Trial of Early Minimally Invasive Removal of Intracerebral Hemorrhage.

BACKGROUND: Trials of surgical evacuation of supratentorial intracerebral hemorrhages have generally shown no functional benefit. Whether early minimally invasive surgical removal would result in better outcomes than medical management is not known. METHODS: In this multicenter, randomized trial involving patients with an acute intracerebral hemorrhage, we assessed surgical removal of the hematoma as compared with medical management. Patients who had a lobar or anterior basal ganglia hemorrhage with a hematoma volume of 30 to 80 ml were assigned, in a 1:1 ratio, within 24 hours after the time that they were last known to be well, to minimally invasive surgical removal of the hematoma plus guideline-based medical management (surgery group) or to guideline-based medical management alone (control group). The primary efficacy end point was the mean score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes, according to patients' assessment) at 180 days, with a prespecified threshold for posterior probability of superiority of 0.975 or higher. The trial included rules for adaptation of enrollment criteria on the basis of hemorrhage location. A primary safety end point was death within 30 days after enrollment. RESULTS: A total of 300 patients were enrolled, of whom 30.7% had anterior basal ganglia hemorrhages and 69.3% had lobar hemorrhages. After 175 patients had been enrolled, an adaptation rule was triggered, and only persons with lobar hemorrhages were enrolled. The mean score on the utility-weighted modified Rankin scale at 180 days was 0.458 in the surgery group and 0.374 in the control group (difference, 0.084; 95% Bayesian credible interval, 0.005 to 0.163; posterior probability of superiority of surgery, 0.981). The mean between-group difference was 0.127 (95% Bayesian credible interval, 0.035 to 0.219) among patients with lobar hemorrhages and -0.013 (95% Bayesian credible interval, -0.147 to 0.116) among those with anterior basal ganglia hemorrhages. The percentage of patients who had died by 30 days was 9.3% in the surgery group and 18.0% in the control group. Five patients (3.3%) in the surgery group had postoperative rebleeding and neurologic deterioration. CONCLUSIONS: Among patients in whom surgery could be performed within 24 hours after an acute intracerebral hemorrhage, minimally invasive hematoma evacuation resulted in better functional outcomes at 180 days than those with guideline-based medical management. The effect of surgery appeared to be attributable to intervention for lobar hemorrhages. (Funded by Nico; ENRICH ClinicalTrials.gov number, NCT02880878.).

Engineered Artesunate-Naphthalimide Hybrid Dual Drug for Synergistic Multimodal Therapy against Experimental Murine Lymphoma.

Lymphoma can effectively be treated with a chemotherapy regimen that is associated with adverse side effects due to increasing drug resistance, so there is an emergent need for alternative small-molecule inhibitors to overcome the resistance that occurs in lymphoma management and overall increase the prognosis rate. A new series of substituted naphthalimide moieties conjugated via ester and amide linkages with artesunate were designed, synthesized, and characterized. In addition to the conjugates, to further achieve a theranostic molecule, FITC was incorporated via a multistep synthesis process. DNA binding studies of these selected derivatives by ultraviolet-visible (UV-vis), fluorescence spectroscopy, intercalating dye (EtBr, acridine orange)-DNA competitive assay, and minor groove binding dye Hoechst 33342-DNA competitive assay suggested that the synthesized novel molecules intercalated between the two strands of DNA due to its naphthalimide moiety and its counterpart artesunate binds with the minor groove of DNA. Napthalimide-artesunate conjugates inhibit the growth of lymphoma and induce apoptosis, including ready incorporation and reduction in cell viability. The remodeled drug has a significant tumoricidal effect against solid DL tumors developed in BALB/c mice in a dose-dependent manner. The novel drug appears to inhibit metastasis and increase the survival of the treated animals compared with untreated littermates.

Physiological and molecular insights into the allelopathic effects on agroecosystems under changing environmental conditions.

