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Abstract Constructed wetlands (CWs) are engineered environments designed to utilise natural processes to treat urban or industrial wastewater, with the core driver of the bioremediation process provided by the microorganisms present within. This study isolated 32 bacterial strains from sediment across the Sardar Bherry CW to find candidates with remediation properties and to understand how the physiochemical gradient from wastewater input influences the functional properties of the bacteria present. Bacterial isolates recovered closer to the wastewater effluence were more likely to be pathogenic, with increased haemolytic activity, causing high rates of fish mortality. In contrast, isolates recovered further from the wastewater source were observed to be non-pathogenic and have increased inhibitory effect against pathogenic strains. Extracellular proteins extracted from non-pathogenic isolates also appeared to be effective at inhibiting the growth of pathogenic bacteria, including multidrug resistant strains. Non-pathogenic isolates recovered across all sampling sites displayed the ability to reduce high levels of ammonia in solution during laboratory testing. Antibiogram assays of the recovered isolates showed a relatively high rate of multidrug resistant or marginally resistant bacteria across all sampling sites, highlighting a potential limitation within the CW bioremediation process in mitigating antibiotic resistant strains. This isolate based study provided an avenue to understand the influence of spatial succession from wastewater effluence on bacterial characteristics, as well as obtain candidates that can be further investigated for optimisation in bioremediation efforts. The cultured isolates can supplement future environmental sequencing studies by providing wet lab specimens to compare (meta)genomic information discovered within the CW ecosystem.

Herein, a water-soluble, ultrabright, near-infrared (NIR) fluorescent, mechanically interlocked molecules (MIMs)-peptide bioconjugate is designed with dual targeting capabilities. Cancer cell surface overexpressed α V β 3 integrin targeting two RGDS tetrapeptide residues is tethered at the macrocycle of MIMs-peptide bioconjugate via Cu(I)-catalyzed click chemistry on the Wang resin, and mitochondria targeting lipophilic cationic TPP + functionality is conjugated at the axle dye. Living carcinoma cell selective active targeting, subsequently cell penetration, mitochondrial imaging, including the ultrastructure of cristae, and real-time tracking of malignant mitochondria by MIMs-peptide bioconjugate (RGDS) 2 -Mito-MIMs-TPP + are established by stimulated emission depletion (STED) super-resolved fluorescence microscopy. Water-soluble NIR (RGDS) 2 -Mito-MIMs-TPP + is an effective class of MIMs-peptide bioconjugate with promising photophysics; for instance, remarkable photostability and thermal stability, strong and narrow NIR abs/em bands with high quantum yield, ultrabrightness, decent fluorescence lifetime, reasonable stability against cellular nucleophiles, biocompatibility, noncytotoxicity, and dual-targeted living cancer cell submitochondrial imaging ability are all indispensable criteria for targeted super-resolved STED microscopy.

A striking issue is the scarcity of imaging probes for the early diagnosis of Alzheimer's disease. For the development of Aβ biomarkers, a mitochondria targeting, de novo designed, aggregation-induced emission (AIE) probe Cou-AIE-TPP + is constructed by engineering the aromatic coumarin framework into the bridge of electron donor-acceptor-donor tethered with a lipophilic cationic triphenylphosphonium (TPP + ) group. The synthesized Cou-AIE-TPP + probe exhibits biocompatibility, noncytotoxicity, and a huge Stokes shift (124 nm in PBS). Cou-AIE-TPP + has respectable fluorescence augmentation inside the aggregated Aβ40 in comparison with monomeric Aβ40 with a high binding affinity ( K = 83 nM) to Aβ40 aggregates, is capable of detecting the kinetics of amyloid aggregation, and is superior to the gold standard probe thioflavin T. Fluorescence lifetime and brightness are also augmented when the probe Cou-AIE-TPP d = 83 nM) to Aβ40 aggregates, is capable of detecting the kinetics of amyloid aggregation, and is superior to the gold standard probe thioflavin T. Fluorescence lifetime and brightness are also augmented when the probe Cou-AIE-TPP + binds with Aβ aggregates in PBS. Cou-AIE-TPP + 604 nm) selectively targets and images neuronal cell mitochondria, is useful to monitor mitochondrial morphology alteration and damage during Aβ40-induced neurotoxicity, recognizes neurotoxic Aβ fibrils, and is highly colocalized with thioflavin T, showing a decent Pearson correlation coefficient of 0.91 in the human neuroblastoma SH-SY5Y cell line. These findings indicate that the mitochondria targeting, λ em 604 nm) selectively targets and images neuronal cell mitochondria, is useful to monitor mitochondrial morphology alteration and damage during Aβ40-induced neurotoxicity, recognizes neurotoxic Aβ fibrils, and is highly colocalized with thioflavin T, showing a decent Pearson correlation coefficient of 0.91 in the human neuroblastoma SH-SY5Y cell line. These findings indicate that the mitochondria targeting, de novo designed, functional AIE-based solvatofluorochromic Cou-AIE-TPP + probe is a promising switch on biomarkers for fluorescence imaging of Aβ aggregates and to monitor mitochondrial morphology change and dysfunction during Aβ-induced neurotoxicity, which may offer imperative direction for the advancement of compelling AIE biomarkers for targeted early stage Aβ diagnosis in the future.

