Oxidation Analysis of l-Cysteine with a Chiral Sensor Based on Quantum Weak Measurement.

l-Cysteine, distinguished by its possession of reactive sulfhydryl groups within its molecular structure, plays a significant role in both biological systems and the pharmaceutical industry. It stands not only as a natural component integral to the constitution of glutathione but also as the principal precursor for the synthesis of l-cystine through an oxidation reaction. This study endeavors to introduce a novel approach to l-cysteine analysis, capitalizing on its optical activity, whereby an optical rotation detection system grounded in the principles of quantum weak measurement is proffered. The optical rotation angle corresponding to the concentration of chiral solutions can be accurately ascertained through spectral analysis. In practical implementation, a chiral sensing system, boasting a sensitivity of 372 nm/rad, was meticulously constructed, leveraging the concept of weak value amplification. Then, the real-time monitoring of chemical reactions involving l-cysteine and dimethyl sulfoxide was performed. Under the specific experimental conditions outlined in this investigation, it was observed that the oxidation process culminated within approximately 12 h. The application of weak measurement-based chiral sensors holds immense potential, providing robust technical support for real-time monitoring in fields such as chiral analysis and the synthesis of chiral pharmaceutical compounds.

Electronic Modulation in Cu Doped NiCo LDH/NiCo Heterostructure for Highly Efficient Overall Water Splitting.

Layered double hydroxides (LDHs), promising bifunctional electrocatalysts for overall water splitting, are hindered by their poor conductivity and sluggish electrochemical reaction kinetics. Herein, a hierarchical Cu-doped NiCo LDH/NiCo alloy heterostructure with rich oxygen vacancies by electronic modulation is tactfully designed. It extraordinarily effectively drives both the oxygen evolution reaction (151 mV@10 mA cm-2 ) and the hydrogen evolution reaction (73 mV@10 mA cm-2 ) in an alkaline medium. As bifunctional electrodes for overall water splitting, a low cell voltage of 1.51 V at 10 mA cm-2 and remarkable long-term stability for 100 h are achieved. The experimental and theoretical results reveal that Cu doping and NiCo alloy recombination can improve the conductivity and reaction kinetics of NiCo LDH with surface charge redistribution and reduced Gibbs free energy barriers. This work provides a new inspiration for further design and construction of nonprecious metal-based bifunctional electrocatalysts based on electronic structure modulation strategies.

Functional characterization of growth hormone releasing hormone and its receptor in amphioxus with implication for origin of hypothalamic-pituitary axis.

Growth hormone-releasing hormone (GHRH) has been widely shown to stimulate growth hormone (GH) production via binding to GHRH receptor GHRHR in various species of vertebrates, but information regarding the functional roles of GHRH and GHRHR in the protochordate amphioxus remains rather scarce. We showed here that two mature peptides, BjGHRH-1 and BjGHRH-2, encoded by BjGHRH precursor, and a single BjGHRHR protein were identified in the amphioxus Branchiostoma. japonicum. Like the distribution profiles of vertebrate GHRHs and GHRHRs, both the genes Bjghrh and Bjghrhr were widely expressed in the different tissues of amphioxus, including in the cerebral vesicle, Hatschek's pit, neural tube, gill, hepatic caecum, notochord, testis and ovary. Moreover, both BjGHRH-1 and BjGHRH-2 interacted with BjGHRHR, and triggered the cAMP/PKA signal pathway in a dose-dependent manner. Importantly, BjGHRH-1 and BjGHRH-2 were both able to activate the expression of GH-like gene in the cells of Hatschek's pit. These indicate that a functional vertebrate-like GHRH-GHRHR axis had already emerged in amphioxus, which is a seminal innovation making physiological divergence including reproduction, growth, metabolism, stress and osmoregulation possible during the early evolution of vertebrates.

A 9-10-Bit Adjustable and Energy-Efficient Switching Scheme for Successive Approximation Register Analog-to-Digital Converter with One Least Significant Bit Common-Mode Voltage Variation.