Allelopathy is a natural phenomenon of competing and interfering with other plants or microbial growth by synthesizing and releasing the bioactive compounds of plant or microbial origin known as allelochemicals. This is a sub-discipline of chemical ecology concerned with the effects of bioactive compounds produced by plants or microorganisms on the growth, development and distribution of other plants and microorganisms in natural communities or agricultural systems. Allelochemicals have a direct or indirect harmful effect on one plant by others, especially on the development, survivability, growth, and reproduction of species through the production of chemical inhibitors released into the environment. Cultivation systems that take advantage of allelopathic plants' stimulatory/inhibitory effects on plant growth and development while avoiding allelopathic autotoxicity is critical for long-term agricultural development. Allelopathy is one element that defines plant relationships and is involved in weed management, crop protection, and microbial contact. Besides, the allelopathic phenomenon has also been reported in the forest ecosystem; however, its presence depends on the forest type and the surrounding environment. In the present article, major aspects addressed are (1) literature review on the impacts of allelopathy in agroecosystems and underpinning the research gaps, (2) chemical, physiological, and ecological mechanisms of allelopathy, (3) genetic manipulations, plant defense, economic benefits, fate, prospects and challenges of allelopathy. The literature search and consolidation efforts in this article shall pave the way for future research on the potential application of allelopathic interactions across various ecosystems.

Gating effect for gas adsorption in microporous materials-mechanisms and applications.

In the past two decades, various microporous materials have been developed as useful adsorbents for gas adsorption for a wide range of industries. Considerable efforts have been made to regulate the pore accessibility in microporous materials for the manipulation of guest molecules' admission and release. It has long been known that some microporous adsorbents suddenly become highly accessible to guest molecules at specific conditions, e.g., above a threshold pressure or temperature. This anomalous adsorption behavior results from a gating effect, where a structural variation of the adsorbent leads to an abrupt change in the gas admission. This review summarizes the mechanisms of the gating effect, which can be a result of the deformation of the framework (e.g., expansion, contraction, reorientation, and sliding of the unit cells), the vibration of the pore-keeping groups (e.g., rotation, swing, and collapse of organic linkers), and the oscillation of the pore-keeping ions (e.g. cesium, potassium, etc.). These structural variations are induced either by the host-guest interaction or by an external stimulus, such as temperature or light, and account for the gating effect at a threshold value of the stimulus. Emphasis is given to the temperature-regulated gating effect, where the critical admission temperature is dictated by the combined effect of the gate opening and thermodynamic factors and plays a key role in regulating guest admission. Molecular simulations can improve our understanding of the gate opening/closing transitions at the atomic scale and enable the construction of quantitative models to describe the gated adsorption behaviour at the macroscale level. The gating effect in porous materials has been widely applied in highly selective gas separation and offers great potential for gas storage and sensing.

γc cytokine-aided crosstalk between dendritic cells and natural killer cells together with doxorubicin induces a healer response in experimental lymphoma by downregulating FOXP3 and programmed cell death protein 1.

BACKGROUND AIMS: The stimulatory natural killer-dendritic cell axis in the tumor microenvironment could play a critical role in stimulating cytotoxic T cells and driving immune responses against cancer. METHODS: We established a novel treatment protocol by adroitly combining chemotherapy with doxorubicin and immunotherapy with dendritic cells and natural killer cells against a highly aggressive and malignant lymphoma called Dalton's lymphoma. RESULTS: Our data suggest that binary application of adoptive cell therapy and chemotherapy nearly cures (95%) early-stage experimental lymphoma. In the case of mid-stage cancer, the success rate was significantly lower but still impressive (75%). Our results demonstrated that the application of combination therapy in early-stage cancer significantly reduced the tumor volume and extended the lifespan of the experimental animal in addition to reinvigorating the immune system, including restoring the effector functions of dendritic cells and natural killer cells. The novel protocol limits the metastasis of tumor cells in vascularized organs and rearms the adaptive immune response mediated by dendritic cells and CD4+ and CD8+ T cells. CONCLUSIONS: Combination therapy in the early stage alters the cytokine profile, increases interferon-γ and tumor necrosis factor-α in the serum of treated animals and downregulates programmed cell death protein 1 expression in CD8+ T cells. Thus, cooperative and cognitive interactions between dendritic cells and natural killer cells in addition to therapy with doxorubicin promote the immune response and tumoricidal activities against lymphoma.