Aim Orthodontic treatment relies heavily on the mechanical properties and surface characteristics of archwire materials to achieve optimal outcomes. This study aimed to comprehensively evaluate the mechanical properties, including tensile strength, yield strength, and modulus of elasticity, as well as the surface characteristics, such as surface roughness and frictional properties, of different archwire materials. Methods Four types of archwire materials, stainless steel, nickel-titanium (NiTi), beta-titanium, and esthetic archwires, were subjected to mechanical testing and surface analysis, with 31 in each group. Tensile testing was conducted to determine the maximum tensile strength, yield strength, and elastic modulus of each material. Surface roughness analysis was performed using profilometry techniques, and frictional properties were evaluated using an orthodontic friction testing apparatus. Results Stainless steel exhibited the highest tensile strength (900 N), followed by beta-titanium (850 N), NiTi (800 N), and esthetic archwire (750 N). Stainless steel also demonstrated the highest yield strength (780 N), followed by beta-titanium (740 N), NiTi (710 N), and esthetic archwire (650 N). The modulus of elasticity was the highest for stainless steel (200 GPa), followed by beta-titanium (170 GPa), NiTi (150 GPa), and esthetic archwires (120 GPa). Surface roughness was lowest in stainless steel archwires (mean Ra value of 0.25 µm), leading to reduced frictional resistance, whereas esthetic archwires exhibited the highest surface roughness (mean Ra value of 0.40 µm) and frictional forces. Significant differences in the mechanical properties and surface characteristics were observed among the materials (p < 0.05). Conclusions The choice of archwire material significantly influences orthodontic treatment outcomes by affecting the efficiency and effectiveness of tooth movement. Stainless steel and beta-titanium wires are ideal for high-stress applications, providing the robust mechanical strength necessary for complex movements. In contrast, NiTi wires, with their superelasticity, offer consistent and gentle forces, enhancing patient comfort and accelerating the alignment phase. Esthetic archwires, while visually appealing, often compromise mechanical performance, potentially prolonging treatment duration., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, V S et al.)

We have synthesized an acidic pH-activatable dual targeting ratiometric fluorescent probe-peptide conjugate using the SPPS protocol on Rink amide AM resin. Living carcinoma cell specific active targeting, successive cell penetration, and selective staining of lysosomes are accomplished. Real-time monitoring of lysosomes, 3D, and multicolor cancer cell imaging are also attained. The de novo design consists of the integration of multifunctionality into a single molecular scaffold, e. g., RGDS peptide residue to target cancer cell surface overexpressed receptor α V β 3 integrin, live-cell penetrating organic unsymmetrical rhodamine-hemicyanine chromophore comprising a lysosome targeting morpholine group, and an acidic pH openable spiro-lactam ring for a visible-to-NIR switchable ratiometric response. Water-soluble fluorescent probe-peptide conjugate exhibits intramolecular spirolactamization at basic pH through Arg amide N. The visible spirolactam state predominantly exists at physiological and basic pH and can be switched to the highly conjugated NIR open amide state (λ em =735 nm) through spiro-lactam ring opening triggered by acidic pH with a huge bathochromic shift (Δλ abs =336 nm, Δλ FL =265 nm). Moreover, pH-sensitive ratiometric optical switching is achieved. This in situ acidic cancer cell lysosome activatable multifunctional fluorophore-peptide conjugate shows augmented molar absorptivity, enhanced quantum yield, and improved fluorescence lifetime at acidic lysosomal pH; negligible cytotoxicity; and dual targeted ratiometric imaging capability of living cancer cell selective lysosomes with a pK a value of 5.1., (© 2024 Wiley-VCH GmbH.)

