concluded that the Rh-negative blood type has a protective effect on SARS-COV-2. Our results also indicate that the decreased susceptibility of individuals with blood group O and the increased susceptibility of individuals with blood group A to COVID-19 could be linked to the presence of natural anti-blood group antibodies, particularly anti-A antibody, in the blood. However, there might be other mechanisms that require further study.

Evaluation of Renessans (Iodine Complex Molecule) Safety in Human Beings: An Open-Labeled Clinical Study.

Extensive studies on evaluation of effectiveness/toxicity of different oral doses of iodine have not been explored yet. An open-labeled phase I clinical studies were conducted using iodine complex based research compound called Renessans. Study groups were observed for development of any adverse/serious adverse events and alteration in laboratory values of vital organs, TSH and T4 hormones before and after the administration of the products. Out of 31 consented individuals, 24 healthy individuals participated in the study. Rate of occurrence of mild Adverse Events (AEs) in group A was 8.3% while in Group B it was 33.33% but these Adverse Events were self-resolving. After completion of study treatment blood serum iodine was reported to 3522.88 µg/l while mean urine iodine concentration (MUIC) was greater than 2000 µg/l. Hormonal and vital organ's testing revealed that all parameters of TSH and T4, LFT, CBC, RFT remained unaltered except from ALT-SGPT (P-value = .006) and AST-SGOT (P-value = .02). From all of these findings, it can be inferred that the use of Renessans formulations did not pose any sort of risk to human body and can be considered safe through this pilot study.

Functional interplay between antagonistic bacteria and Rhizoctonia solani in the tomato plant rhizosphere.

Microbial interactions with plant roots play an imperial role in tomato plant growth and defense against the Rhizoctonia solani. This study performed a field experiment with two antagonistic bacteria (Pseudomonas and Bacillus) inoculated in healthy and Rhizoctonia solani treated soil in tomato rhizosphere to understand the metabolic pattern and microbial function during plant disease suppression. In the present study, we assessed soil and microbial enzymes, bacterial and fungal cell forming unit (CFU), and carbon utilization profiling through Bio-Eco plates of rhizoplane samples. Antagonist bacteria and pathogen interaction significantly (p < 0.05) influenced the bacterial count, soil enzymes (chitinase and glucanase), and bacterial function (siderophore and chitinase production). These results indicated that these variables had an imperial role in disease suppression during plant development. Furthermore, the metabolic profiling showed that carbon source utilization enhanced under fruit development and ripening stages. These results suggested that carbon sources were essential in plant/pathogen/antagonist interaction. Substrates like ß-methyl-D-glucoside, D-mannitol, D-galacturonic acid, N-acetyl-D-glucosamine, and phenylethylamine strongly connect with the suppuration of root rot disease. These carbon sources may help to propagate a healthy microbial community to reduce the pathogen invasion in the plant root system, and these carbon sources can be stimulators of antagonists against pathogens in the future.

Anti-HIV Ermiasolides from Croton megalocarpus.

In recent years, elucidation of novel anti-HIV bioactive compounds from natural products is gaining importance rapidly, not only from the research and publications, but also from controlled clinical studies. Here we report three new anti-HIV eudesmane-type sesquiterpenes, 5ß-Hydroxy-8α-methoxy eudesm-7(11)-en-12,8-olide (1), 5ß,8α-Dihydroxy eudesm-7(11)-en-12,8-olide (2) and 5ß-Hydroxy-8H-ß-eudesm-7(11)-en-12,8-olide (3). These are trivially named ermiasolide A-C and were isolated from the bark of Croton megalocarpus. 5ß-Hydroxy-8α-methoxy eudesm-7(11)-en-12,8-olide (1), showed the highest anti-HIV activity by inhibiting 93% of the viral replication with an IC50 = 0.002 µg/mL. On the other hand, 5ß-Hydroxy-8H-ß-eudesm-7(11)-en-12,8-olide (3) and 5ß,8α-dihydroxy eudesm-7(11)-en-12,8-olide (2), inhibited viral replication by 77.5% at IC50 = 0.04 µg/mL and 69.5% at IC50 = 0.002 µg/mL, respectively. Molecular docking studies showed that the proposed mechanism of action leading to these results is through the inhibition of HIV-protease.