Nitrogen Rejection from Methane via a "Trapdoor" K-ZSM-25 Zeolite.

Nitrogen (N2) rejection from methane (CH4) is the most challenging step in natural gas processing because of the close similarity of their physical-chemical properties. For decades, efforts to find a functioning material that can selectively discriminate N2 had little outcome. Here, we report a molecular trapdoor zeolite K-ZSM-25 that has the largest unit cell among all zeolites, with the ability to capture N2 in favor of CH4 with a selectivity as high as 34. This zeolite was found to show a temperature-regulated gas adsorption wherein gas molecules' accessibility to the internal pores of the crystal is determined by the effect of the gas-cation interaction on the thermal oscillation of the "door-keeping" cation. N2 and CH4 molecules were differentiated by different admission-trigger temperatures. A mild working temperature range of 240-300 K was determined wherein N2 gas molecules were able to access the internal pores of K-ZSM-25 while CH4 was rejected. As confirmed by experimental, molecular dynamic, and ab initio density functional theory studies, the outstanding N2/CH4 selectivity is achieved within a specific temperature range where the thermal oscillation of door-blocking K+ provides enough space only for the relatively smaller molecule (N2) to diffuse into and through the zeolite supercages. Such temperature-regulated adsorption of the K-ZSM-25 trapdoor zeolite opens up a new approach for rejecting N2 from CH4 in the gas industry without deploying energy-intensive cryogenic distillation around 100 K.

Targeting PD-1 in CD8+ T Cells with a Biomimetic Bilirubin-5-fluoro-2-deoxyuridine-Bovine Serum Albumin Nanoconstruct for Effective Chemotherapy against Experimental Lymphoma.

We fabricated bilirubin-bovine serum albumin (BR-BSA) nanocomplexes as candidates for the delivery of 5-fluoro-2-deoxyuridine (5FUdr) against experimental murine lymphoma. BR was attached to 5FUdr via acid-labile ester bonds mimicking small-molecule drug conjugates. The construct was self-assembled with BSA through strong noncovalent interactions with high drug occupancy in the core and labeled with folic acid (FA) to target cancer cells. The BR-5FUdr-BSA-FA nanoconstruct exhibits excellent biocompatibility, prevents nephrotoxicity, and is tolerated by red blood cells and mononuclear cells. The construct also showed increased accumulation in lymph nodes and tumor cells. BR-5FUdr-BSA-FA caused prolonged growth inhibition and apoptosis, enhanced mitochondrial reactive oxygen species generation, and minimized the viability of parental and doxorubicin-resistant Dalton's lymphoma cells. Treatment of tumor-bearing mice with BR-5FUdr-BSA-FA significantly increased the life span of the animals, improved their histopathological parameters, and downregulated PD-1 expression, suggesting the potential of the construct for 5FUdr delivery to treat lymphoma.

Phytostabilization of coal mine overburden waste, exploiting the phytoremedial efficacy of lemongrass under varying level of cow dung manure.

A pot study was performed to assess the phytoremedial potential of Cymbopogon citratus (D.C.) Staf. for reclamation of coal mine overburden dump wastes, emphasizing the outcome of amendment practices using cow dung manure (CM) and garden soil mixtures on the revegetation of over-burden wastes (OB). Wastes amendment with cow dung manure and garden soil resulted in a significant increase in soil health and nutrient status along with an increment in the phytoavailability of Zn and Cu which are usually considered as micronutrients, essential for plant growth. A significant increment in the total biomass of lemongrass by 38.6% under CM20 (OB: CM 80:20) was observed along with improved growth parameters under amended treatments as compared to OB (100% waste). Furthermore, the proportionate increases in the assimilative rate, water use efficiency, and chlorophyll fluorescence have been observed with the manure application rates. Lemongrass emerged out to be an efficient metal-tolerant herb species owing to its high metal-tolerance index (>100%). Additionally, lemongrass efficiently phytostablized Pb and Ni in the roots. Based on the strong plant performances, the present study highly encourages the cultivation of lemongrass in coal mining dumpsites for phytostabilization coupled with cow-dung manure application (20% w/w).