A new method for producing parts in the expanding sector is additive manufacturing. The appropriate name for three-dimensional (3D) printing is additive manufacturing because it produces the part layer by layer. Plastics and metals can be 3D printed in large quantities with the precise surface finish and feature quality needed in additive manufacturing. More specifically, direct metal sintering, direct energy deposition, and metal binder jetting are used in 3D printing. The computer-aided design model is completed when the powder bed has been successively scanned and lowered. The metal sintering process uses a powder bed with powder metal, and laser selectively melts a flattened bed of powder, which is done with roller with successive rolling of new layer on previous into desired shape before a new layer is pushed on top of the previous layer. As a result, the new layer has solidified on top of the earlier layer, causing the prior layer to melt back again. Because of the unique thermal cycle, this results in residual stress (RS). The unique thermal cycle of metal additive manufacturing is characterized by (1) rapid heating rate caused by high energy intensity and steep temperature gradients; (2) rapid solidification with high cooling rates because of the small volume of melt pool; and (3) melt back, which involves simultaneous melting of the top powder layer and re-melting of underlying previously solidified layers. The presence of RS in metal additive manufacturing (AM) creates difficulties that restrict the process's ability to produce parts at an industrial scale. During and after manufacturing, these forces may cause parts to distort and crack. This can be solved by heating the powder bed, which will lessen this type of issue. The causes, traits, and reduction of RS are the main topics of this review article. A number of conceptual approaches to reducing RS are addressed to provide some useful inspiration for creating a methodical RS balancing procedure for AM. These approaches are based on the state and future of the relevant techniques., (Copyright 2023, Mary Ann Liebert, Inc., publishers.)

Cavity-electromechanical systems are extensively used for sensing and controlling the vibrations of mechanical resonators down to their quantum limit. The nonlinear radiation-pressure interaction in these systems could result in an unstable response of the mechanical resonator showing features such as frequency-combs, period-doubling bifurcations and chaos. However, due to weak light-matter interaction, typically these effects appear at very high driving strengths. By using polariton modes formed by a strongly coupled flux-tunable transmon and a microwave cavity, here we demonstrate an electromechanical device and achieve a single-photon coupling rate g 0 / 2 π of 160 kHz, which is nearly 4% of the mechanical frequency ω m . Due to large g 0 /ω m ratio, the device shows an unstable mechanical response resulting in frequency combs in sub-single photon limit. We systematically investigate the boundary of the unstable response and identify two important regimes governed by the optomechanical backaction and the nonlinearity of the electromagnetic mode. Such an improvement in the single-photon coupling rate and the observations of microwave frequency combs at single-photon levels may have applications in the quantum control of the motional states and critical parametric sensing. Our experiments strongly suggest the requirement of newer approaches to understand instabilities., (© 2024. The Author(s).)

Curcumin and epigallocatechin gallate have the disadvantage of low aqueous solubility and first-pass metabolism, resulting in limited bioavailability. This work aimed to enhance oral bioavailability by forming gastric pH-stable shellac nanoparticles containing curcumin and epigallocatechin gallate using locust bean gum by anti-solvent precipitation (CESL-NP). The nanoparticles were characterized by their particle size, morphology, zeta potential, gastric pH stability, release profile, drug loading, and entrapment efficiency. The findings showed that a network of hydrolyzed shellac, locust bean gum, curcumin, and epigallocatechin gallate successfully entrapped individual particles inside a complex system. The morphological investigation of the CESL-NP formulation using FESEM, TEM, and AFM revealed the presence of spherical particles. FTIR, DSC, and XRD analysis revealed that curcumin and epigallocatechin gallate were amorphous due to their bond interactions with the matrix. Streptozotocin-treated mice, upon treatment with CESL-NP, showed kidney and pancreatic improvements with normalized kidney hypertrophy index and histopathology, maintained biochemical parameters, increased beta cell count, and a 38.68-fold higher blood glucose level inhibition were observed when compared to free-(CUR + EGCG). This research affirms that the shellac-locust bean gum complex shows potential for the sustained oral delivery of curcumin and epigallocatechin gallate, specifically for treating diabetic nephropathy., Competing Interests: Declaration of competing interest The authors have declared no conflict of interest in this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In recent years biochar (BC) has gained importance for its huge carbon (C) sequestration potential and positive effects on various soil functions. However, there is a paucity of information on the long-term impact of BC on the priming effect and nutrient availability in soil with different properties. This study investigates the effects of BC prepared from rice husk (RBC4, RBC6), sugarcane bagasse (SBC4, SBC6) and mustard stalk (MBC4, MBC6) at 400 and 600 °C on soil C priming and nitrogen (N), phosphorus (P), and potassium (K) availability in an Alfisol, Inceptisol, and Mollisol. BC properties were analyzed, and its decomposition in three soil orders was studied for 290 days in an incubation experiment. Post-incubation, available N, P, and K in soil were estimated. CO 2 evolution from BC and soil alone was also studied to determine the direction of priming effect on native soil C. Increasing pyrolysis temperature enhanced pH and EC of most of the BC. The pyrolysis temperature did not show clear trend with respect to priming effect and nutrient availability across feedstock and soil type. MBC6 increased C mineralization in all the soil orders while RBC6 in Alfisol and SBC6 in both Inceptisol and Mollisol demonstrated high negative priming, making them potential amendments for preserving native soil C. Most of the BC showed negative priming of native SOC in long run (290 days) but all these BC enhanced the available N, P, and K in soil. SBC4 enhanced N availability in Alfisol and Inceptisol, RBC4 improved N and P availability in Mollisol and P in Alfisol and MBC6 increased K availability in all the soils. Thus, based on management goals, tailored BC or blending different BC can efficiently improve C sequestration and boost soil fertility., (© 2024. The Author(s).)

