Biocompatibility FeOOH QD@ATP-BODIPY nanocomposite for glutathione detection and intracellular imaging.

Monitoring of glutathione has attracted considerable attention owing to its biological and clinical significance. An eco-friendly, economic, simple, biocompatible probe with excellent sensitivity and selectivity is very important. Herein, FeOOH QD@ATP-BODIPY nanocomposite was fabricated from one-step synthesized FeOOH quantum dots (FeOOH QD) and commercial boron-dipyrromethene-conjugated adenosine 5'-triphosphate (ATP-BODIPY) for glutathione (GSH) sensing in solutions and living cells. Three fascinate merits of FeOOH QD were confirmed: (a) as fluorescence quencher for ATP-BODIPY, (b) as selective recognizer of GSH and (c) with carrier effects and membrane permeability. The construction and response mechanism of the nanocomposite was based on the competitive coordination chemistry and redox reaction of FeOOH QD between GSH and phosphate group of ATP-BODIPY. Under the optimal conditions, the detection limit for GSH was as low as 68.8 nM. Excellent linear range of 0.2-400 µM was obtained. Furthermore, the chemical response of the nanocomposite exhibits high selectivity toward GSH over other electrolytes and biomolecules. It was successfully applied for GSH determination in human serum samples. The MTT assay exhibited FeOOH QD@ATP-BODIPY nanocomposite own good biocompatibility. FeOOH QD@ATP-BODIPY respond to GSH in living cells in situ was also proved via fluorescence imaging. These suggested that the FeOOH QD@ATP-BODIPY nanocomposite had potential application in biological and clinical applications.

Tris-assisted one-step fabrication of functional carbon dots for specific folate receptor positive-expressed cancer cell imaging.

Specific staining of cancer cells is momentous for cancer research. Nanoprobe with multivalent recognition is emerging as powerful tools for bioimaging, but the nonspecific cell uptake and complex functional modification procedures are still obstacles for specific detection and convenient synthesis. Carbon dots (CDs) with an intrinsic targeting ability, excellent optical properties and biocompatibility acquired from an efficient one-step fabrication procedure were urgently desired in specific cancer cells visualization. Herein, inspired by the interrelationships between interface and biomolecular mechanisms, we suggested that it was possible to construct CDs with the desired characteristics for folate receptor (FR) positive-expressed cancer cell imaging via rich hydroxyl groups Tris-assisted one-step hydrothermal treatment of folate acid (FA) and l-Arginine (L-Arg) precursors. The prepared small-sized F-CDs were equipped with abundant hydroxyl, pterin and negative charge surface, and possessed environmental friendliness, outstanding photostability and biocompatibility. Moreover, F-CDs had an intrinsic FR positive-expressed cancer cell targeting ability without any post-modification of the ligands. Rich hydroxyl groups play a vital role in endowing the optical properties and biological effects of F-CDs. F-CDs could be used as a promising candidate for FR-expressed cancer cell labeling and tracking. In addition, the caveolae-mediated endocytosis pathway of F-CDs was ascertained. More importantly, experimental results confirmed that the combination of physicochemical properties may provide an efficient strategy to overcome non-specific cell uptake interactions for cell labeling. Our strategy put forward a promising alternative to design fluorescent CDs for extensive chemical and biomedical applications.

Simultaneous Detection of Aldehyde Metabolites by Light-Assisted Ambient Ionization Mass Spectrometry.

In the clinic, small-molecule metabolites (SMMs) in blood are highly convincing indicators for disease diagnosis, such as cancer. However, challenges still exist for detection of SMMs due to their low concentration and complicated components in blood. In this work, we report the design of a novel "selenium signature" nanoprobe (Se nanoprobe) for efficient identification of multiple aldehyde metabolites in blood. This Se nanoprobe consists of magnetic nanoparticles that can enrich aldehyde metabolites from a complex environment, functionalized with photosensitive "selenium signature" hydrazide molecules that can react with aldehyde metabolites. Upon irradiation with UV, the aldehyde derivatives can be released from the Se nanoprobe and further sprayed by mass spectrometry through ambient ionization (AIMS). By quantifying the selenium isotope distribution (MS/MS) from the derivatization product, accurate detection of several aldehyde metabolites, including valeraldehyde (Val), heptaldehyde (Hep), 2-furaldehyde (2-Fur), 10-undecenal aldehyde (10-Und), and benzaldehyde (Ben), is realized. This strategy reveals a new solution for quick and accurate cancer diagnosis in the clinic.