Potential of mineral-solubilizing bacteria for physiology and growth promotion of Chenopodium quinoa Willd.

Nutrient deficiency in wild plant species, including quinoa (Chenopodium quinoa Willd), can be overcome by applying mineral-solubilizing bacteria. Quinoa is a gluten-free, nutritious food crop with unique protein content. The present study aimed to characterize mineral-solubilizing rhizobacterial strains and to evaluate their plant growth-promoting potential in quinoa seedlings. More than sixty rhizobacterial strains were isolated from the quinoa rhizosphere and found eighteen strains to be strong phosphate solubilizers. Most of these bacterial strains showed zinc solubilization, and more than 80% of strains could solubilize manganese. The selected strains were identified as Bacillus altitudinis Cq-3, Pseudomonas flexibilis Cq-32, Bacillus pumilus Cq-35, Pseudomonas furukawaii Cq-40, Pontibacter lucknowensis Cq-48, and Ensifer sp. Cq-51 through 16S rRNA partial gene sequencing. Mainly, these strains showed the production of organic acids, including malic, gluconic, tartaric, ascorbic, lactic, and oxalic acids in insoluble phosphorus amended broth. All strains showed production of gluconic acids, while half of the strains could produce malic, ascorbic, lactic, and oxalic acids. These strains demonstrated the production of indole-3-acetic acid in the presence as well as in the absence of L-tryptophan. The bacterial strains also demonstrated their ability to promote growth and yield attributes, including shoot length, root length, leave numbers, root and shoot dry biomass, spike length, and spikes numbers of quinoa in pots and field trials. Increased physiological attributes, including relative humidity, quantum flux, diffusive resistance, and transpiration rate, were observed due to inoculation with mineral solubilizing bacterial strains under field conditions. P. lucknowensis Cq-48, followed by P. flexibilis Cq-32, and P. furukawaii Cq-40 showed promising results to promote growth, yield, and physiological attributes. The multi-traits characteristics and plant growth-promoting ability in the tested bacterial strains could provide an opportunity for formulating biofertilizers that could promote wild quinoa growth and physiology.

Morpho-physiological growth performance and phytoremediation capabilities of selected xerophyte grass species toward Cr and Pb stress.

Being sessile organisms, plants cannot escape unwanted changes in the environment. The rapid human population explosion caused significant environmental problems. Heavy metals produced through various sources can cause severe damage to living organisms. The study was planned to evaluate four grass species' morpho-physiological growth characteristics and phytoremediation capabilities under chromium (Cr) and lead stress (Pb) in the arid climate. Typha angustifolia, Tragus roxburghii, Aeluropus logopoides, and Cenchrus ciliaris grass species were used for the study. One-year-old stubbles from the Cholistan desert were used for the experiment. Cr treatments in the form of K2Cr2O7 were applied at 0, 20, 40, and 80 mg L-1, whereas Pb was applied as PbCl2 at 0, 50, 200, and 500 mg L-1 as control, low, moderate and high-stress, respectively. After 6 weeks of heavy metals treatments, plants were harvested and analyzed for growth performance and phytoremediation capabilities. Results depicted that, regarding morphological attributes, T. angustifolia performed better, followed by C. ciliaris; no clear pattern was observed for T. roxburghii and A. logopoides. The CO2 assimilation rate (Co2d) and water use efficiency (WUE) increased as the heavy metal stress increased in all species under both metals. In contrast, total chlorophyll content was higher under low stress. Other physiological parameters, such as relative humidity (RHd), net photosynthetic rate (A), transpiration rate (E), stomatal conductance (Gs), leaf internal CO2 concentration (Ci) and membrane stability index (MSI) gradually decreased as the Cr, and Pb stress levels increased among all the species. Moreover, Cr and Pb absorption contents of T. angustifolia were higher than the other three species at each stress level. Overall, T. angustifolia thrived against heavy metals stress and showed higher biomass, maximum photosynthetic measurements, WUE and higher metal absorption among all the selected species. Results concluded that although all the selected species behaved fine under stress conditions, T. angustifolia performance was better; thus, it can be used to remediate the soil near industrial estates.