Background: Recycling transplant kidneys, in other words using an allograft which has previously been transplanted in one recipient for transplant in a second recipient, can be a source of opportunity for expanding the pool of available grafts in the United States and beyond., Summary: We describe a case of renal transplantation from a donor who had undergone a kidney transplant 3 years prior and had good graft function at the time of procurement. The recipient underwent transplantation uneventfully and to date has demonstrated excellent graft function. We also include a literature review of reported cases of recycled/retransplanted kidneys., Key Messages: -Recycling transplanted kidneys is a largely untapped resource which could help decrease the transplant waitlist. -Utilizing such kidneys does need special considerations in terms of procurement technique, backtable, crossmatch, recipient selection and follow-up., (The Author(s). Published by S. Karger AG, Basel.)

Currently, around 400 million tonnes of synthetic polymers are being dumped as waste annually and by this rate by 2050 the ocean would contain more such waste compared to the total weight of fish. As recycling could solve part of this problem, recently such waste is being reused for various purposes like composite preparation, oil production and various other use such as production of foams, sponges, and aerogels. However, there is a relatively limited literature available on the utilization of polyethylene polymer (like LDPE). The study presented in this article indicated that LDPE-based polymers could be reused (after modification) for preparation of hydrophobic, lightweight, and porous aerogels that have oil-spills and organic solvent adsorption capacity. The aerogels showed contact angle of 121.9 o , bulk density below 0.25 g/cm 3 , and were found to be semi-crystalline. The aerogels showed oil and solvent adsorption more than that for their untreated counterparts. Also, the aerogels were found to be recycled for more than five cycles with very minimum loss of efficacy. This area of producing oil sorbents from single used plastic wastes is still very open for further research and seems to be a promising route for both waste reduction, and the synthesis of value-added products. This could be one of the most sustainable approaches for efficient single-used plastic wase management and environment clean-up., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Integrating an NIR fluorescent probe with a magnetic resonance imaging (MRI) agent to harvest complementary imaging information is challenging. Here, we have designed water-soluble, biocompatible, noncytotoxic, bright-NIR-emitting, sugar-functionalized, mechanically interlocked molecules (MIMs)-capped superparamagnetic ultrasmall Fe 3 O 4 NPs for targeted multimodal imaging. Dual-functional stoppers containing an unsymmetrical NIR squaraine dye interlocked within a macrocycle to construct multifunctional MIMs are developed with enhanced NIR fluorescence efficiency and durability. One of the stoppers of the axle is composed of a lipophilic cationic TPP + functionality to target mitochondria, and the other stopper comprises a dopamine-containing catechol group to anchor at the surface of the synthesized Fe 3 O 4 NPs. Fe 3 O 4 NPs surface-coated with targeted NIR rotaxanes help to deliver ultrasmall magnetic NPs specifically inside the mitochondria. Two carbohydrate moieties are conjugated with the macrocycle of the rotaxane via click chemistry to improve the water solubility of MitoSQRot-(Carb-OH) 2 -DOPA-Fe 3 O 4 NPs. Water-soluble, rotaxane-capped Fe 3 O 4 NPs are used for live-cell mitochondria-targeted NIR fluorescence confocal imaging, 3D and multicolor imaging in combination with T -weighted MRI on a 9.4 T MR scanner with a high relaxation rate ( 2 -weighted MRI on a 9.4 T MR scanner with a high relaxation rate ( r 2 ) of 180.7 mM -1 s -1 . Biocompatible, noncytotoxic, ultrabright NIR rotaxane-capped superparamagnetic ultrasmall monodisperse Fe 3 O 4 NPs could be a promising agent for targeted multimodal imaging applications.