The lncRNA LINC00339-encoded peptide promotes trophoblast adhesion to endometrial cells via MAPK and PI3K-Akt signaling pathways.

BACKGROUND: Endometrial receptivity (ER), a pivotal event for successful embryo implantation, refers to the capacity of endometrium to allow the adhesion of the trophectoderm of the blastocyst to endometrial cells. In this paper, we set to elucidate whether the peptides encoded by lncRNAs could influence trophoblast cells' adhesion to endometrial cells. METHODS: WGCNA construction and bioinformatics were used to find out the ER-related lncRNAs with coding potential. Protein analysis was done by immunoblotting and immunofluorescence (IF) microscopy. CCK-8 and Calcein-AM/PI double staining assays were employed to evaluate cell viability. The effect of the peptide on trophoblast spheroids' adhesion to endometrial cells was evaluated. The RNA sequencing (RNA-seq) analysis was applied to identify downstream molecular processes. RESULTS: lncRNA LINC00339 was found to be related to ER development and it had been predicted to have protein-coding potential. LINC00339 had high occupancy of ribosomes and was confirmed to encode a 49-aa peptide (named LINC00339-205-49aa). LINC00339-205-49aa could promote the attachment of JAR trophoblast spheroids to Ishikawa endometrial cells in vitro. LINC00339-205-49aa also upregulated the expression of E-cadherin in Ishikawa cells. Mechanistically, MAPK and PI3K-Akt signaling pathways were involved in the modulation of LINC00339-205-49aa, which were activated by LINC00339-205-49aa in Ishikawa cells. CONCLUSION: These data demonstrate that a previously uncharacterized peptide encoded by lncRNA LINC00339 has the ability to enhance JAR trophoblast spheroids' adhesion to Ishikawa endometrial cells, highlighting a new opportunity for the development of drugs to improve ER.

Identification of sulfhydryl-containing proteins and further evaluation of the selenium-tagged redox homeostasis-regulating proteins.

Chemoproteomic profiling of sulfhydryl-containing proteins has consistently been an attractive research hotspot. However, there remains a dearth of probes that are specifically designed for sulfhydryl-containing proteins, possessing sufficient reactivity, specificity, distinctive isotopic signature, as well as efficient labeling and evaluation capabilities for proteins implicated in the regulation of redox homeostasis. Here, the specific selenium-containing probes (Se-probes) in this work displayed high specificity and reactivity toward cysteine thiols on small molecules, peptides and purified proteins and showed very good competitive effect of proteins labeling in gel-ABPP. We identified more than 6000 candidate proteins. In TOP-ABPP, we investigated the peptide labeled by Se-probes, which revealed a distinct isotopic envelope pattern of selenium in both the primary and secondary mass spectra. This unique pattern can provide compelling evidence for identifying redox regulatory proteins and other target peptides. Furthermore, our examiation of post-translational modification (PTMs) of the cysteine site residues showed that oxidation PTMs was predominantly observed. We anticipate that Se-probes will enable broader and deeper proteome-wide profiling of sulfhydryl-containing proteins, provide an ideal tool for focusing on proteins that regulate redox homeostasis and advance the development of innovative selenium-based pharmaceuticals.

Anterior chamber cytokine production and postoperative macular edema in patients with diabetes undergoing FLACS.