A 9-10-bit adjustable and energy-efficient switching scheme for SAR ADC with one-LSB common-mode voltage variation is proposed. Based on capacitor-splitting technology and common-mode conversion techniques, the proposed switching scheme reduces the DAC switching energy by 96.41% compared to the conventional scheme. The low complexity and the one-LSB common-mode voltage offset of this scheme benefit from the simultaneous switching of the reference voltages of the capacitors corresponding to the positive array and the negative array throughout the entire reference voltage switching process, and the reference voltage of each capacitor in the scheme does not change more than two voltages. The post-layout result shows that the ADC achieves the 54.96 dB SNDR, the 61.73 dB SFDR, and the 0.67 µw power consumption with the 10-bit mode and the 48.33 dB SNDR, the 54.17 dB SFDR, and the 0.47 µw power consumption with the 9-bit mode in a 180 nm process with a 100 kS/s sampling frequency.

Conversion of Phosphogypsum into Porous Calcium Silicate Hydrate for the Removal and Recycling of Pb(II) and Cd(II) from Wastewater.

The discharge of lead and cadmium wastewater, along with the pollution caused by phosphogypsum, represents a particularly urgent environmental issue. This study employed a straightforward hydrothermal method to convert phosphogypsum into porous calcium silicate hydrate (P-CSH), which was then used to remove and recover Pb(II) and Cd(II) from wastewater. The adsorption capacities of P-CSH for Pb(II) and Cd(II) were notably high at 989.3 mg/g and 290.3 mg/g, respectively. The adsorption processes adhered to the pseudo-second-order kinetics model and the Langmuir isotherm model. Due to identical adsorption sites on P-CSH for both Pb(II) and Cd(II), competitive interaction occurred when both ions were present simultaneously. Additionally, the adsorption efficacy was minimally impacted by the presence of common coexisting cations in wastewater. The dominant mechanisms for removing Pb(II) and Cd(II) via P-CSH were chemical precipitation and surface complexation. Moreover, the adsorbed heavy metals were efficiently separated and reclaimed from the wastewater through a stepwise desorption process. The primary components of the residue from stepwise desorption were quartz and amorphous SiO2. Following dissolution via pressurized alkaline leaching, this residue could be recycled for synthesizing P-CSH. This research offered a new strategy for the resourceful use of phosphogypsum and heavy metal wastewater.

Is shared decision-making a determinant of polypharmacy in older patients with chronic disease? A cross-sectional study in Hubei Province, China.

BACKGROUND: Shared decision-making(SDM) is recognized as an important means of managing polypharmacy among older people with chronic diseases. However, no studies have quantitatively measured the effect of SDM on polypharmacy. The objective of this study was to compare the impact of SDM and other factors on polypharmacy in inpatients and community patients. Additionally, the study aimed to compare the impact of different decision types on polypharmacy in community patients. METHODS: This is a population-based multicenter retrospective study conducted in Hubei Province, China. A cluster sampling approach was used to recruit 536 chronic disease inpatients from March to April 2019, and 849 community patients were recruited from April to June 2021. Propensity score weighting was used to control the confounding variables and determine the net effect of SDM on polypharmacy. RESULTS: Among the 536 hospitalized patients, the prevalence of polypharmacy was 56.3%. A high level of SDM was significantly associated with a lower risk of polypharmacy. Patients with chronic illnesses aged 76 years and older and with an annual family income of 24,001-36,000 yuan were associated with a lower likelihood of polypharmacy (p < 0.05). Multimorbidity was often accompanied by the occurrence of multiple medication use. Among 849 community patients, the prevalence of polypharmacy was 21.8%. Among types of decision-making, informed and paternalistic decision-making showed a higher likelihood of polypharmacy compared with shared decision-making (P < 0.05). Male, older patients over 76 years of age, urban residents, annual household income of 12,001-24,000 yuan, and multimorbidity were associated with higher likelihood of polypharmacy (P < 0.05). Patients with an annual household income of 24,001-36,000 yuan, 36,001 yuan or more, and good medication compliance showed a lower likelihood of polypharmacy (P < 0.05). CONCLUSIONS: The prevalence of polypharmacy is high among China's older population with chronic disease who should be paid more atthention by the healthcare providers. Additionaly, encouraging the patients' attendance in SDM, reducing paternalistic and informed decision-making during prescribing, improving patient medication compliance, and increasing the promotion and guidance of rational medication use for patients are essential to reduce polypharmacy in Chinese chronic disease patients.