Here, our designed water-soluble NIR fluorescent unsymmetrical Cy-5-Mal/TPP + consists of a lipophilic cationic TPP + subunit that can selectively target and accumulate in a live-cell inner mitochondrial matrix where a maleimide residue of the probe undergoes faster chemoselective and site-specific covalent attachment with the exposed Cys residue of mitochondrion-specific proteins. On the basis of this dual localization effect, Cy-5-Mal/TPP + molecules remain for a longer time period even after membrane depolarization, enabling long-term live-cell mitochondrial imaging. Due to the adequate concentration of Cy-5-Mal/TPP + reached in live-cell mitochondria, it facilitates site-selective NIR fluorescent covalent labeling with Cys-exposed proteins, which are identified by the in-gel fluorescence assay and LC-MS/MS-based proteomics and supported by a computational method. This dual targeting approach with admirable photostability, narrow NIR absorption/emission bands, bright emission, long fluorescence lifetime, and insignificant cytotoxicity has been shown to improve real-time live-cell mitochondrial tracking including dynamics and interorganelle crosstalk with multicolor imaging applications.

With artificially engineered systems, it is now possible to realize the coherent interaction rate, which can become comparable to the mode frequencies, a regime known as ultrastrong coupling (USC). We experimentally realize a cavity-electromechanical device using a superconducting waveguide cavity and a mechanical resonator. In the presence of a strong pump, the mechanical-polaritons splitting can nearly reach 81% of the mechanical frequency, overwhelming all the dissipation rates. Approaching the USC limit, the steady-state response becomes unstable. We systematically measure the boundary of the unstable response while varying the pump parameters. The unstable dynamics display rich phases, such as self-induced oscillations, period-doubling bifurcation, and period-tripling oscillations, ultimately leading to the chaotic behavior. The experimental results and their theoretical modeling suggest the importance of residual nonlinear interaction terms in the weak-dissipative regime.

The spike (S) protein of severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) mediates a critical stage in infection, the fusion between viral and host membranes. The protein is categorized as a class I viral fusion protein and has two distinct cleavage sites that can be activated by proteases. The activation deploys the fusion peptide (FP) for insertion into the target cell membranes. Recent studies including our experiments showed that the FP was unable to modulate the kinetics of fusion at a low peptide-to-lipid ratio akin to the spike density at the viral surface. Therefore, we modified the C terminus of FP and attached a myristoyl chain (C-myr-FP) to restrict the C terminus near to the interface, bridge both membranes, and increase the effective local concentration. The lipidated FP (C-myr-FP) of SARS-CoV-2 greatly accelerates membrane fusion at a low peptide-to-lipid ratio as compared to the FP with no lipidation. Biophysical experiments suggest that C-myr-FP adopts a helical structure, perturbs the membrane interface, and increases water penetration to catalyze fusion. Scrambled peptide (C-myr-sFP) and truncated peptide (C-myr-8FP) could not significantly catalyze the fusion, thus suggesting the important role of myristoylation and the N terminus. C-myr-FP enhances murine coronavirus infection by promoting syncytia formation in L2 cells. The C-terminal lipidation of the FP might be a useful strategy to induce artificial fusion in biomedical applications., (© 2022 Wiley-VCH GmbH.)

We have demonstrated an efficient synthetic route with crystal structures for the construction of acidic pH-triggered visible-to-NIR interchangeable ratiometric fluorescent pH sensors. This bioresponsive probe exhibits pH-sensitive reversible absorption/emission features, low cytotoxicity, a huge 322 nm bathochromic spectral shift with augmented quantum yield from neutral to acidic pH, high sensitivity and selective targeting ability of live-cell lysosomes with ideal pK a , off-to-on narrow NIR absorption/fluorescence signals with high molar absorption coefficient at acidic lysosomal lumen, and in-situ live-cell pH-activated ratiometric imaging of lysosomal pH. Selective staining and ratiometric pH imaging in human carcinoma live-cell lysosomes were monitored by dual-channel confocal laser scanning microscope using a pH-activatable organic fluorescent dye comprising a morpholine moiety for lysosome targeting and an acidic pH openable oxazolidine ring. Moreover, real-time tracking of lysosomes, 3D, and multicolor live-cell imaging have been achieved using the synthesized pH-activatable probe., (© 2022 Wiley-VCH GmbH.)