PURPOSE: To evaluate the effect of femtosecond laser-assisted cataract surgery (FLACS) and manual cataract surgery (MCS) on proinflammatory cytokine expression in patients with diabetes vs nondiabetic patients. SETTING: Outpatient surgical center in Vaughan, Ontario, Canada. DESIGN: Prospective cohort study. METHODS: Patients with diabetes and nondiabetic patients undergoing noncomplicated MCS or FLACS were assigned into 4 cohorts: MCS nondiabetic (n = 30), FLACS nondiabetic (n = 42), MCS diabetic (n = 40), and FLACS diabetic (n = 40). Aqueous humor inflammatory mediator concentrations were evaluated at MCS onset and after femtosecond laser treatment. The presence of cystoid macular edema, anterior chamber (AC) inflammation, central retinal thickness, macular volume, and retinal microvascular changes (through optical coherence tomography angiography) were evaluated preoperatively and on postoperative day 1, week 1, month 1 (POM1), and month 3 (POM3). RESULTS: Patients with diabetes receiving FLACS had a higher concentration of interleukin (IL)-7, IL-13, and interferon-induced protein-10 than MCS diabetic patients; they also demonstrated higher levels of vascular endothelial growth factor and lower levels of interferon (IFN)-γ, granulocyte colony-stimulating factor, and IFN-α2 compared with MCS nondiabetic patients. Macular volume appeared to be significantly higher in MCS diabetic vs MCS non-diabetic patients at POM1 and between FLACS diabetic vs FLACS nondiabetic patients at POM3. There were no other significant differences between the cohorts for any parameter. CONCLUSIONS: FLACS use in patients with diabetes demonstrated some differences in AC cytokine expression compared with non-diabetic FLACS or diabetic patients undergoing MCS; however, there was no increase in clinical inflammatory biomarkers. FLACS seems to be a safe technique to use in patients with diabetes.

Pt-Se-Bonded Nanoprobe for High-Fidelity Detection of Non-small Cell Lung Cancer and Enhancement of NIR II Photothermal Therapy.

Non-small cell lung cancer (NSCLC) accounts for a high proportion of lung cancer cases globally, but early detection remains challenging, and insufficient oxygen supply at tumor sites leads to suboptimal treatment outcomes. Therefore, the development of core-shell Au@Pt-Se nanoprobes (Au@Pt-Se NPs) with peptide chains linked through Pt-Se bonds was designed and synthesized for NSCLC biomarker protein calcium-activated neutral protease 2 (CAPN2) and photothermal therapy (PTT) enhancement. The NP can be specifically cleaved by CAPN2, resulting in fluorescence recovery to realize the detection. The Pt-Se bonds exhibit excellent resistance to biologically abundant thiols such as glutathione, thus avoiding "false-positive" results and enabling precise detection of NSCLC. Additionally, the platinum (Pt) shell possesses catalase-like properties that catalyze the generation of oxygen from endogenous hydrogen peroxide within the tumor, thereby reducing hypoxia-inducible factor-1α (HIF-1α) levels and alleviating the hypoxic environment at the tumor site. The Au@Pt-Se NPs exhibit strong absorption bands, enabling the possibility of PTT in the near-infrared II region (NIR II). This study presents an effective approach for the early detection of NSCLC while also serving as an oxygen supplier to alleviate the hypoxic environment and enhance NIR II PTT.

Highly sensitive quantification of ultratrace As(V) via iEESI-MS.

Arsenate (As(V)) is a fatal poison and is widely distributed in the environment. The quick and accurate determination of As(V) is of great importance. Herein, we developed a novel competitive coordination strategy for the quantification of ultratrace As(V) using online internal extractive electrospray ionization mass spectrometry (iEESI-MS). Our strategy demonstrates great success for direct ultratrace As(V) detection in broad types of samples, from solids to liquids, such as food, water and biological samples.

Detection of Cysteine Sulfenic Acid on E. coli Proteins with a Biotin-Benzoboroxole Probe.

S-sulfenylation of cysteine residues on proteins can effectively change protein structures and accordingly regulate their functions in vivo. Investigation of S-sulfenylation in different biological environments is thus vital for a systematic understanding of cellular redox regulation. In this work, a functional probe, biotin-benzoboroxole (Bio-ben), was designed for the detection of cysteine sulfenic acid (Cys-SOH). The performance of Bio-ben was characterized by small-molecule sulfenic acid, protein models, and proteome tests via mass spectra and western blotting. The results showed that Bio-ben was validated for cysteine sulfenic acid on proteins with good capture efficiency even at low concentrations. Compared with commonly used probes such as dimedone, the current probe has significantly shortened labeling time and exhibited comparable sensitivity. The proposed method provides a new approach for exploring S-sulfenylation in the oxidative modification of proteins and is helpful for related biological and clinical applications.