Query-Informed Multi-Agent Motion Prediction.

In a dynamic environment, autonomous driving vehicles require accurate decision-making and trajectory planning. To achieve this, autonomous vehicles need to understand their surrounding environment and predict the behavior and future trajectories of other traffic participants. In recent years, vectorization methods have dominated the field of motion prediction due to their ability to capture complex interactions in traffic scenes. However, existing research using vectorization methods for scene encoding often overlooks important physical information about vehicles, such as speed and heading angle, relying solely on displacement to represent the physical attributes of agents. This approach is insufficient for accurate trajectory prediction models. Additionally, agents' future trajectories can be diverse, such as proceeding straight or making left or right turns at intersections. Therefore, the output of trajectory prediction models should be multimodal to account for these variations. Existing research has used multiple regression heads to output future trajectories and confidence, but the results have been suboptimal. To address these issues, we propose QINET, a method for accurate multimodal trajectory prediction for all agents in a scene. In the scene encoding part, we enhance the feature attributes of agent vehicles to better represent the physical information of agents in the scene. Our scene representation also possesses rotational and spatial invariance. In the decoder part, we use cross-attention and induce the generation of multimodal future trajectories by employing a self-learned query matrix. Experimental results demonstrate that QINET achieves state-of-the-art performance on the Argoverse motion prediction benchmark and is capable of fast multimodal trajectory prediction for multiple agents.

Tumor-suppressive circRHOBTB3 is excreted out of cells via exosome to sustain colorectal cancer cell fitness.

BACKGROUND & AIMS: To clarify the biological roles, circularization process and secretion pathway of circRHOBTB3 in colorectal cancer (CRC) progression. METHODS: We performed a comprehensive analysis of circRNA levels in serum exosomes from multiple types of cancer patients in public databases and verified the higher level of circRHOBTB3 in CRC sera versus healthy donors by RT-qPCR. Then, the function of circRHOBTB3 in CRC was investigated in vitro and in vivo. RNA-seq and RNA pull-down assays together with mass spectrometry identified the downstream signals and the binding proteins of circRHOBTB3. Finally, Antisense oligonucleotides (ASOs) were designed to target circularization and secretion elements of circRHOBTB3 for CRC therapy. RESULTS: circRHOBTB3 levels were increased in the sera but was downregulated in tissue samples in CRC, and the downregulation was associated with poor prognosis. Furthermore, circRHOBTB3 acts a tumor-suppressive circRNA by repressing metabolic pathways, intracellular ROS production in CRC. Several key elements were discovered to regulate circRHOBTB3 circularization and exosomal secretion. Moreover, SNF8 was identified that sorts circRHOBTB3 into exosomes. Interestingly, we found that CRC cells could actively secrete more circRHOBTB3 than normal cells. According to the sequence of regulatory elements for circularization and exosomal secretion, we designed and synthesized ASOs, which increased circRHOBTB3 expression and blocked circRHOBTB3 exosomal secretion. More importantly, ASOs could inhibit CRC growth and metastasis in vitro and in vivo. CONCLUSIONS: circRHOBTB3 plays a tumor-suppressive role in CRC and has to be excreted out of cells to sustain cancer cell fitness. ASOs targeting regulatory elements for circularization and exosomal secretion will become a novel antitumor strategy.

Optical biosensor based on weak value amplification for the high sensitivity detection of Pertuzumab in combination with Trastuzumab binding to the extracellular domain of HER2.

A real-time optical phase sensing scheme based on weak value amplification was proposed to monitor the especially binding process of Pertuzumab combined with Trastuzumab on HER2 positive cells. From the wavelength shift of output spectrum, the phase difference between measuring and referential path related to the concentration of Pertuzumab as well as Trastuzumab could be calculated. With this approach, the limit of detection (LOD) of 5.54 × 10-13 M for Pertuzumab assay was achieved. Besides, the kinetics signal of Pertuzumab in combination with Trastuzumab binding to HER2 was detected in real time. Experimental results demonstrated that both Trastuzumab and Pertuzumab can be captured by HER2, but the former was significantly superior to the latter in terms of the target number. Additionally, the binding speed was analyzed and demonstrated to be closely correlated with the initial concentration of the targeting agents.