Objectives: Cervical cancer is increasing worldwide and is becoming resistant to the existing drugs in clinical practice. Here, ethanolic extract of fruit body of Pleurotus florida was evaluated as antioxidant, anticancer agent against HeLa cell lines and anti-tumor against cervical cancer in mice model., Methods: Fruit bodies of P. florida in 90% ethanol, and the P. florida ethanolic extract (PFEE) was subsequently investigated for its antioxidant content and activity, anticancer properties against the cervical cancer cell line, HeLa, and antitumor activity against HeLa implanted mice., Results: The antioxidant activity bioassay showed that the IC 50 of PFEE was 41.17 ± 1.42a μg/ml. The cytotoxicity assay revealed that PFEE caused inhibition of cell proliferation. At the highest dose (1,250 μg/ml) after 24 h, 48 h, or 72 h of treatment, the percentages of cell growth inhibition were 75.22%, 77.77%, and 84.65%, respectively. It revealed that PFEE-treated cells became rounded and the nuclei became fragmented. PFEE induced intracellular generation of reactive oxygen species and reduced the mitochondrial membrane potential. PFEE also led to an up regulation of the apoptotic genes for caspases-3, -9, and Bax, whereas Bcl-2 gene was down regulated, and it also promoted the expression of p53. Cell cycle analysis revealed that cell cycle was arrested at the G 0 /G 1 checkpoint. PFEE suppressed metastasis and colonization. At a dosage of PFEE of 50 mg/kg of body weight, a 66.72% reduction in the size of tumors and an 87.44% reduction in the tumor weight were observed in mice., Conclusions: It has demonstrated that PFEE is a highly potent anti-cervical cancer agent in vitro and in vivo ., (Copyright: © International Journal of Health Sciences.)

Studies to date have not resolved how diverse transcriptional programs contribute to the intratumoral heterogeneity of small cell lung carcinoma (SCLC), an aggressive tumor associated with a dismal prognosis. Here, we identify distinct and commutable transcriptional states that confer discrete functional attributes in individual SCLC tumors. We combine an integrative approach comprising the transcriptomes of 52,975 single cells, high-resolution measurement of cell state dynamics at the single-cell level, and functional and correlative studies using treatment naïve xenografts with associated clinical outcomes. We show that individual SCLC tumors contain distinctive proportions of stable cellular states that are governed by bidirectional cell state transitions. Using drugs that target the epigenome, we reconfigure tumor state composition in part by altering individual state transition rates. Our results reveal new insights into how single-cell transition behaviors promote cell state equilibrium in SCLC and suggest that facile plasticity underlies its resistance to therapy and lethality.

Herein, development and detailed investigation of a S N '-type intramolecular aromatic substitution reaction involving α-arylazaoxyallyl cation intermediate, is disclosed. The study showcased that while α-aryl-α-chlorohydroxamate could be activated by a combination of base and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) into the corresponding azaoxyallyl cations, it could further emerge into a π-extended species involving the adjacent α-aryl moiety, and this transition is contingent on electronic effects of the aromatic ring as well as on α-substituents. An effective activation of the α-aromatic ring could pave the path for intramolecular Ar(Csp 2 )-N bond formation towards oxindoles. Control experiments and DFT calculations suggested that a non-pericyclic nucleophilic amination pathway is most likely operative and precluded the possibility of concerted or electrophilic amination mechanism. HFIP as the reaction solvent plays pivotal roles in the transformation., (© 2022 Wiley-VCH GmbH.)

Clinical trials on the therapeutic effect of curcumin have proven to be highly effective against many diseases including cancer and Alzheimer's. However, the molecular mechanism of interaction of curcumin with protein and live cell membrane is poorly understood. Here, we report the mechanism of interaction of curcumin with bovine serum albumin (BSA) and live E. coli cell membrane in the presence of organized assemblies of sodium dodecyl sulfate (SDS) and cetrimonium bromide (CTAB) by fluorescence spectroscopy, laser-scanning confocal microscopy, and computation. Enhanced binding constant, blue-shifted emission spectra, and imaging of heterogeneous FRET on live bacteria cell membrane strongly indicate the complex formation of curcumin with strong hydrophobic interaction, which is further validated by computation. Finally, our results may shed light on the efficient strategy of applications of curcumin as a natural therapeutic lead in clinical trials against many life-threatening diseases., (© 2022 Wiley-VCH GmbH.)