Leishmanicidal Activity of an In Silico-Screened Novel Inhibitor against Ascorbate Peroxidase of Leishmania donovani.

Peroxidases are a heterogeneous family of enzymes that have diverse biological functions. Ascorbate peroxidase is a redox enzyme that is reduced by trypanothione, which plays a central role in the redox defense system of Leishmania In view of developing new and novel therapeutics, we performed in silico studies in order to search for a ligand library and identify new drug candidates and their physiological roles against promastigotes and intracellular amastigotes of Leishmania donovani Our results demonstrated that the selected inhibitor ZINC96021026 has significant antileishmanial effect and effectively killed both free and intracellular forms of the parasite. ZINC96021026 was found to be identical to ML-240, a selective inhibitor of valosin-containing protein (VCP), or p97, a member of the AAA-ATPase protein family which was derived from the scaffold of N2,N4-dibenzylquinazoline-2,4-diamine (DBeQ), targeting the D2-ATPase domain of the enzyme. ZINC96021026 (ML-240) thus has a broad range of cellular functions, thought to be derived from its ability to unfold proteins or disassemble protein complexes, besides inhibiting the ascorbate peroxidase activity. ML-240 may inhibit the parasite's ascorbate peroxidase, leading to extensive apoptosis and inducing generation of reactive oxygen species. Taken together, our results demonstrated that ML-240 could be an attractive therapeutic option for treatment against leishmaniasis.

Identification & characterization of leucine-rich repeat kinase 2 & parkin RBR E3 ubiquitin protein ligase variants in patients with Parkinson's disease.

BACKGROUND & OBJECTIVES: Parkinson's disease (PD) is a motor disorder that affects movement. More than 24 loci and 28 associated genes have been identified to be associated with this disease. The present study accounts for the contribution of two candidates, leucine-rich repeat kinase 2 ( LRRK2) and parkin RBR E3 ubiquitin protein ligase ( PRKN) in the PD patients, and their characterization in silico and in vitro. METHODS: A total of 145 sporadic PD cases and 120 ethnically matched healthy controls were enrolled with their informed consent. Mutation screening was performed by direct DNA sequencing of the targeted exons of LRRK2 and all exons flanking introns of PRKN. The effect of the pathogenic PRKN variants on a drug (MG-132) induced loss of mitochondrial membrane potential (△ΨM) was measured by a fluorescent dye tetramethylrhodamine methyl ester (TMRM). RESULTS: Twelve and 20 genetic variants were identified in LRRK2 and PRKN, respectively. Interestingly, five out of seven exonic LRRK2 variants were synonymous. Further assessment in controls confirmed the rarity of two such p.Y1527 and p.V1615. Among the pathogenic missense variations (as predicted in silico) in PRKN, two were selected (p.R42H and p.A82E) for their functional study in vitro, which revealed the reduced fluorescence intensity of TMRM as compared to wild type, in case of p.R42H but not the other. INTERPRETATION & CONCLUSIONS: About 6.2 per cent of the cases (9/145) in the studied patient cohort were found to carry pathogenic (as predicted in silico) missense variations in PRKN in heterozygous condition but not in case of LRRK2 which was rare. The presence of two rare synonymous variants of LRRK2 (p.Y1527 and p.V1615) may support the phenomenon of codon bias. Functional characterization of selected PRKN variations revealed p.R42H to cause disruption of mitochondrial membrane potential (△ΨM) rendering cells more susceptible to cellular stress.

Doxorubicin loaded pH responsive biodegradable ABA-type Amphiphilic PEG-b-aliphatic Polyketal-b-PEG block copolymer for therapy against aggressive murine lymphoma.