Anti-LGI1 encephalitis with initiating symptom of seizures in children.

Background: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is infrequently reported but more and more recognizable in children. Here we give detailed description of the clinical features and long-term outcome of three cases of childhood onset anti-LGI1 encephalitis. Methods: Three anti-LGI1 encephalitis patients were hospitalized in the Department of Pediatrics at Qilu Hospital of Shandong University. Data about the clinical manifestations, treatments and long-term follow-up outcomes were described in detail. Results: Case 1 showed an adolescent girl with initiating symptom of acute-onset frequent focal seizures. Her serum LGI1-antibody test was positive, and she had a good response to antiseizure medication (ASM) and IVIG. Case 2 showed a preschool-age boy with long-period refractory focal seizures and recent behavioral change. Both serum and cerebrospinal fluid (CSF) tests of LGI1-antibody were positive, and the MRI showed progressive atrophy in the left hemisphere. The symptoms got improved after receiving second-line immunotherapy initially but there are still the sequelae of drug-resistant epilepsy and mild to moderate intellectual disability. Case 3 showed an adolescent boy with initiating symptom of acute-onset frequent focal seizures. Both serum and CSF tests of LGI1-antibody were positive, and he had a good response to immunotherapy. By analyzing all literature-reported 19 pediatric cases, we found pediatric anti-LGI1 encephalitis is more common in female and adolescent. Seizures and behavioral changes were the most common symptoms. CSF pleocytosis and LGI1-antibodies results were mostly negative. Most patients showed good response to immunotherapy. Conclusion: Childhood onset anti-LGI1 encephalitis is a heterogeneous clinical syndrome, ranging from typical limbic encephalitis to isolating focal seizures. It is important to test autoimmune antibodies when encountering similar cases and repeat antibody testing if necessary. Timely recognition leads to earlier diagnosis and more rapid initiation of effective immunotherapy and potentially better outcomes.

The Epitope Basis of Embryonic Stem Cell-Induced Antitumor Immunity against Bladder Cancer.

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) share many cellular and molecular features with cancer cells. Taking advantage of these similarities, stem cells are effective vaccines against cancers in animal models. However, the molecular basis is not well understood, which hinders the development of effective cancer vaccines. Here, prophylactic and therapeutic bladder cancer vaccines composed of allogeneic ESCs and CpG with or without granulocyte macrophage colony stimulating factor are tested. The ESC-based cancer vaccines are able to induce specific antitumor immunity including stimulating cytotoxic CD8+ T cells and memory CD4+ T cells, reducing myeloid-derived suppressor cells, and preventing bladder cancer growth in mouse models. Furthermore, several genes that are overexpressed in both ESCs and tumors are identified. An epitope-based vaccine designed with shared overexpressed proteins induces specific antitumor immunity and reduces bladder cancer growth. Functional epitopes underlying the action of stem cell-based vaccines against bladder cancer are identified and it is confirmed that ESC-based anticancer vaccines have great potential. A systematic approach is provided here to developing novel effective epitope-based cancer vaccines in the future.

Argentinian flag sign during refractive laser-assisted cataract surgery - A case report.

Purpose: The Argentinian flag sign, or radial capsular tear extensions, is a rare complication when performing capsulorhexis during cataract surgery. Identifying and managing this complication early is important to prevent the tear from propagating around the periphery leading to posterior capsular rupture or vitreous loss. Observations: The Argentinian flag sign was previously reported in a case of femtosecond laser-assisted cataract surgery (FLACS). However, our report presents the first case after FLACS using the Catalys™ Precision Laser System, a platform which has been associated with a larger percentage of complete capsulotomies when compared to other platforms. Radial extensions of the capsular tear were observed in a 27-year-old male patient with an intumescent cataract in left eye. The complication was managed by manually redirecting and completing the radial extension flaps, along with delicate phacoemulsification and manual cutting of capsular edge in areas with significant capsular-IOL overlap. Conclusions and importance: Our case report highlights that despite the Catalys™ Precision Laser System success rates, radial tears may occur, especially in highly pressurized intumescent cataract. Therefore, surgeons must be prepared to optimize the surgical techniques to prevent the occurrence of this complication, as well as identify and manage it when it presents.