East Kolkata Wetland (EKW) is one of the largest sewage-fed wetlands in the world, which support the livelihood of thousands of peoples. However, at present, EKW system has become ecologically vulnerable due to the discharge of toxic waste through the sewage canal from the Kolkata metropolitan city. Hence, it becomes very important to understand the inflow and load of potentially toxic elements (PTE) in the sediment, water, and fish of sewage-fed wetland used for aquaculture activities. In this study, one of the polluted wetland from EKW, Sardar bherry, was selected as the study area. Sediment samples (45) were collected from 15 sites to characterize the PTEs concentrations levels utilizing inductively coupled plasma mass spectrometry, and their spatial distribution pattern and pollution quality indices were estimated. Water (45) and fish (7) samples were also analyzed to understand the distribution pattern of PTEs from sediment to water and water to fish. The geostatistical prediction map showed that the concentration range of Cr, Fe, Cu, Co, Zn, Cd, Ni, Pb, and Mn in sampling stations were 27.3-84.1 μg g -1 , 7281-30193 μg g -1 , 50.6-229.7 μg g -1 , 4.8-15.3 μg g -1 , 113.4-776.9 μg g -1 , 10.0-26.9 μg g -1 , 23.8-55.7 μg g -1 , 9.5-39.3 μg g -1 , and 188.6-448.5 μg g -1 respectively. Pollution is alarming in sediment as all of the studied PTEs exceed the threshold effect level according to Sediment Quality Guidelines. Cd levels in sediments were found to be upper than the lowest effect level (LEL), probable effect level (PEL), threshold effect level (TEL), and severe effect level (SEL) for all sample locations. Several pollution assessment indexes (contamination factor, geo-accumulation index, ecological risk index, etc.) also showed that sediment samples were severely polluted by Cd. PTEs status in water and fish is within permissible limits. The study emphasizes that attention should be paid to controlling the excessive accumulation of PTEs in sediment that would further harm the ecological environment and ultimately human health., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We have designed and synthesized red fluorescent mechanically interlocked molecules with dual targeting functionality for live cancer cell specific active targeting followed by selective internalization and imaging of malignant lysosomes along with real-time tracking, 3D, and multicolor cellular imaging applications.

Food samples are routinely screened for food-contaminating beetles (i.e., pantry beetles) due to their adverse impact on the economy, environment, public health and safety. If found, their remains are subsequently analyzed to identify the species responsible for the contamination; each species poses different levels of risk, requiring different regulatory and management steps. At present, this identification is done through manual microscopic examination since each species of beetle has a unique pattern on its elytra (hardened forewing). Our study sought to automate the pattern recognition process through machine learning. Such automation will enable more efficient identification of pantry beetle species and could potentially be scaled up and implemented across various analysis centers in a consistent manner. In our earlier studies, we demonstrated that automated species identification of pantry beetles is feasible through elytral pattern recognition. Due to poor image quality, however, we failed to achieve prediction accuracies of more than 80%. Subsequently, we modified the traditional imaging technique, allowing us to acquire high-quality elytral images. In this study, we explored whether high-quality elytral images can truly achieve near-perfect prediction accuracies for 27 different species of pantry beetles. To test this hypothesis, we developed a convolutional neural network (CNN) model and compared performance between two different image sets for various pantry beetles. Our study indicates improved image quality indeed leads to better prediction accuracy; however, it was not the only requirement for achieving good accuracy. Also required are many high-quality images, especially for species with a high number of variations in their elytral patterns. The current study provided a direction toward achieving our ultimate goal of automated species identification through elytral pattern recognition., Competing Interests: Author CF was employed by company HK3 Lab. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bisgin, Bera, Wu, Ding, Bisgin, Liu, Pava-Ripoll, Barnes, Campbell, Vyas, Furlanello, Tong and Xu.)

Herein, a transition metal-free approach for access to 3,3'-disubstituted peroxyoxindole is disclosed, which harnesses a transient azaoxyallyl cation. This strategy is also applicable to the synthesis of structurally diverse α-peroxycarboxylic acid surrogates. The method exhibits good functional group tolerance and is suitable for generating a library of peroxy-containing compounds.