Mitigation of salinity stress in barley genotypes with variable salt tolerance by application of zinc oxide nanoparticles.

Salinity has become a major environmental concern of agricultural lands, impairing crop production. The current study aimed to examine the role of zinc oxide nanoparticles (ZnO NPs) in reducing the oxidative stress induced by salinity and the overall improvement in phytochemical properties in barley. A total of nine different barley genotypes were first subjected to salt (NaCl) stress in hydroponic conditions to determine the tolerance among the genotypes. The genotype Annora was found as most sensitive, and the most tolerant genotype was Awaran 02 under salinity stress. In another study, the most sensitive (Annora) and tolerant (Awaran 02) barley genotypes were grown in pots under salinity stress (100 mM). At the same time, half of the pots were provided with the soil application of ZnO NPs (100 mg kg-1), and the other half pots were foliar sprayed with ZnO NPs (100 mg L-1). Salinity stress reduced barley growth in both genotypes compared to control plants. However, greater reduction in barley growth was found in Annora (sensitive genotype) than in Awaran 02 (tolerant genotype). The exogenous application of ZnO NPs ameliorated salt stress and improved barley biomass, photosynthesis, and antioxidant enzyme activities by reducing oxidative damage caused by salt stress. However, this positive effect by ZnO NPs was observed more in Awaran 02 than in Annora genotype. Furthermore, the foliar application of ZnO NPs was more effective than the soil application of ZnO NPs. Findings of the present study revealed that exogenous application of ZnO NPs could be a promising approach to alleviate salt stress in barley genotypes with different levels of salinity tolerance.

Thiourea-Capped Nanoapatites Amplify Osmotic Stress Tolerance in Zea mays L. by Conserving Photosynthetic Pigments, Osmolytes Biosynthesis and Antioxidant Biosystems.

Salinity is one of the most prevalent abiotic stresses which not only limits plant growth and yield, but also limits the quality of food products. This study was conducted on the surface functionalization of phosphorus-rich mineral apatite nanoparticles (ANPs), with thiourea as a source of nitrogen (TU-ANPs) and through a co-precipitation technique for inducing osmotic stress tolerance in Zea mays. The resulting thiourea-capped apatite nanostructure (TU-ANP) was characterized using complementary analytical techniques, such as EDX, SEM, XRD and IR spectroscopy. The pre-sowing of soaked seeds of Zea mays in 1.00 µg/mL, 5.00 µg/mL and 10 µg/mL of TU-ANPs yielded growth under 0 mM, 60 mM and 100 mM osmotic stress of NaCl. The results show that Ca and P salt acted as precursors for the synthesis of ANPs at an alkaline pH of 10-11. Thiourea as a source of nitrogen stabilized the ANPs' suspension medium, leading to the synthesis of TU-ANPs. XRD diffraction analysis validated the crystalline nature of TU-ANPs with lattice dimensions of 29 nm, calculated from FWHM using the Sherrer equation. SEM revealed spherical morphology with polydispersion in size distribution. EDS confirmed the presence of Ca and P at a characteristic KeV, whereas IR spectroscopy showed certain stretches of binding functional groups associated with TU-ANPs. Seed priming with TU-ANPs standardized germination indices (T50, MGT, GI and GP) which were significantly declined by NaCl-based osmotic stress. Maximum values for biochemical parameters, such as sugar (39.8 mg/g at 10 µg/mL), protein (139.8 mg/g at 10 µg/mL) and proline (74.1 mg/g at 10 µg/mL) were recorded at different applied doses of TU-ANP. Antioxidant biosystems in the form of EC 1.11.1.6 catalase (11.34 IU/g FW at 10 µg/mL), EC 1.11.1.11 APX (0.95 IU/G FW at 10 µg/mL), EC 1.15.1.1 SOD (1.42 IU/g FW at 5 µg/mL), EC 1.11.1.7 POD (0.43 IU/g FW at 5 µg/mL) were significantly restored under osmotic stress. Moreover, photosynthetic pigments, such as chlorophyll A (2.33 mg/g at 5 µg/mL), chlorophyll B (1.99 mg/g at 5 µg/mL) and carotenoids (2.52 mg/g at 10 µg/mL), were significantly amplified under osmotic stress via the application of TU-ANPs. Hence, the application of TU-ANPs restores the growth performance of plants subjected to induced osmotic stress.