Dual-targeting nanozyme for tumor activatable photo-chemodynamic theranostics.

Tumor phototheranostics holds a great promise on account of its high spatiotemporal resolution, tumor-specificity, and noninvasiveness. However, physical limitation of light penetration and "always on" properties of conventional photothermal-conversion agents usually cause difficulty in accurate diagnosis and completely elimination of tumor. Meanwhile, nanozymes mediated Fenton reactions can well utilize the tumor microenvironment (TME) to generate hydroxyl radicals for chemodynamic therapy (CDT), but limited by the concentration of H2O2 in TME and the delivery efficiency of nanozymes. To overcome these problems, a dual-targeting nanozyme (FTRNPs) is developed for tumor-specific in situ theranostics, based upon the assembling of ultrasmall Fe3O4 nanoparticles, 3,3',5,5'-tetrameth-ylbenzidine (TMB) and the RGD peptide. The FTRNPs after H2O2 treatment exhibits superior photothermal stability and high photothermal conversion efficiency (η = 50.9%). FTRNPs shows extraordinary accumulation and retention in the tumor site by biological/physical dual-targeting, which is 3.54-fold higher than that without active targeting. Cascade-dual-response to TME for nanozymes mediated Fenton reactions and TMB oxidation further improves the accuracy of both photoacoustic imaging and photothermal therapy (PTT). The tumor inhibition rate of photo-chemodynamic therapy is ~ 97.76%, which is ~ 4-fold higher than that of PTT or CDT only. Thus, the combination of CDT and PTT to construct "turn on" nanoplatform is of great significance to overcome their respective limitations. Considering its optimized "all-in-one" performance, this new nanoplatform is expected to provide an advanced theranostic strategy for the future treatment of cancers.

Methyl CpG binding protein 2 promotes colorectal cancer metastasis by regulating N6 -methyladenosine methylation through methyltransferase-like 14.

RNA N6 -methyladenosine (m6 A) is an emerging regulatory mechanism for tumor progression in several types of cancer. However, the underlying regulation mechanisms of m6 A methylation in colorectal cancer (CRC) remain unknown. Although the oncogenic function of methyl CpG binding protein 2 (MeCP2) has been reported, it is still unclear whether MeCP2 could alter RNA m6 A methylation state. Here, we systematically identified MeCP2 as a prometastasis gene to regulate m6 A methylation in CRC. Interestingly, MeCP2 could bind to methyltransferase-like 14 (METTL14) to coregulate tumor suppressor Kruppel-like factor 4 (KLF4) expression through changing m6 A methylation modification. Furthermore, insulin-like growth factor 2 mRNA-binding protein 2 recognized the unique modified m6 A methylation sites to enhance KLF4 mRNA stability. Taken together, these findings highlight the novel function of MeCP2 for regulating m6 A methylation and reveal the underlying molecular mechanism for the interaction between MeCP2 and METTL14, which offers a better understanding of CRC progression and metastasis.

Distinct roles of programmed death ligand 1 alternative splicing isoforms in colorectal cancer.

Although anti-programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has achieved great success in some cancers, most colorectal cancer (CRC) patients remain unresponsive. Therefore, further clarification of the underlying mechanisms is needed to improve the therapy. In this study, we explored the distinct functions of different PD-L1 alternative splicing isoforms in CRC. We investigated the biological functions in PD-L1 knocked down/knockout cells, which were verified through overexpression of PD-L1 isoforms a, b, and c. The roles of PD-L1 isoforms in immune surveillance resistance was also analyzed. Meanwhile, we performed RNA-seq to screen the downstream molecules regulated by PD-L1 isoforms. Finally, we detected PD-L1 and PD-L1 isoforms levels in a cohort of serum samples, two cohorts of CRC tissue samples, and analyzed the correlation of PD-L1 isoforms with PD-1 blockade therapy response in two clinical CRC cases. The results indicated that PD-L1 knockout inhibited proliferation, migration, and invasion, and isoform b exerted a more significant inhibitory effect on T cells than the other two isoforms. Moreover, isoform c could promote CRC progression through regulating epithelial-mesenchymal transition. Clinical data showed that CRC patients with positive PD-L1 expression were associated with poorer overall survival. High serum PD-L1 level was associated with poor prognosis. The level of isoform b or c was negatively associated with prognosis, and a higher level of isoform b was associated with a good response to anti-PD-1 therapy. In conclusion, isoform b should be considered as a biomarker for clinical responsiveness to anti-PD-1/PD-L1 immunotherapy; isoform c had a prometastatic role and is a new potential target for CRC therapy.