Complete chloroplast genome and phylogenetic analysis of Meliosma oldhamii Miq. ex Maxim. (Sabiaceae).

Meliosma oldhamii Miq. is a deciduous arbor and a member of Sabiaceae. It is one of the rare and protected plants with outstanding ornamental and economic value in Jiangsu, China. In addition to the resource values indicated above, there are numerous other elements that require additional research, including the chloroplast (cp) genomic information. In this work, the complete cp genome sequence of M. oldhamii was assembled and characterized for the first time. The complete cp genome of M. oldhamii was 159,950 base pair (bp) in length, including a large single-copy (LSC) region of 87,147 bp, a small single-copy (SSC) region of 18,015 bp, and the inverted repeats (IRs) region of 27,394 bp. It contains 131 genes, including 37 tRNA genes, eight rRNA genes, 85 protein-coding genes, and one pseudogene. The overall GC content of M. oldhamii cp genome was 37.95%. The placement of M. oldhamii in the phylogenetic tree constructed using the complete cp genome is largely congruent with previous studies. The clustering of Meliosma is non-monophyletic, aligns more closely with existing morphological taxonomic studies, thereby enhancing the scholarly and scientific nature of this research.

The complete chloroplast genome sequence of Thunbergia erecta (Benth.) T. Anders. (Acanthaceae).

Thunbergia erecta (Benth.) T. Anders. is an upright shrub species of Acanthaceae with great ecological and economical values. In this paper, we explored the complete chloroplast genome sequence of T. erecta using next generation sequencing to provide genomic resources that could help to promote its conservation. The genome of T. erecta is 152,202 bp in length, containing a large single-copy region of 84,232 bp, and a small single-copy region of 17,656 bp. It encodes a total of 131 genes, including 8 rRNA genes, 37 tRNA genes, 84 protein-coding genes and 2 pseudo genes. The GC content of T. erecta genome is 38.47%. The phylogenetic analysis suggests that it was closely related to Avicennia marina in Acanthaceae. In addition, we found that T. erecta appeared late clade in the whole family while outgroups plants appeared even later. T. erecta is morphologically similar to other plants in Acanthaceae, but is genetically closed to the outgroup species.

Diabetic kidney disease treatment: new perspectives.

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage kidney disease worldwide, as the obesity epidemic and the burden of diabetes continue to rise globally. In general, guideline management of patients with DKD recommends lifestyle modifications, blood pressure and glycemic control, and dyslipidemia treatment along with other cardiovascular disease risk reduction measures. The inhibition of the renin-angiotensin system (RAS) using an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker remains the foundational therapy for DKD. In type 2 diabetes (T2D), significant advances in therapeutics, including the sodium-glucose cotransporter-2 inhibitors (SGLT2i), the glucagon-like peptide-1 receptor agonists (GLP-1 RA), and the nonsteroidal mineralocorticoid receptor agonist (MRA) finerenone, have dramatically expanded the armamentarium for treating DKD and its cardiovascular complications. Initiating, optimizing, and sustaining evidence-based pharmacological therapy using a therapeutic combination of RAS inhibitor + SGLT2i/GLP-1 RA + nonsteroidal MRA + statin is likely to significantly improve outcomes for T2D with DKD. Research into potential novel therapeutic targets for DKD remains particularly active and brings much anticipation and optimism to this field.

Tandem strategy of photocatalytic preoxidation-ultrasonic cavitation depolymerization for lignin valorization.