Genome Organization and Comparative Evolutionary Mitochondriomics of Brown Planthopper, Nilaparvata lugens Biotype 4 Using Next Generation Sequencing (NGS).

Nilaparvata lugens is the main rice pest in India. Until now, the Indian N. lugens mitochondrial genome has not been sequenced, which is a very important basis for population genetics and phylogenetic evolution studies. An attempt was made to sequence two examples of the whole mitochondrial genome of N. lugens biotype 4 from the Indian population for the first time. The mitogenomes of N. lugens are 16,072 and 16,081 bp long with 77.50% and 77.45% A + T contents, respectively, for both of the samples. The mitochondrial genome of N. lugens contains 37 genes, including 13 protein-coding genes (PCGs) (cox1-3, atp6, atp8, nad1-6, nad4l, and cob), 22 transfer RNA genes, and two ribosomal RNA (rrnS and rrnL) subunits genes, which are typical of metazoan mitogenomes. However, both samples of N. lugens mitogenome in the present study retained one extra copy of the trnC gene. Additionally, we also found 93 bp lengths for the atp8 gene in both of the samples, which were 60-70 bp less than that of the other sequenced mitogenomes of hemipteran insects. The phylogenetic analysis of the 19 delphacids mitogenome dataset yielded two identical topologies when rooted with Ugyops sp. in one clade, and the remaining species formed another clade with P. maidis and M. muiri being sisters to the remaining species. Further, the genus Nilaparvata formed a separate subclade with the other genera (Sogatella, Laodelphax, Changeondelphax, and Unkanodes) of Delphacidae. Additionally, the relationship among the biotypes of N. lugens was recovered as the present study samples (biotype-4) were separated from the three biotypes reported earlier. The present study provides the reference mitogenome for N. lugens biotype 4 that may be utilized for biotype differentiation and molecular-aspect-based future studies of N. lugens.

The Glycemic Control Potential of Some Amaranthaceae Plants, with Particular Reference to In Vivo Antidiabetic Potential of Agathophora alopecuroides.