Genome mining of secondary metabolites from a marine-derived Aspergillus terreus B12.

Owing to the prominent capabilities of bioconversion and biosynthesis, A. terreus has become attractive in biotechnical and pharmaceutical industry. In this work, an Aspergillus strain with potential antibacterial activities, was isolated from sponge in South China Sea. Based on the morphological and phylogenetic analysis, the strain was identified as A. terreus B12. Via the Illumina MiSeq sequencing platform, the complete genome was obtained, showing a genetic richness of biosynthetic gene clusters (BGCs), which might underpin the metabolic plasticity and adaptive resilience for the strain. Genome mining identified 67 BGCs, among which, 6 gene clusters could allocate to known BGCs (100% identity), corresponding to diverse metabolites like clavaric acid, dihydroisoflavipucine/isoflavipucine, dimethylcoprogen, alternariol, aspterric acid, and pyranonigrin E. Moreover, a range of compounds was isolated from B12 fermentation, e.g., terrein, butyrolactone I, terretonin A&E, acoapetaline B, and epi-aszonalenins A. Of note, acoapetaline B and epi-aszonalenins A, which had been respectively reported in plants and A. novofumigatus but with scarce information, was unexpectedly obtained from this species for the first time. The genomic and metabolic heterogeneity observed in strain B12, should be at least partially attributed to the genetic variability and biochemical diversity of A. terreus, which could be an interesting issue open to future efforts.

Amphioxus ribosomal proteins RPS15, RPS18, RPS19 and RPS30-precursor act as immune effectors via killing or agglutinating bacteria.

Previous studies show that some ribosomal proteins perform immune effector functions via killing bacteria directly. However, it remains largely unknown about other effector functions of ribosomal proteins during a bacterial infection. In this study, we expressed and purified four ribosomal proteins of the amphioxus Branchiostoma japonicum, termed rBjRPS15, rBjRPS18, rBjRPS19 and rBjRPS30-precursor (rBjRPS30P). They all exhibited bactericidal activity against Gram-positive Staphylococcus aureus, and with the exception of rBjRPS19 and rBjRPS30P, were capable of killing Gram-negative Escherichia coli. Importantly, rBjRPS15, rBjRPS19 and rBjRPS30P were able to agglutinate S. aureus in the presence of Mg2+, but none of them could agglutinate E. coli even in the presence of Mg2+ or Ca2+. Moreover, the S. aureus agglutination was achieved by the binding of these three proteins to the peptidoglycan component of the bacterial cell wall. This is the first report showing that some ribosomal proteins possess bacterial agglutinating activity, and these data provide a new angle to the roles of ribosomal proteins in immune defense.

Optimal rare-earth (La, Y and Sm) doping conditions and enhanced mechanism for photocatalytic application of ceria nanorods.

Morphological tuning or additional cation doping is one of the potential and simple methods to enhance the photocatalytic properties of ceria, in which rare-earth element doped ceria nanorods (CeO2-RE NRs) are expected to be a promising photocatalyst with high activity. But the optimal doping conditions, including the variety and concentration of RE elements are ambiguous, and the contribution of doped RE ions to the enhancement of photocatalytic activity needs to be further studied. In this work, we doped La, Y and Sm with a wide range of 0%-30% into CeO2 NRs, and investigated the phase, morphology, band gap, oxygen vacancy concentration, PL spectra and photocatalytic activity variation under different doping conditions. All synthesized CeO2-RE NRs possessed a good nanorod morphology except the 15 and 30% Y-doped samples. The energy band gaps of the synthesized samples changed slightly; the 10% CeO2-RE NRs with the narrowest band gaps possessed the higher photocatalytic performance. The most outstanding photocatalyst was found to be the 10% Y-doped CeO2 NRs with a methylene blue photodegradation ratio of 85.59% and rate constant of 0.0134 min-1, which is particularly associated with a significant higher oxygen vacancy concentration and obviously lower recombination rate of photogenerated e-/h+ pairs. The doped RE ions and the promotion of oxygen vacancy generation impede the recombination of photogenerated carriers, which is proposed as the main reason to enhance the photocatalytic property of CeO2.

p38-regulated FOXC1 stability is required for colorectal cancer metastasis.