A novel ABA-type polyethylene glycol (PEG)-b-polyketal (PK)-b-PEG block copolymer was synthesized via click reactions between the monoazido-monomethoxy-PEG and dialkyne terminated aliphatic polyketal with no carboxylic/amide linkages. Formation of the novel block copolymer was confirmed by 1H NMR, GPC, TGA, and DSC studies. The formed copolymer has shown faster degradation at acidic pH. Self-assembly of this block copolymer (average size 6.2 nm) was assessed by fluorescence study using pyrene as a probe. Doxorubicin loaded block copolymeric micelles (69.9 nm) have shown pH dependent elevated drug release at pH 6.4, indicating its potential as a pH responsive nano-carrier for anticancer therapy. The nano-sized copolymer demonstrated tumoricidal activities against the lymphoma of murine and human origin with significant levels of growth inhibition and apoptosis. Therapy with doxorubicin loaded copolymer reduced the tumor size and augmented the life span of the tumor bearing animals with improved histopathological parameters, compared with the untreated control.

Proximate composition and element contents of selected species of Ganoderma with reference to dietary intakes.

Ganoderma is a wood-degrading mushroom that is treasured as a functional food since primitive times. Monitoring of macronutrient and element levels in mushrooms collected from the natural environment provides basic information in terms of safety, regulation, and nutrition. A comparative study was developed on the proximate and element contents of Ganoderma applanatum, G. brownii, G. lucidum, and G. philippii collected from different zones of the natural forests in Uttarakhand, India. These mushrooms revealed high amounts of proteins (9.29-12.4%) and carbohydrates (75.5-80.3%) and low contents of fats (1.62-2.87%), but ash (6.14-8.32%) and fibre (4.92-8.07%) were available in significant amounts. Element concentrations were determined by wavelength dispersive X-ray fluorescence (WDXRF) spectrometry. Calcium (5400-19,250 mg/kg) and potassium (2602-5601 mg/kg) were the predominant elements in mushrooms. The mushroom samples provided significant percentage contribution to reference recommended dietary intakes (RDIs) of essential elements such as calcium (27.0-96.3%), copper (58.2-95.8%), and manganese (37.3-62.3%), for adult males and females; and iron (35.3-97.1% for males and 28.6-78.6% for females), magnesium (7.06-11.5% for males and 7.74-12.6% for females), and zinc (6.35-19.8% for males and 7.65-23.7% for females). The studied mushrooms have no health risks as toxic metals such as aluminium and lead were detected below the legislated respective provisional tolerable intake values. Nutritional quality index (NQI) values revealed that mushrooms are densely rich in calcium, copper, iron, magnesium, manganese, and zinc.

Functioning of Mycobacterial Heat Shock Repressors Requires the Master Virulence Regulator PhoP.

A hallmark feature of Mycobacterium tuberculosis pathogenesis lies in the ability of the pathogen to survive within macrophages under a stressful environment. Thus, coordinated regulation of stress proteins is critically important for an effective adaptive response of M. tuberculosis, the failure of which results in elevated immune recognition of the tubercle bacilli with reduced survival during chronic infections. Here, we show that virulence regulator PhoP impacts the global regulation of heat shock proteins, which protect M. tuberculosis against stress generated by macrophages during infection. Our results identify that in addition to classical DNA-protein interactions, newly discovered protein-protein interactions control complex mechanisms of expression of heat shock proteins, an essential pathogenic determinant of M. tuberculosis While the C-terminal domain of PhoP binds to its target promoters, the N-terminal domain of the regulator interacts with the C-terminal end of the heat shock repressors. Remarkably, our findings delineate a regulatory pathway which involves three major transcription factors, PhoP, HspR, and HrcA, that control in vivo recruitment of the regulators within the target genes and regulate stress-specific expression of heat shock proteins via protein-protein interactions. The results have implications on the mechanism of regulation of PhoP-dependent stress response in M. tuberculosisIMPORTANCE The regulation of heat shock proteins which protect M. tuberculosis against stress generated by macrophages during infection is poorly understood. In this study, we show that PhoP, a virulence regulator of the tubercle bacilli, controls heat shock-responsive genes, an essential pathogenic determinant of M. tuberculosis Our results unravel that in addition to classical DNA-protein interactions, complex mechanisms of regulation of heat shock-responsive genes occur through multiple protein-protein interactions. Together, these findings delineate a fundamental regulatory pathway where transcription factors PhoP, HspR, and HrcA interact with each other to control stress-specific expression of heat shock proteins.