Tandem strategy for lignin utilization with photocatalytic preoxidation and ultrasonic cavitation depolymerization was proposed. Cornstalk residual lignin from industrial bioethanol process was first photocatalytically preoxidized under visible light by g-C3N4 and WO3/g-C3N4/h-BN (WCB) photocatalysts respectively, then obtained lignin samples were characterized to confirm the preoxidation with raw lignin as a blank. During photocatalytic preoxidation, benzyl hydroxyls in lignin was transformed to carbonyls, but a certain degree of lignin degradation and condensation was observed. In comparison, WCB-catalyzed photopreoxidation was more effective. Thereafter, lignin depolymerization was achieved by ultrasonic cavitation-assisted ethanololysis under optimal conditions. Compared with the mere ultrasonic cavitation depolymerization of pristine lignin, WCB-induced photocatalytic preoxidation improved the conversion rate by 14%, the light-oil yield by 26%, and the phenolic monomer yield by 35%. In general, the reported tandem method worked very well for the enhancement of lignin depolymerization and provided a new idea for the development of lignin valorization.

Imaging Intracellular Drug/siRNA Co-Delivery by Self-Assembly Cross-Linked Polyethylenimine with Fluorescent Core-Shell Silica Nanoparticles.

Multifunctional theranostic nanomaterial represents one type of emerging agent with the potential to offer both sensitive diagnosis and effective therapy. Herein, we report a novel drug/siRNA co-delivery nanocarrier, which is based on fluorescent mesoporous core-shell silica nanoparticles coated by cross-linked polyethylenimine. The fluorescent mesoporous core-shell silica nanoparticles can provide numerous pores for drug loading and negative charged surface to assemble cross-linked polyethylenimine via electrostatic interaction. Disulfide cross-linked polyethylenimine can be absorbed on the surface of silica nanoparticles which provide the feasibility to bind with negatively charged siRNA and release drug "on-demand". In addition, the hybrid nanoparticles can be easily internalized into cells to realize drug/siRNA co-delivery and therapeutic effect imaging. This work would stimulate interest in the use of self-assembled cross-linked polyethylenimine with fluorescent mesoporous core-shell silica nanoparticles to construct multifunctional nanocomposites for tumor therapy.

Quantitative Chemoproteomic Profiling of Targets of Au(I) Complexes by Competitive Activity-Based Protein Profiling.

Owing to the encouraging pharmacological action and acceptable toxicity profile, Au(I) complexes have attracted growing interest in the application of disease treatment. In order to investigate their potential target proteins and related bioinformation, herein, we screened four Au(I) complexes and explored the binding proteins utilizing a competitive activity-based protein profiling (ABPP) strategy, including identification experiments and reactivity classification experiments, which offers a simple and robust method to identify the target proteins of Au(I) complexes. We quantified the target proteins of the four Au(I) complexes and found that most of proteins were associated with cancer. In addition, the newly Au(I)-binding proteins and biological gold-protein interaction pathways were exhibited. Furthermore, we estimated the correlation between target proteins of Au(I) complexes and various cancers, which will promote the development of the gold anticancer drugs.

The complete chloroplast genome sequence of Ehretia dicksonii Hance (Ehretiaceae).

Ehretia dicksonii_Hance 1862 is a deciduous botany of Ehretiaceae. In this work, the complete chloroplast (cp) genome sequence of E. dicksonii was probed by next generation sequencing in an effort to provide genomic resources useful for promoting its conservation. The complete cp genome of E. dicksonii is 156,623 bp in length, including a large single-copy (LSC) region of 86,853 bp, and a small single-copy (SSC) region of 18,150 bp. It contains 133 genes, including 37 tRNA genes, 8 rRNA genes, and 88 protein-coding genes. The overall GC content of E. dicksonii chloroplast genome is 37.85%. The phylogenetic analysis suggests that E. dicksonii is in the clade of Ehretiaceae other than Boraginaceae. Also, E. dicksonii has a close relationship with Ehretia acuminata_Brown 1810 in Ehretiaceae.

Palladium(II)-Catalyzed C(sp2)-H Bond Activation/C-N Bond Cleavage Annulation of N-Methoxy Amides and Arynes.

The Pd(II)-catalyzed C-H bond activation/C-N bond cleavage annulation reaction of N-alkyoxyamide aryne is developed to synthesize 9,10-dihydrophenanthrenone derivatives. This reaction exhibited good functional group compatibility with yields up to 92%. Detailed mechanistic studies showed that the key to C-N bond cleavage is the formed eight-membered palladacycle intermediate undergoing nucleophilic addition to the carbonyl group, which provides a new and practical way for N-alkoxyamide directed C-H bond activation.