Aberrant expression of forkhead box C1 (FOXC1) promotes tumor metastasis in multiple human malignant tumors. However, the upstream modulating mode and downstream molecular mechanism of FOXC1 in metastasis of colorectal cancer (CRC) remain unclear. Herein we describe a systematic analysis of FOXC1 expression and prognosis in CRC performed on our clinical data and public databases, which indicated that FOXC1 upregulation in CRC samples was significantly associated with poor prognosis. FOXC1 knockdown inhibited migration and invasion, whereas FOXC1 overexpression caused the opposite phenotype in vitro and in vivo. Furthermore, MMP10, SOX4 and SOX13 were verified as the target genes of FOXC1 for promoting CRC metastasis. MMP10 was demonstrated as the direct target and mediator of FOXC1. Interestingly, Ser241 and Ser272 of FOXC1 were identified as the key sites to interact with p38 and phosphorylation, which were critically required for maintaining the stability of FOXC1 protein. Moreover, FOXC1 was dephosphorylated by protein phosphatase 2A and phosphorylated by p38, which maintained FOXC1 protein stability through inhibiting ubiquitination. Expression of p38 was correlated with FOXC1 and MMP10 expression, indirectly indicating that FOXC1 was regulated by p38 MAPK. Therefore, FOXC1 is strongly suggested as a pro-metastatic gene in CRC by transcriptionally activating MMP10, SOX4 and SOX13; p38 interacts with and phosphorylates the Ser241 and ser272 sites of FOXC1 to maintain its stability by inhibiting ubiquitination and degradation. In conclusion, the protein stability of FOXC1 mediated by p38 contributes to the metastatic effect in CRC. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Investigation on the control of inclusions and tensile strength in Ce-treated P110-grade oil casing steel.

This research added rare Earth elements Ce to the P110-grade oil casing steel to reveal their influence on the inclusions and tensile properties. The content of cerium in the steel varied from 0 to 452 ppm. Based on the classical thermodynamic calculation, the predominance diagram of Re-containing inclusions in P110-grade steel was obtained. The evolution route of the inclusions composition with the increasing cerium content in the steel was xCaO⋅yAl2O3 → Al2O3-CeAlO3 → Ce2O3-CeAlO3 → Ce2O3-Ce2O2S → Ce2O2S, which agreed well with the thermodynamic analysis. As the cerium content at 235 ppm, the size of Ce containing inclusions has a minimal size at 2.82 µm. Suitable Ce content can modify the big-size xCaO⋅yAl2O3 inclusions into small-size Re-containing inclusions. The results demonstrate that the tensile performance of this steel can be improved as the cerium content increases from 0 to 235 ppm. However, once the cerium content exceeds 235 ppm, further increases in cerium content led to a decline in performance. The experimental results shows that the presence of large-sized Ce2O2S inclusions and the change of microstructure, will lead to the decrease in tensile performance.

Profiling the interplay and coevolution of Microcystis aeruginosa and cyanosiphophage Mic1.