Probiotics with antimicrobial activity are gaining interest as a topic in the research field. Urinary tract infections (UTIs), acquired in the hospital or the community, are among the most prevalent infections. The emergence of multidrug resistance (MDR) uro-pathogens has made the current situation more critical in terms of global public health. To face this situation, in this study, Lactobacillus fermentum TIU19 (L. fermentum TIU19) was isolated and characterized as a new probiotic strain of the rice-based fermented beverage Haria. Subsequently, we also investigated its application as a biological agent that inhibits the growth of multidrug-resistant uro-pathogens, Escherichia coli, and Enterococcus faecalis . The results showed that, the isolated strain L . fermentum TIU19 was sensitive to all antibiotics tested except vancomycin and was devoid of virulence factors, such as haemolytic and gelatinase activities. Therefore, it may be considered safe for public health. It has many probiotic properties, such as survival in simulated gastrointestinal fluid, antioxidant activity, β-galactosidase producing ability, high cell surface hydrophobicity, adhesion ability to epithelial cells, and strong biofilm producer. The growth inhibitory and antibiofilm activities were shown against two uro-pathogens. All these results suggest that L. fermentum TIU19 can be explored as a potential probiotic with antagonistic activity against MDR uro-pathogenic E. coli and E. faecalis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that would have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Alzheimer's disease, a progressive severe neurodegenerative disorder, has been until now incurable, in spite of serious efforts worldwide. We have designed self-assembled myristoyl-KPGPK lipopeptide-based biocompatible nanovesicles, which can inhibit amyloid fibrillation made by the transmembrane GxxxGxxxGxxxG motif of Aβ-protein and human myelin protein zero as well as reduce their neurotoxicity. Various spectroscopic and microscopic investigations illuminate that the lipopeptide-based nanovesicles dramatically inhibit random coil-to-β-sheet transformation of Aβ 25-37 and human myelin protein zero protein precursor, which is the prerequisite of GxxxGxxxGxxxG motif-mediated fibril formation. Förster resonance energy transfer (FRET) assay using synthesized Cy-3 (FRET donor) and Cy-5 (FRET acceptor)-conjugated Aβ 25-37 also exhibits that nanovesicles strongly inhibit the fibril formation of Aβ 25-37 . The mouse neuro-2a neuroblastoma cell line is used, which revealed the GxxxGxxxGxxxG-mediated cytotoxicity. However, the neurotoxicity has been diminished by co-incubating the GxxxGxxxGxxxG motif with the nanovesicles.

The human transferrin receptor (TFR) is overexpressed in most breast cancers, including preneoplastic ductal carcinoma in situ (DCIS). HB21(Fv)-PE40 is a single-chain immunotoxin (IT) engineered by fusing the variable region of a monoclonal antibody (HB21) against a TFR with a 40 kDa fragment of Pseudomonas exotoxin (PE). In humans, the administration of other TFR-targeted immunotoxins intrathecally led to inflammation and vascular leakage. We proposed that for treatment of DCIS, intraductal (i.duc) injection of HB21(Fv)-PE40 could avoid systemic toxicity while retaining its potent antitumor effects on visible and occult tumors in the entire ductal tree. Pharmacokinetic studies in mice showed that, in contrast to intravenous injection, IT was undetectable by enzyme-linked immunosorbent assay in blood following i.duc injection of up to 3.0 μg HB21(Fv)-PE40. We demonstrated the antitumor efficacy of HB21(Fv)-PE40 in two mammary-in-duct (MIND) models, MCF7 and SUM225, grown in NOD/SCID/gamma mice. Tumors were undetectable by In Vivo Imaging System (IVIS) imaging in intraductally treated mice within 1 wk of initiation of the regimen (IT once weekly/3 wk, 1.5 μg/teat). MCF7 tumor-bearing mice remained tumor free for up to 60 d of observation with i.duc IT, whereas the HB21 antibody alone or intraperitoneal IT treatment had minimal/no antitumor effects. These and similar findings in the SUM225 MIND model were substantiated by analysis of mammary gland whole mounts, histology, and immunohistochemistry for the proteins Ki67, CD31, CD71 (TFR), and Ku80. This study provides a strong preclinical foundation for conducting feasibility and safety trials in patients with stage 0 breast cancer.

Purpose: The study aims to record the quality of life (Qol) and its changes while ovarian cancer (OC) patients undergo debulking surgeries and chemotherapy in a tertiary care hospital of Eastern India., Methods: Patients with advanced epithelial OC (FIGO stages III-IV) were recruited. They underwent primary/interval debulking surgeries with classical chemotherapy (adjuvant/neoadjuvant) of intravenous tri-weekly doses of paclitaxel + carboplatin. QoL was assessed using Fact- O + FACIT-Sp-12 questionnaire with a set of 51 questions in different domains (spiritual, physical, social, emotional, and functional factors) and a special set for OC patients under the heading "Additional concerns." The responses from patients were recorded at baseline (diagnosis/study entry), 2, 4, and 6 months during the treatment visits. Overall survival (OS) was assessed using Kaplan Meier curve., Results: A majority of patients were 49.15±10.8 years of age, school-educated (54%), unemployed/homemakers (73.5%), belonging from rural setup (64.6%) with a monthly income of Rs. 2000/- to Rs. 5000/-. There was no statistically significant (p>0.05) improvement found in Qol from the baseline till the end of the study, neither overall nor in subsets (responders (Rs)/partial responders (PRs)/non-responder (NRs) groups or the adjuvant and neoadjuvant chemotherapy groups). The common toxicities like anemia, constipation, and weight loss were significantly (p<0.05) correlated with the patients' physical, functional, emotional, and social well-being., Conclusion: Ovarian cancer patients represent a poor functional, social, and disease-specific quality of life that needs to be addressed, identified, and improved by the growing nexus of healthcare providers and researchers., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)