Natural products continue to provide inspiring moieties for the treatment of various diseases. In this regard, investigation of wild plants, which have not been previously explored, is a promising strategy for reaching medicinally useful drugs. The present study aims to investigate the antidiabetic potential of nine Amaranthaceae plants: Agathophora alopecuroides, Anabasis lachnantha, Atriplex leucoclada, Cornulaca aucheri, Halothamnus bottae, Halothamnus iraqensis, Salicornia persia, Salsola arabica, and Salsola villosa, growing in the Qassim area, the Kingdom of Saudi Arabia. The antidiabetic activity of the hydroalcoholic extracts was assessed using in vitro testing of α-glucosidase and α-amylase inhibitory effects. Among the nine tested extracts, A. alopecuroides extract (AAE) displayed potent inhibitory activity against α-glucosidase enzyme with IC50 117.9 µg/mL noting better activity than Acarbose (IC50 191.4 µg/mL). Furthermore, AAE displayed the highest α- amylase inhibitory activity among the nine tested extracts, with IC50 90.9 µg/mL. Based upon in vitro testing results, the antidiabetic activity of the two doses (100 and 200 mg/kg) of AAE was studied in normoglycemic and streptozotocin (STZ)-induced diabetic mice. The effects of the extract on body weight, food and water intakes, random blood glucose level (RBGL), fasting blood glucose level (FBGL), insulin, total cholesterol, and triglycerides levels were investigated. Results indicated that oral administration of the two doses of AAE showed a significant dose-dependent increase (p < 0.05) in the body weight and serum insulin level, as well as a significant decrease in food and water intake, RBGL, FBGL, total cholesterol, and triglyceride levels, in STZ-induced diabetic mice, compared with the diabetic control group. Meanwhile, no significant differences of both extract doses were observed in normoglycemic mice when compared with normal control animals. This study revealed a promising antidiabetic activity of the wild plant A. alopecuroides.

Holmium laser enucleation versus bipolar resection in the management of large-volume benign prostatic hyperplasia: A randomized controlled trial.

OBJECTIVES: To compare the mid-term safety and efficacy of holmium laser enucleation of the prostate versus bipolar transurethral resection of the prostate in the management of large-volume benign prostatic hyperplasia. METHODS: From December 2016 to March 2018, patients with benign prostatic hyperplasia (≥80 cc) were randomized (block randomization, computer-generated random list) to holmium laser enucleation of the prostate (57 patients) or bipolar transurethral resection of the prostate (55 patients). Patients were excluded if they had an International Prostate Symptom Score <13, a maximum urinary flow rate >15 mL/s or presence of prostate cancer, bladder stone, urethral stricture, neurogenic bladder, or previous prostate surgery. The primary outcome was hemoglobin loss. The analysis was intention-to-treat. Postoperative findings (36 months) were compared to baseline characteristics. Univariate and logistic regression analyses were performed for risk factors predicting hemoglobin loss or operative time in all patients. RESULTS: There was no significant difference in baseline characteristics between the two groups. Holmium laser enucleation of the prostate was associated with significantly better operative time (P = 0.019), operative efficiency (P < 0.001), hemoglobin loss (P < 0.001), catheterization duration (P < 0.001) and hospital stay (P < 0.001) compared to bipolar transurethral resection of prostate. Both procedures were safe, with no significant difference in total complications (P = 0.128). Blood transfusion (P = 0.026) and capsular perforation (P = 0.239) were reported only in the bipolar transurethral resection of the prostate group. There was no significant difference in rates of urinary tract infections (P = 0.714), urethral strictures (P = 0.359), or transient stress incontinence (P = 0.717). At the last follow-up (3 years), holmium laser enucleation of the prostate was associated with significantly better International Prostate Symptom Scores, prostate-specific antigen levels and maximum urinary flow rates compared to bipolar transurethral resection of the prostate (P < 0.05). In logistic regression analyses, prostate size and bipolar transurethral resection of the prostate were associated with significantly greater hemoglobin loss, whereas prostate size, capsular perforation, and bipolar transurethral resection of the prostate were associated with significantly longer operative time. CONCLUSION: Holmium laser enucleation of the prostate and bipolar transurethral resection of the prostate are effective and safe for the management of moderate-to-severe lower urinary tract symptoms attributable to large-volume benign prostatic hyperplasia (≥80 cc). However, if both techniques are available, holmium laser enucleation of the prostate is preferred due its better efficacy and safety profile.

Antihypertensive medication in frail older adults: A narrative review through a deprescribing lens.