The cyanosiphophage Mic1 specifically infects the bloom-forming Microcystis aeruginosa FACHB 1339 from Lake Chaohu, China. Previous genomic analysis showed that its 92,627 bp double-stranded DNA genome consists of 98 putative open reading frames, 63% of which are of unknown function. Here, we investigated the transcriptome dynamics of Mic1 and its host using RNA sequencing. In the early, middle, and late phases of the 10 h lytic cycle, the Mic1 genes are sequentially expressed and could be further temporally grouped into two distinct clusters in each phase. Notably, six early genes, including gp49 that encodes a TnpB-like transposase, immediately reach the highest transcriptional level in half an hour, representing a pioneer cluster that rapidly regulates and redirects host metabolism toward the phage. An in-depth analysis of the host transcriptomic profile in response to Mic1 infection revealed significant upregulation of a polyketide synthase pathway and a type III-B CRISPR system, accompanied by moderate downregulation of the photosynthesis and key metabolism pathways. The constant increase of phage transcripts and relatively low replacement rate over the host transcripts indicated that Mic1 utilizes a unique strategy to gradually take over a small portion of host metabolism pathways after infection. In addition, genomic analysis of a less-infective Mic1 and a Mic1-resistant host strain further confirmed their dynamic interplay and coevolution via the frequent horizontal gene transfer. These findings provide insights into the mutual benefit and symbiosis of the highly polymorphic cyanobacteria M. aeruginosa and cyanophages. IMPORTANCE: The highly polymorphic Microcystis aeruginosa is one of the predominant bloom-forming cyanobacteria in eutrophic freshwater bodies and is infected by diverse and abundant cyanophages. The presence of a large number of defense systems in M. aeruginosa genome suggests a dynamic interplay and coevolution with the cyanophages. In this study, we investigated the temporal gene expression pattern of Mic1 after infection and the corresponding transcriptional responses of its host. Moreover, the identification of a less-infective Mic1 and a Mic1-resistant host strain provided the evolved genes in the phage-host coevolution during the multiple-generation cultivation in the laboratory. Our findings enrich the knowledge on the interplay and coevolution of M. aeruginosa and its cyanophages and lay the foundation for the future application of cyanophage as a potential eco-friendly and bio-safe agent in controlling the succession of harmful cyanobacterial blooms.

miR-277 targets the proapoptotic gene-hid to ameliorate Aß42-mediated neurodegeneration in Alzheimer's model.

Alzheimer's disease (AD), an age-related progressive neurodegenerative disorder, exhibits reduced cognitive function with no cure to date. One of the reasons for AD is the accumulation of Amyloid-beta 42 (Aß42) plaque(s) that trigger aberrant gene expression and signaling, which results in neuronal cell death by an unknown mechanism(s). Misexpression of human Aß42 in the developing retina of Drosophila exhibits AD-like neuropathology. Small non-coding RNAs, microRNAs (miRNAs), post-transcriptionally regulate the expression of their target genes and thereby regulate different signaling pathways. In a forward genetic screen, we identified miR-277 (human ortholog is hsa-miR-3660) as a genetic modifier of Aß42-mediated neurodegeneration. Loss-of-function of miR-277 enhances the Aß42-mediated neurodegeneration. Whereas gain-of-function of miR-277 in the GMR > Aß42 background downregulates cell death to maintain the number of neurons and thereby restores the retinal axonal targeting defects indicating the functional rescue. In addition, gain-of-function of miR-277 rescues the eclosion- and climbing assays defects observed in GMR > Aß42 background. Thus, gain-of-function of miR-277 rescues both structurally as well as functionally the Aß42-mediated neurodegeneration. Furthermore, we identified head involution defective (hid), an evolutionarily conserved proapoptotic gene, as one of the targets of miR-277 and validated these results using luciferase- and qPCR -assays. In the GMR > Aß42 background, the gain-of-function of miR-277 results in the reduction of hid transcript levels to one-third of its levels as compared to GMR > Aß42 background alone. Here, we provide a novel molecular mechanism where miR-277 targets and downregulates proapoptotic gene, hid, transcript levels to rescue Aß42-mediated neurodegeneration by blocking cell death. These studies shed light on molecular mechanism(s) that mediate cell death response following Aß42 accumulation seen in neurodegenerative disorders in humans and provide new therapeutic targets for neurodegeneration.

Optical biosensor based on weak measurement for ultra-sensitive detection of calreticulin in human serum.

A novel real-time optical phase sensing method based on the Mach-Zehnder interference principle has been proposed for the detection of calreticulin (CRT) levels in human serum samples. In this approach, anti-CRT antibodies are utilized to capture CRT molecules in serum, leading to a phase shift in both the measuring and reference arms of the system. By employing the concept of weak amplification within the framework of weak measurements, it becomes feasible to continuously monitor the response of CRT in real-time, allowing for the precise determination of serum CRT content at the picomolar level. Our achievement may pave the way in establishing CRT as a diagnostic biomarker for a wide range of medical applications, including rheumatoid arthritis.