Electroconvulsive Therapy for Super Refractory Status Epilepticus.

OBJECTIVES: Super refractory status epilepticus (SRSE) is a stage beyond refractory status that requires general anesthesia as management. Electroconvulsive therapy (ECT) is recommended only as a potential treatment option beyond general anesthesia and after all other options have been exhausted. Its effect on aborting status has been minimally researched. We present the largest case series to our knowledge exploring the effect of ECT on SRSE. METHODS: Eight adults hospitalized for SRSE received ECT in an attempt to abort status after other treatment modalities were exhausted. Electroconvulsive therapy consisted of a 504-mC (≈99.4 J) stimulus delivered bifrontotemporally with a constant 0.5-millisecond pulse width. Seizure activity during ECT was monitored visually and correlated to the single-channel recording provided by the apparatus. RESULTS: There was neurotelemetry or clinical evidence of improvement within 24 hours after the full course of ECT treatment in 5 (63%) of the 8 cases. Cases that improved were given an average of 7.8 total ECT stimulations, eliciting an average of 4.2 total seizures. CONCLUSIONS: Although it is difficult to determine the exact role of ECT in the improvement of 63% of our cases, we present a series of patients for whom pharmacotherapy, ketogenic diet, and general anesthesia otherwise did not produce an appreciable effect on status prior to implementation of ECT. These findings suggest that cases of SRSE may benefit from ECT administration.

Tuberculosis Penis with 'Watering Can Penis' Appearance: Report of a Rare Case with Retrograde Urethrography and Voiding Cystourethrography Findings.

BACKGROUND: A 'watering can penis' secondary to penile tuberculosis is an extremely rare clinical entity. Retrograde Urethrography - Voiding Cystourethrography evaluation of the urethra and the urinary bladder plays a very important role in the diagnostics as well as further management of the urethral abnormalities. To the best of our knowledge, this is only the second case in literature where a 'watering can penis' was noted secondary to penile TB. This is also the first documented case of 'watering can penis' as a consequence of venereal transmission of TB. CASE REPORT: A 50-year-old male presented with multiple discharging sinuses along the penis. RGU revealed multiple, contrast-filled, narrow, irregular, fistulous tracts arising from the pendulous part of the anterior urethra. This distal segment of the pendulous part of the anterior urethra also showed significant distortion and irregular, beaded narrowing. VCUG showed a markedly-contracted and small-capacity urinary bladder with a thickened, irregular and edematous wall with multiple hypertrophied trabeculae along its walls. The patient was administered anti-tubercular treatment. At the end of this treatment regimen, a repeat RGU-VCUG will be performed and decision regarding urethroplasty and further management will be planned depending upon the presence of any remaining fistulas or strictures involving the urethra. CONCLUSIONS: 'Watering can penis' as a result of penile TB is a very rare clinical entity. The differential diagnoses of a 'watering can penis' should be kept in mind in the evaluation of these patients. RGU and VCUG evaluation is an important conventional imaging modality used in the evaluation of urethral strictures and fistulas in case of 'watering can penis'.

A transcriptional co-repressor regulatory circuit controlling the heat-shock response of Mycobacterium tuberculosis.

The co-ordinated regulation of heat shock proteins is critically important for the stress response of M. tuberculosis, failure of which results in enhanced immune recognition of the tubercle bacilli with reduced survival during chronic infections. In this study, we show that PhoP regulates the transcription of α-crystallin 2 (acr2), expression of which increases more than any other gene of M. tuberculosis during heat-shock or following macrophage infection. We also show that regulation of acr2 by PhoP is attributable to direct regulator-promoter interactions at specific sites proximal to a sequence motif comprising the target site of another virulence factor, HspR. While both these regulators, on their own, are capable of influencing acr2 expression, remarkably our results show that the two virulence regulators PhoP and HspR interact with each other to influence their in vivo recruitment at the acr2 regulatory region, and in turn, contribute to stress-specific regulation of acr2 expression. We propose a model to suggest how protein-protein interactions between PhoP and HspR influence the regulation of α-crystallin 2, an essential pathogenic determinant of M. tuberculosis.

