The translocation of a chloride channel from the Golgi to the plasma membrane helps plants adapt to salt stress.

A key mechanism employed by plants to adapt to salinity stress involves maintaining ion homeostasis via the actions of ion transporters. While the function of cation transporters in maintaining ion homeostasis in plants has been extensively studied, little is known about the roles of their anion counterparts in this process. Here, we describe a mechanism of salt adaptation in plants. We characterized the chloride channel (CLC) gene AtCLCf, whose expression is regulated by WRKY transcription factor under salt stress in Arabidopsis thaliana. Loss-of-function atclcf seedlings show increased sensitivity to salt, whereas AtCLCf overexpression confers enhanced resistance to salt stress. Salt stress induces the translocation of GFP-AtCLCf fusion protein to the plasma membrane (PM). Blocking AtCLCf translocation using the exocytosis inhibitor brefeldin-A or mutating the small GTPase gene AtRABA1b/BEX5 (RAS GENES FROM RAT BRAINA1b homolog) increases salt sensitivity in plants. Electrophysiology and liposome-based assays confirm the Cl-/H+ antiport function of AtCLCf. Therefore, we have uncovered a mechanism of plant adaptation to salt stress involving the NaCl-induced translocation of AtCLCf to the PM, thus facilitating Cl- removal at the roots, and increasing the plant's salinity tolerance.

Chronic arsenic poisoning: A sinister cause of peripheral neuropathy in a young couple.

ABSTRACT: Arsenic compounds are colorless and odorless and toxicity can occur either acutely following ingestion of arsenicals with gastrointestinal disturbances or due to chronic exposure usually presenting with dermatologic lesions and peripheral neuropathy. We report a young couple who presented with signs and symptoms of painful sensorimotor peripheral neuropathy in a typical "stocking and glove" pattern. They had raised urinary arsenic levels with normal blood levels and thus, a diagnosis of chronic arsenic poisoning due to contaminated water intake was made after detecting elevated arsenic levels in their home water supply. Both patients underwent chelation therapy with dimercaprol for 14 days and reported subjective and objective improvement in symptoms with the reduction in urinary arsenic levels at the end of therapy.

Arabidopsis class II TPS controls root development and confers salt stress tolerance through enhanced hydrophobic barrier deposition.

KEY MESSAGE: The mechanism of conferring salt tolerance by AtTPS9 involves enhanced deposition of suberin lamellae in the Arabidopsis root endodermis, resulting in reduction of Na+ transported to the leaves. Members of the class I trehalose-6-phosphate synthase (TPS) enzymes are known to play an important role in plant growth and development in Arabidopsis. However, class II TPSs and their functions in salinity stress tolerance are not well studied. We characterized the function of a class II TPS gene, AtTPS9, to understand its role in salt stress response and root development in Arabidopsis. The attps9 mutant exhibited significant reduction of soluble sugar levels in the leaves and formation of suberin lamellae (SL) in the endodermis of roots compared to the wild type (WT). The reduction in SL deposition (hydrophobic barriers) leads to increased apoplastic xylem loading, resulting in enhanced Na+ content in the plants, which explains salt sensitivity of the mutant plants. Conversely, AtTPS9 overexpression lines exhibited increased SL deposition in the root endodermis along with increased salt tolerance, showing that regulation of SL deposition is one of the mechanisms of action of AtTPS9 in conferring salt tolerance to Arabidopsis plants. Our data showed that besides salt tolerance, AtTPS9 also regulates seed germination and root development. qRT-PCR analyses showed significant downregulation of selected SNF1-RELATED PROTEIN KINASE2 genes (SnRK2s) and ABA-responsive genes in the mutant, suggesting that AtTPS9 may regulate the ABA-signaling intermediates as part of the mechanism conferring salinity tolerance.

CLU (clusterin) and PPARGC1A/PGC1α coordinately control mitophagy and mitochondrial biogenesis for oral cancer cell survival.