Purpose of review: The management of hypertension in frail older adults remains controversial, as these patients are underrepresented in clinical trials and practice guidelines. Overtreatment may cause harm while undertreatment may lead to greater risk of cardiovascular events. Our research aims to examine this controversy and provide guidance regarding deprescribing decisions in frail older adults. Results: Current evidence suggests that there may be minimal cardiovascular benefit and significant harm of antihypertensive medication in the frail older adult population. A minority of hypertension guidelines provide sufficient recommendations for frail older adults, and there are limited tools available to guide clinical decision-making. Conclusion: Randomized controlled trials and well-designed observational studies are needed to confirm the benefit-to-harm relationship of antihypertensive medication in frail older adults. Decision tools that comprehensively address antihypertensive deprescribing would be advantageous to help clinicians with hypertension management in this population. Clinicians should engage in shared decision-making with the patient and family to ensure that decisions regarding antihypertensive deprescribing best meet the needs of all involved.

Lithographic in-mold patterning for CsPbBr3 nanocrystals distributed Bragg reflector single-mode laser.

Extensive studies on lead halide perovskites have shown that these materials are excellent candidates as gain mediums. Recently, many efforts have been made to incorporate perovskite lasers in integrated optical circuits. Possible solutions would be to utilize standard lithography with an etching/lift-off process or a direct laser etching technique. However, due to the fragile nature of the lead halide perovskites which gives rise to significant material deterioration during the lithography and etching processes, realizing a small-size, low-roughness, and single-mode laser remains a challenge. Here, a lithographic in-mold patterning method realized by nanocrystal concentration control and a multi-step filling-drying process is proposed to demonstrate CsPbBr3 nanocrystals distributed-Bragg-reflector (DBR) waveguide lasers. This method realizes the patterning of the CsPbBr3 nanocrystal laser cavity and DBR grating without lift-off and etching processes, and the smallest fabricated structures are obtained in a few hundred nanometers. The single-mode lasing is demonstrated at room temperature with a threshold of 23.5 µJ cm-2. The smallest full width at half maximum FWHM of the laser output is 0.4 nm. Due to the fabrication process and the DBR laser geometry, the lasers can be fabricated in a compact array, which is important for incorporating perovskite-based lasers in complex optoelectronic circuits.

Bispecific antibody target pair discovery by high-throughput phenotypic screening using in vitro combinatorial Fab libraries.

Bispecific antibodies can uniquely influence cellular responses, but selecting target combinations for optimal functional activity remains challenging. Here we describe a high-throughput, combinatorial, phenotypic screening approach using a new bispecific antibody target discovery format, allowing screening of hundreds of target combinations. Simple in vitro mixing of Fab-fusion proteins from a diverse library enables the generation of thousands of screen-ready bispecific antibodies for high-throughput, biologically relevant assays. We identified an obligate bispecific co-targeting CD79a/b and CD22 as a potent inhibitor of human B cell activation from a short-term flow cytometry signaling assay. A long-term, high-content imaging assay identified anti-integrin bispecific inhibitors of human cell matrix accumulation targeting integrins ß1 and ß6 or αV and ß1. In all cases, functional activity was conserved from the bispecific screening format to a therapeutically relevant format. We also introduce a broader type of mechanistic screen whereby functional modulation of different cell subsets in peripheral blood mononuclear cells was evaluated simultaneously. We identified bispecific antibodies capable of activating different T cell subsets of potential interest for applications in oncology or infectious disease, as well as bispecifics abrogating T cell activity of potential interest to autoimmune or inflammatory disease. The bispecific target pair discovery technology described herein offers access to new target biology and unique bispecific therapeutic opportunities in diverse disease indications.

Association of Anti-TNF Therapy With Increased Risk of Acute Cholangitis in Patients With Primary Sclerosing Cholangitis.