Aluminum phosphide poisoning: Possible role of supportive measures in the absence of specific antidote.

Aluminum phosphide (ALP) poisoning is one of the major causes of suicidal deaths. Toxicity by ALP is caused by the liberation of phosphine gas, which rapidly causes cell hypoxia due to inhibition of oxidative phosphorylation, leading to circulatory failure. Treatment of ALP toxicity is mainly supportive as there is no specific antidote. We recently managed 7 cases of ALP poisoning with severe hemodynamic effects. Patients were treated with supportive measures including gastric lavage with diluted potassium permanganate, coconut oil and sodium-bicarbonate first person account should be avoided in a scientific paper. Intravenous magnesium sulfate, proper hemodynamic monitoring and vasopressors. Four out of 7 survived thus suggesting a role of such supportive measures in the absence of specific antidote for ALP poisoning.

Action and target sites of nitric oxide in chloroplasts.

Nitric oxide (NO) is an important signalling molecule in plants under physiological and stress conditions. Here we review the influence of NO on chloroplasts which can be directly induced by interaction with the photosynthetic apparatus by influencing photophosphorylation, electron transport activity and oxido-reduction state of the Mn clusters of the oxygen-evolving complex or by changes in gene expression. The influence of NO-induced changes in the photosynthetic apparatus on its functions and sensitivity to stress factors are discussed.

Adsorption of CO2, N2, and CH4 in Cs-exchanged chabazite: a combination of van der Waals density functional theory calculations and experiment study.

The crucial role of dispersion force in correctly describing the adsorption of some typical small-size gas molecules (e.g., CO2, N2, and CH4) in ion-exchanged chabazites has been investigated at different levels of theory, including the standard density functional theory calculation using the Perdew, Burke, and Ernzerhof (PBE) exchange-correlation functional and van der Waals density functional theory (vdWDFT) calculations using different exchange-correlation models - vdW_DF2, optB86b, optB88, and optPBE. Our results show that the usage of different vdWDFT functionals does not significantly change the adsorption configuration or the profile of static charge rearrangement of the gas-chabazite complexes, in comparison with the results obtained using the PBE. The calculated values of adsorption enthalpy using different functionals are compared with our experimental results. We conclude that the incorporation of dispersion interaction is imperative to correctly predict the trend of adsorption enthalpy values, in terms of different gas molecules and Cs(+) cation densities in the adsorbents, even though the absolute values of adsorption enthalpy are overestimated by approximate 10 kJ/mol compared with experiments.

Evaluation of regulatory T-cells in cancer immunotherapy: therapeutic relevance of immune checkpoint inhibition.

The evolution of the complex immune system is equipped to defend against perilous intruders and concurrently negatively regulate the deleterious effect of immune-mediated inflammation caused by self and nonself antigens. Regulatory T-cells (Tregs) are specialized cells that minimize immune-mediated inflammation, but in malignancies, this feature has been exploited toward cancer progression by keeping the antitumor immune response in check. The modulation of Treg cell infiltration and their induction in the TME (tumor microenvironment) alongside associated inhibitory molecules, both soluble or membranes tethered in the TME, have proven clinically beneficial in boosting the tumoricidal activity of the immune system. Moreover, Treg-associated immune checkpoints pose a greater obstruction in cancer immunotherapy. Inhibiting or blocking active immune checkpoint signaling in combination with other therapies has proven clinically beneficial. This review summarizes the ontogeny of Treg cells and their migration, stability, and function in the TME. We also elucidate the Treg-associated checkpoint moieties that impede effective antitumor activity and harness these molecules for effective and targeted immunotherapy against cancer nuisance.