Mitophagy involves the selective elimination of defective mitochondria during chemotherapeutic stress to maintain mitochondrial homeostasis and sustain cancer growth. Here, we showed that CLU (clusterin) is localized to mitochondria to induce mitophagy controlling mitochondrial damage in oral cancer cells. Moreover, overexpression and knockdown of CLU establish its mitophagy-specific role, where CLU acts as an adaptor protein that coordinately interacts with BAX and LC3 recruiting autophagic machinery around damaged mitochondria in response to cisplatin treatment. Interestingly, CLU triggers class III phosphatidylinositol 3-kinase (PtdIns3K) activity around damaged mitochondria, and inhibition of mitophagic flux causes the accumulation of excessive mitophagosomes resulting in reactive oxygen species (ROS)-dependent apoptosis during cisplatin treatment in oral cancer cells. In parallel, we determined that PPARGC1A/PGC1α (PPARG coactivator 1 alpha) activates mitochondrial biogenesis during CLU-induced mitophagy to maintain the mitochondrial pool. Intriguingly, PPARGC1A inhibition through small interfering RNA (siPPARGC1A) and pharmacological inhibitor (SR-18292) treatment counteracts CLU-dependent cytoprotection leading to mitophagy-associated cell death. Furthermore, co-treatment of SR-18292 with cisplatin synergistically suppresses tumor growth in oral cancer xenograft models. In conclusion, CLU and PPARGC1A are essential for sustained cancer cell growth by activating mitophagy and mitochondrial biogenesis, respectively, and their inhibition could provide better therapeutic benefits against oral cancer.

Concomitant interventions in mitral valve surgery - A European perspective.

INTRODUCTION: In recent years, major findings on concomitant procedures and anticoagulation management have occurred in Mitral Valve (MV) surgery. Therefore, we sought to evaluate the current practices in MV interventions across Europe. METHODS: In October 2021, all national cardio-thoracic societies in the European region were identified following an electronic search and sent an online survey of 14 questions to distribute among their member consultant/attending cardiac surgeons. RESULTS: The survey was completed by 91 consultant/attending cardiac surgeons across 12 European countries, with 78% indicating MV repair as their specialty area. 57.1% performed >150 operations/year and 71.4% had 10+ years of experience.Concomitant tricuspid valve repair is performed for moderate tricuspid regurgitation (TR) by 69% of surgeons and for mild TR by 26.3%, both with annular diameter >40 mm. 50.6% indicated ischaemic MV surgery in patients undergoing CABG if moderate mitral regurgitation with ERO >20 mm2 and regurgitant volume >30 mL, and 45.1% perform it if severe MR with ERO >40 mm2 and regurgitant volume >60 mL. For these patients the preferred management was: MVR if predictors of repair failure identified (47.2%) and downsizing annuloplasty ring only (34.1%).For atrial fibrillation (AF) in cardiac surgery, 34.1% perform ablation with biatrial lesion and 20% with left sided only. 62.6% perform concomitant Left Atrial Appendage (LAA) Occlusion irrespective of AF ablation with a left atrial clip. A wide variability in anticoagulation strategies for MV repair and bioprosthetic MV valve was reported both for patients in sinus rhythm and AF. CONCLUSION: These results demonstrate a variable practice for MV surgery, and a degree of lack of compliance with surgical intervention guidelines and anticoagulation strategy.

All-organic transparent plant e-skin for noninvasive phenotyping.

Real-time in situ monitoring of plant physiology is essential for establishing a phenotyping platform for precision agriculture. A key enabler for this monitoring is a device that can be noninvasively attached to plants and transduce their physiological status into digital data. Here, we report an all-organic transparent plant e-skin by micropatterning poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) on polydimethylsiloxane (PDMS) substrate. This plant e-skin is optically and mechanically invisible to plants with no observable adverse effects to plant health. We demonstrate the capabilities of our plant e-skins as strain and temperature sensors, with the application to Brassica rapa leaves for collecting corresponding parameters under normal and abiotic stress conditions. Strains imposed on the leaf surface during growth as well as diurnal fluctuation of surface temperature were captured. We further present a digital-twin interface to visualize real-time plant surface environment, providing an intuitive and vivid platform for plant phenotyping.

BODIPY-fused uracil: synthesis, photophysical properties, and applications.