BACKGROUND: Patients with primary sclerosing cholangitis (PSC) are at increased risk of developing acute cholangitis. The majority of patients with PSC have comorbid inflammatory bowel disease, and many take immunosuppressive medications. The epidemiological risks for the development of acute cholangitis in patients with PSC, including the impact of immunosuppressive therapy, are unknown. METHODS: We conducted a 2-center, retrospective cohort study using data from 228 patients at Stanford University Medical Center and Santa Clara Valley Medical Center (CA), a county health care system. Patient demographics, medications, PSC disease severity, and inflammatory bowel disease status were extracted. Using stepwise variable selection, we included demographic and covariate predictors in the multiple logistic regression model assessing risk factors for cholangitis. Time-to-event analysis was performed to evaluate specific immunosuppressive medications and development of cholangitis. RESULTS: Thirty-one percent of patients had at least 1 episode of acute cholangitis (n = 72). Anti-tumor necrosis factor (TNF) therapy was associated with increased odds of acute cholangitis (odds ratio, 7.29; 95% confidence interval, 2.63-12.43), but immunomodulator use was protective against acute cholangitis (odds ratio, 0.23; 95% confidence interval, 0.05-0.76). Anti-TNF therapy was associated with decreased time-to-cholangitis, with a median time of 28.4 months; in contrast, only 11.1% of patients who were prescribed immunomodulators developed cholangitis over the same time period (P < 0.001). CONCLUSIONS: Our observations suggest that classes of immunosuppressive medications differentially modify the odds of acute cholangitis. Biologic therapy, ie, anti-TNF therapy, was shown to have significantly higher odds for patients developing acute cholangitis whereas immunomodulator therapy was shown to have a potential protective effect. These findings may help guide physicians in decision-making for determining appropriate immunosuppressive therapy.

Efficiency of vanillin in impeding metabolic adaptability and virulence of Candida albicans by inhibiting glyoxylate cycle, morphogenesis, and biofilm formation.

BACKGROUND AND PURPOSE: Candida albicans is the fourth most common cause of nosocomial fungal infections across the world. The current drug regimens are suffering from such drawbacks as drug resistance, toxicity, and costliness; accordingly, they highlight the need for the discovery of novel drug agents. The metabolic adaptability under low-carbon conditions and expression of functional virulence traits mark the success of pathogens to cause infection. The metabolic pathways, such as glyoxylate cycle (GC), enable C. albicans to survive under glucose-deficient conditions prevalent in the hostile niche. Therefore, the key enzymes, namely isocitrate lyase (ICL) and malate synthase (MLS), represent attractive agents against C. albicans. Similarly, virulence traits, such as morphogenesis and biofilm formation, are the crucial determinants of C. albicans pathogenicity. Regarding this, the present study was conducted to uncover the role of vanillin (Van), a natural food flavoring agent, in inhibiting GC, yeast-to-hyphal transition, and biofilm formation in human fungal pathogen C. albicans. MATERIALS AND METHODS: For the determination of hypersensitivity under low-glucose conditions, phenotypic susceptibility assay was utilized. In addition, enzyme activities were estimated based on crude extracts while in-silico binding was confirmed by molecular docking. The assessment of morphogenesis was accomplished using hyphal-inducing media, and biofilm formation was estimated using calcofluor staining, MTT assay, and biomass measurement. Additionally, the in vivo efficacy of Van was demonstrated using Caenorhabditis elegans nematode model. RESULTS: Based on the results, Van was found to be a potent GC inhibitor that phenocopied ICL1 deletion mutant and displayed hypersensitivity under low-carbon conditions. Accordingly, Van facilitated the inhibition of ICL and MLS activities in vitro. Molecular docking analyses revealed the in-silico binding affinity of Van with Icl1p and Mls1p. Those analyses were also confirmative of the binding of Van to the active sites of both proteins with better binding energy in comparison to their known inhibitors. Furthermore, Van led to the attenuation of such virulence traits as morphogenesis, biofilm formation, and cell adherence. Finally, the antifungal efficacy of Van was demonstrated by the enhanced survival of C. elegans with Candida infection. The results also confirmed negligible hemolytic activity on erythrocytes. CONCLUSION: As the findings of the present study indicated, Van is a persuasive natural compound that warrants further attention to exploit its anticandidal potential.