Fluorescent nucleobase and nucleic acid analogs are important tools in chemical and molecular biology as fluorescent labelling of nucleobases has applications in cellular imaging and anti-tumor activity. Boron-dipyrromethene (BODIPY) dyes exhibiting high brightness and good photostability are extensively used as fluorescent labelling agents and as type II photosensitizers for photodynamic therapy. Thus, the combination of nucleobases and BODIPY to obtain new compounds with both anti-tumor activity and fluorescent imaging functions is the focus of our research. We synthesized two new nucleobase analogs 1 and 2 by fusing the BODIPY core directly with uracil which resulted in favorable photophysical properties and high emission quantum efficiencies particularly in organic solvents. Further, we explored the newly synthesized derivatives, which possessed good singlet oxygen generation efficiencies and bio-compatibility, as potential PDT agents and our results show that they exhibit in vitro anti-tumor activities.

Left ventricular assist device implantation and concomitant mitral valve surgery: A systematic review and meta-analysis.

BACKGROUND: The management of concomitant valvular lesions in patients undergoing left ventricular assist device (LVAD) implantation remains a topic of debate. This systematic review and meta-analysis aimed to evaluate the existing evidence on postoperative outcomes following LVAD implantation, with and without concomitant MV surgery. METHODS: A systematic database search was conducted as per PRISMA guidelines, of original articles comparing LVAD alone to LVAD plus concomitant MV surgery up to February 2023. The primary outcomes assessed were overall mortality and early mortality, while secondary outcomes included stroke, need for right ventricular assist device (RVAD) implantation, postoperative mitral valve regurgitation, major bleeding, and renal dysfunction. RESULTS: The meta-analysis included 10 studies comprising 32 184 patients. It revealed that concomitant MV surgery during LVAD implantation did not significantly affect overall mortality (OR:0.83; 95% CI: 0.53 to 1.29; p = 0.40), early mortality (OR:1.17; 95% CI: 0.63 to 2.17; p = 0.63), stroke, need for RVAD implantation, postoperative mitral valve regurgitation, major bleeding, or renal dysfunction. These findings suggest that concomitant MV surgery appears not to confer additional benefits in terms of these clinical outcomes. CONCLUSION: Based on the available evidence, concomitant MV surgery during LVAD implantation does not appear to have a significant impact on postoperative outcomes. However, decision-making regarding MV surgery should be individualized, considering patient-specific factors and characteristics. Further research with prospective studies focusing on specific patient populations and newer LVAD devices is warranted to provide more robust evidence and guide clinical practice in the management of valvular lesions in LVAD recipients.

SIRT1 inhibits mitochondrial hyperfusion associated mito-bulb formation to sensitize oral cancer cells for apoptosis in a mtROS-dependent signalling pathway.

SIRT1 (NAD-dependent protein deacetylase sirtuin-1), a class III histone deacetylase acting as a tumor suppressor gene, is downregulated in oral cancer cells. Non-apoptotic doses of cisplatin (CDDP) downregulate SIRT1 expression advocating the mechanism of drug resistance. SIRT1 downregulation orchestrates inhibition of DNM1L-mediated mitochondrial fission, subsequently leading to the formation of hyperfused mitochondrial networks. The hyperfused mitochondrial networks preserve the release of cytochrome C (CYCS) by stabilizing the mitochondrial inner membrane cristae (formation of mitochondrial nucleoid clustering mimicking mito-bulb like structures) and reducing the generation of mitochondrial superoxide to inhibit apoptosis. Overexpression of SIRT1 reverses the mitochondrial hyperfusion by initiating DNM1L-regulated mitochondrial fission. In the overexpressed cells, inhibition of mitochondrial hyperfusion and nucleoid clustering (mito-bulbs) facilitates the cytoplasmic release of CYCS along with an enhanced generation of mitochondrial superoxide for the subsequent induction of apoptosis. Further, low-dose priming with gallic acid (GA), a bio-active SIRT1 activator, nullifies CDDP-mediated apoptosis inhibition by suppressing mitochondrial hyperfusion. In this setting, SIRT1 knockdown hinders apoptosis activation in GA-primed oral cancer cells. Similarly, SIRT1 overexpression in the CDDP resistance oral cancer-derived polyploid giant cancer cells (PGCCs) re-sensitizes the cells to apoptosis. Interestingly, synergistically treated with CDDP, GA induces apoptosis in the PGCCs by inhibiting mitochondrial hyperfusion.

Evaluating the Efficacy of Platelet-Rich Fibrin Matrix versus Subepithelial Connective Tissue Grafts in Dental Root Coverage: A Comparative Study Using Modified Ruben's Technique.

BACKGROUND Dental root coverage, crucial in managing gingival recessions, traditionally utilizes subepithelial connective tissue grafts. However, this approach has limitations such as donor site morbidity and graft availability. Recent studies have introduced platelet-rich fibrin (PRF) as an alternative, leveraging its regenerative potential and growth factors. Despite the promise, comparative assessments between PRF and conventional grafts remain limited. This research probes whether PRF, when used beneath a modified Ruben's mixed flap, could provide comparable or superior dental root coverage than a subepithelial connective tissue graft. MATERIAL AND METHODS We enrolled 30 patients exhibiting Miller's class I and II recession in this comparative case series. Patients were randomly assigned to receive either a connective tissue graft (15 patients) or a PRF matrix (15 patients), both covered by a modified Ruben's mixed flap. RESULTS Clinical parameters, including full mouth plaque scores, bleeding scores, probing sulcus depth, clinical attachment level, gingival position assessment, width, and thickness of attached gingiva, were assessed in both the control and test groups at baseline, 6 months, and 12 months post-surgery. Significant differences were observed at all intervals.At the 12-month mark, the control group (connective tissue graft) achieved 91% complete root coverage, while the test group (PRF matrix) achieved 86%. However, this difference was not statistically significant. CONCLUSIONS The study outcomes suggest comparable gains in root coverage and attached gingiva between the connective tissue graft and PRF matrix groups. Thus, the results support our hypothesis that a subepithelial PRF matrix can serve as a viable alternative to a subepithelial connective tissue graft for treating dental root coverage.

Luminescent hexagonal microtubes prepared through water-induced self-assembly of a polymorphic organoboron compound: formation mechanism and waveguide behaviour.

Tetra-coordinated organoboron (TCOB) compounds are promising candidates for developing high-performance optical devices due to their excellent optoelectronic performance. Fabricating TCOB-based nanomaterials of controlled and defined morphology through rapid and easy-to-execute protocols can significantly accelerate their practical utility in the aforesaid applications. Herein, we report water-induced self-assembly (WISA) to convert a polymorphic TCOB complex (HNBI-B, derived from a 2-(2'-hydroxy-naphthyl)-benzimidazole precursor) into two unique nanomorphologies viz. nanodiscoids (NDs) and fluorescent microtubes with hexagonal cross-sections (HMTs). Detailed electron microscopic investigations revealed that oriented assembly and fusion of the initially formed NDs yield the blue emissive HMTs (SSQY = 26.7%) that exhibited highly promising photophysical behaviour. For example, the HMTs outperformed all the crystal polymorphs of HNBI-B obtained from CHCl3, EtOAc and MeOH in emissivity and also exhibited superior waveguide behaviour, with a much lower optical loss coefficient α' = 1.692 dB mm-1 compared to the rod-shaped microcrystals of HNBI-B obtained from MeOH (α' = 1.853 dB mm-1). Thus, this work reports rapid access to high performance optical nanomaterials through WISA, opening new avenues for creating useful nanomaterial morphologies with superior optical performance.

Exploring microbial diversity in hot springs of Surajkund, India through 16S rRNA analysis and thermozyme characterization from endogenous isolates.

Hot springs are a valuable source of biologically significant chemicals due to their high microbial diversity. To investigate the possibilities for industrial uses of these bacteria, researchers collected water and sediment samples from variety of hot springs. Our investigation employed both culture-dependent and culture-independent techniques, including 16S-based marker gene analysis of the microbiota from the hot springs of Surajkund, Jharkhand. In addition, we cultivated thermophilic isolates and screened for their ability to produce amylase, xylanase, and cellulase. After the optimized production of amylase the enzyme was partially purified and characterized using UPLC, DLS-ZP, and TGA. The retention time for the amylase was observed to be around 0.5 min. We confirmed the stability of the amylase at higher temperatures through observation of a steady thermo gravimetric profile at 400 °C. One of the thermophilic isolates obtained from the kund, demonstrated the potential to degrade lignocellulosic agricultural waste.

Structural insight into the cooperativity of spin crossover compounds.

Spin-crossover (SCO) compounds are promising materials for a wide variety of industrial applications. However, the fundamental understanding of their nature of transition and its effect on the physical properties are still being fervently explored; the microscopic knowledge of their transition is essential for tailoring their properties. Here an attempt is made to correlate the changes in macroscopic physical properties with microscopic structural changes in the orthorhombic and monoclinic polymorphs of the SCO compound Fe(PM-Bia)2(NCS)2 (PM = N-2'-pyridylmethylene and Bia = 4-aminobiphenyl) by employing single-crystal X-ray diffraction, magnetization and DSC measurements. The dependence of macroscopic properties on cooperativity, highlighting the role of hydrogen bonding, π-π and van der Waals interactions is discussed. Values of entropy, enthalpy and cooperativity are calculated numerically based on the Slichter-Drickamer model. The particle size dependence of the magnetic properties is probed along with the thermal exchange and the kinetic behavior of the two polymorphs based on the dependence of magnetization on temperature scan rate and a theoretical model is proposed for the calculation of the non-equilibrium spin-phase fraction. Also a scan-rate-dependent two-step behavior observed for the orthorhombic polymorph, which is absent for the monoclinic polymorph, is reported. Moreover, it is found that the radiation dose from synchrotron radiation affects the spin-crossover process and shifts the transition region to lower temperatures, implying that the spin crossover can be tuned with radiation damage.

High-affinity potassium transporter from a mangrove tree Avicennia officinalis increases salinity tolerance of Arabidopsis thaliana.

Salinity reduces the growth and productivity of crop plants worldwide. Mangroves have evolved efficient ion homeostasis mechanisms to survive under their natural saline growth habitat. Information obtained from them may be utilized for increasing the salt tolerance of crop plants. We identified and characterized a high-affinity potassium transporter gene (AoHKT1) from Avicennia officinalis. The expression of AoHKT1 was induced by NaCl mainly in the leaves. Functional study by heterologous expression of AoHKT1 in Arabidopsis T-DNA insertional mutants athkt1-1 and athkt1-4 revealed that it could enhance the salt tolerance of the mutant plants. This was accompanied by an increase in K+ accumulation in the leaves. AoHKT1 was localized to the plasma membrane in Arabidopsis, and when expressed in yeast, it could complement the functions of both Na+ and K+ transporters. An attempt was made to identify the upstream regulator of AtHKT1, a close homolog of AoHKT1. Using chromatin immunoprecipitation, luciferase assay and yeast one-hybrid assays, WRKY9 was identified as the main transcription factor in the process. Furthermore, this was corroborated by the observation that AtHKT1 levels were significantly reduced in the atwrky9 seedlings. These findings revealed a part of the molecular regulatory mechanism of HKT1 induction in response to salt treatment in Arabidopsis. Our study suggests that AoHKT1 is a potential candidate for generating crop plants with increased salt tolerance.

Single-cell analysis of the nervous system at small and large scales with instant partitions.

Single-cell RNA sequencing is a new frontier across all biology, particularly in neuroscience. While powerful for answering numerous neuroscience questions, limitations in sample input size, and initial capital outlay can exclude some researchers from its application. Here, we tested a recently introduced method for scRNAseq across diverse scales and neuroscience experiments. We benchmarked against a major current scRNAseq technology and found that PIPseq performed similarly, in line with earlier benchmarking data. Across dozens of samples, PIPseq recovered many brain cell types at small and large scales (1,000-100,000 cells/sample) and was able to detect differentially expressed genes in an inflammation paradigm. Similarly, PIPseq could detect expected and new differentially expressed genes in a brain single cell suspension from a knockout mouse model; it could also detect rare, virally-la-belled cells following lentiviral targeting and gene knockdown. Finally, we used PIPseq to investigate gene expression in a nontraditional model species, the little skate (Leucoraja erinacea). In total, PIPSeq was able to detect single-cell gene expression changes across models and species, with an added benefit of large scale capture and sequencing of each sample.

Co-targeting autophagy and NRF2 signaling triggers mitochondrial superoxide to sensitize oral cancer stem cells for cisplatin-induced apoptosis.

Cancer stem cell (CSC) populations are regulated by autophagy, which in turn modulates tumorigenicity and malignancy. In this study, we demonstrated that cisplatin treatment enriches the CSCs population by increasing autophagosome formation and speeding up autophagosome-lysosome fusion by recruiting RAB7 to autolysosomes. Further, cisplatin treatment stimulates lysosomal activity and increases autophagic flux in oral CD44+ cells. Interestingly, both ATG5- and BECN1-dependent autophagy are essential for maintaining cancer stemness, self-renewal, and resistance to cisplatin-induced cytotoxicity in oral CD44+ cells. Moreover, we discovered that autophagy-deficient (shATG5 and/or shBECN1) CD44+ cells activates nuclear factor, erythroid 2 like 2 (NRF2) signaling, which in turn reduces the elevated reactive oxygen species (ROS) level enhancing cancer stemness. Genetic inhibition of NRF2 (siNRF2) in autophagy-deficient CD44+ cells increases mitochondrial ROS (mtROS) level, reducing cisplatin-resistance CSCs, and pre-treatment with mitoTEMPO [a mitochondria-targeted superoxide dismutase (SOD) mimetic] lessened the cytotoxic effect enhancing cancer stemness. We also found that inhibiting autophagy (with CQ) and NRF2 signaling (with ML-385) combinedly increases cisplatin cytotoxicity, thereby suppressing the expansion of oral CD44+ cells; this finding has the potential to be clinically applicable in resolving CSC-associated chemoresistance and tumor relapse in oral cancer.

The inner mitochondrial membrane fission protein MTP18 serves as a mitophagy receptor to prevent apoptosis in oral cancer.

MTP18 (also known as MTFP1), an inner mitochondrial membrane protein, plays a vital role in maintaining mitochondrial morphology by regulating mitochondrial fission. Here, we found that MTP18 functions as a mitophagy receptor that targets dysfunctional mitochondria into autophagosomes for elimination. Interestingly, MTP18 interacts with members of the LC3 (also known as MAP1LC3) family through its LC3-interacting region (LIR) to induce mitochondrial autophagy. Mutation in the LIR motif (mLIR) inhibited that interaction, thus suppressing mitophagy. Moreover, Parkin or PINK1 deficiency abrogated mitophagy in MTP18-overexpressing human oral cancer-derived FaDu cells. Upon exposure to the mitochondrial oxidative phosphorylation uncoupler CCCP, MTP18[mLIR]-FaDu cells showed decreased TOM20 levels without affecting COX IV levels. Conversely, loss of Parkin or PINK1 resulted in inhibition of TOM20 and COX IV degradation in MTP18[mLIR]-FaDu cells exposed to CCCP, establishing Parkin-mediated proteasomal degradation of outer mitochondrial membrane as essential for effective mitophagy. We also found that MTP18 provides a survival advantage to oral cancer cells exposed to cellular stress and that inhibition of MTP18-dependent mitophagy induced cell death in oral cancer cells. These findings demonstrate that MTP18 is a novel mitophagy receptor and that MTP18-dependent mitophagy has pathophysiologic implications for oral cancer progression, indicating inhibition of MTP18-mitophagy could thus be a promising cancer therapy strategy.

Adsorptive removal of acid blue dye 113 using three agricultural waste biomasses: The possibility of valorization by activation and carbonization - A comparative analysis.

The presence of various organic and inorganic contaminants in wastewater leads to serious health effects on humans and ecosystems. Industrial effluents have been considered as noticeable sources of contaminating water streams. These effluents directly liberate the pollutants such as dye molecules and heavy metal ions into the environment. In the present study, three biowaste materials (groundnut shell powder, coconut coir powder and activated corn leaf carbon) were utilized and compared for the removal of acid blue dye 113 from aqueous solutions. The characterization study of newly prepared sorbent material (H3PO4-activated corn leaf carbon) and the other utilized sorbents was carried out by Scanning Electron Microscope (SEM) and Fourier Transform Infrared Spectrophotometer (FTIR), along with Energy Dispersive X-Ray (EDX) Analysis. The influence of experimental conditions such as pH, initial dye concentration, temperature, contact time, and sorbent dosage on the removal efficiency of the dye were appraised. The adsorption isotherm and kinetic result of acid blue dye 113 adsorption onto the sorbents best obeyed from Sips and pseudo-second-order kinetic model. Overall, the outcomes confirmed that the newly synthesized sorbent material (carbonized H3PO4-activated corn leaf) has superior adsorption capacity, rapid adsorption, and higher suitability for the removal of toxic dyes from the contaminated waters.