A metal-organic framework signaling probe-mediated immunosensor for the economical and rapid determination of enrofloxacin in milk.

Ensuring the safety of animal-derived foods requires the reliable and swift identification of enrofloxacin residues to monitor the presence of antibiotics. In this regard, we synthesized, tuned, and investigated the optical properties of a bimetallic metal-organic framework (Ce/Zr-UiO 66). The investigation was facilitated by employing a polydopamine-coated pipette tip with high adsorption efficiency, serving as an immunoreactive carrier. Subsequently, an immunofunctionalized variant of Ce/Zr-UiO 66, referred to as Ce/Zr-UiO 66@ Bovine serum albumin-enrofloxacin, was developed as an optical probe for the rapid and sensitive identification of enrofloxacin across a variety of samples. The method can accurately detect enrofloxacin at concentrations as low as 0.12 ng/mL, with a determination time of under 15 min; furthermore, it demonstrates exceptional efficacy when applied to food, environmental, and clinical samples. The implementation of this methodology offers a valuable means for cost-effective, rapid, and on-site enrofloxacin determination.

Assessment of Wound-Related Pain Experiences of Patients With Chronic Wounds: A Multicenter Cross-Sectional Study in Eastern China.

PURPOSE: The primary aims of this study were to evaluate the prevalence of wound-related pain (WRP) in patients with chronic wounds and assess the use of pain relief measures. DESIGN: A cross-sectional study. SUBJECTS AND SETTING: A convenience sample of patients with chronic wounds was recruited from outpatient clinics of 12 hospitals covering 7 of 13 cities in the Jiangsu province located in eastern China from July 10 to August 25, 2020. The sample comprised 451 respondents, and their mean age was 54.85 (SD 19.16) years; 56.1% (253/451) patients were male. METHODS: An investigator-designed questionnaire was used to collect pain-related information from patients. The questionnaire consisted of 4 parts: (1) basic demographic and clinical information (patient and wound characteristics); (2) wound baseline pain; (3) wound-related procedural pain and pain relief method; and (4) the effect of WRP on the patient. Pain was assessed using the Numerical Rating Scale (NRS) scored from 0 (no pain) to 10 (worst pain). Severity of pain was based on NRS scores' classification as mild (1-3), moderate (4-6), and severe (7-10). The survey was conducted from July 10 to August 25, 2020. Participants were instructed on use of the NRS and then completed the questionnaire following dressing change independently. RESULTS: The 3 most common types of chronic wounds were traumatic ulcers, surgical wounds, and venous leg ulcers. The 3 most prevalent locations were lower limbs, feet, and thorax/abdomen. Of all patients, 62.5% (282/451) and 93.8% (423/451) patients experienced wound baseline pain and wound-related procedural pain, respectively. The mean score of wound baseline pain was 3.76 (SD 1.60) indicating moderate pain. During wound management, the highest pain score was 6.45 (SD 2.75) indicating severe pain; the most severe pain scores were associated with debridement. The use of drugs to relieve wound pain was low, while the use of nondrug-based analgesia was relatively high. Because of WRP, patients with chronic wounds feared dressing changes, hesitated to move, and showed a decline in sleep quality. CONCLUSIONS: Wound baseline pain and wound-related procedural pain were very common in patients with chronic wounds. In the future, targeted intervention plans should be developed by combining drug-based and nondrug-based analgesia according to pain severity.

Unraveling the mechanism in l-Caldesmon regulating the osteogenic differentiation of PDLSCs: An innovative perspective.

Maxillofacial bone defect is one of the common symptoms in maxillofacial, which affects the function and aesthetics of maxillofacial region. Periodontal ligament stem cells (PDLSCs) are extensively used in bone tissue engineering. The mechanism that regulates the osteogenic differentiation of PDLSCs remains not fully elucidated. Previous studies demonstrated that l-Caldesmon (l-CALD, or CALD1) might be involved in the osteogenic differentiation of PDLSCs. Here, the mechanism by which CALD1 regulates the osteogenic differentiation of PDLSCs is investigated. The osteogenic differentiation of PDLSCs is enhanced with Cald1 knockdown. Whole transcriptome sequencing (RNA-seq) analysis shows that bone morphogenetic proteins (BMP) signaling pathway and Wingless type (Wnt) pathway have significant change with Cald1 knockdown, and the expressions of Wnt-induced secreted protein 1 (WISP1), BMP2, Smad1/5/9, and p-Smad1/5/9 are significantly upregulated, while Glycogen synthase kinase 3ß (GSK3ß) and p-GSK3ß are downregulated. In addition, subcutaneous implantation in nude mice shows that knockdown of Cald1 enhances the osteogenic differentiation of PDLSCs in vivo. Taken together, this study demonstrates that knockdown of Cald1 enhances the osteogenic differentiation of PDLSCs by BMP and Wnt signaling pathways, and provides a novel approach for subsequent clinical treatment.

Community-Level Practice Checklists for Health Protection During Cold Spells in China.

Communities play a crucial role in protecting the health of vulnerable populations such as the elderly, low-income groups, and high-risk individuals during cold spells. However, current strategies for responding to cold spells primarily consist of programmatic policies that lack practicality, specificity, and detailed implementation guidelines for community workers. Therefore, this study aims to identify and analyze the challenges faced by communities in responding to cold spells, review international experiences, and develop a set of practical checklists for community-level health protection. These checklists will assist community workers and volunteers in effectively preparing for, responding to, and recovering from cold spells.

USP7 as an emerging therapeutic target: A key regulator of protein homeostasis.

Maintaining protein balance within a cell is essential for proper cellular function, and disruptions in the ubiquitin-proteasome pathway, which is responsible for degrading and recycling unnecessary or damaged proteins, can lead to various diseases. Deubiquitinating enzymes play a vital role in regulating protein homeostasis by removing ubiquitin chains from substrate proteins, thereby controlling important cellular processes, such as apoptosis and DNA repair. Among these enzymes, ubiquitin-specific protease 7 (USP7) is of particular interest. USP7 is a cysteine protease consisting of a TRAF region, catalytic region, and C-terminal ubiquitin-like (UBL) region, and it interacts with tumor suppressors, transcription factors, and other key proteins involved in cell cycle regulation and epigenetic control. Moreover, USP7 has been implicated in the pathogenesis and progression of various diseases, including cancer, inflammation, neurodegenerative conditions, and viral infections. Overall, characterizing the functions of USP7 is crucial for understanding the pathophysiology of diverse diseases and devising innovative therapeutic strategies. This article reviews the structure and function of USP7 and its complexes, its association with diseases, and its known inhibitors and thus represents a valuable resource for advancing USP7 inhibitor development and promoting potential future treatment options for a wide range of diseases.

Molecular insights into the proteomic composition of porcine treated dentin matrix.

Background: Human-treated dentin matrix (hTDM) has recently been studied as a natural extracellular matrix-based biomaterial for dentin pulp regeneration. However, porcine-treated dentin matrix (pTDM) is a potential alternative scaffold due to limited availability. However, there is a dearth of information regarding the protein composition and underlying molecular mechanisms of pTDM.Methods: hTDM and pTDM were fabricated using human and porcine teeth, respectively, and their morphological characteristics were examined using scanning electron microscopy. Stem cells derived from human exfoliated deciduous teeth (SHEDs) were isolated and characterized using flow cytometry and multilineage differentiation assays. SHEDs were cultured in three-dimensional environments with hTDM, pTDM, or biphasic hydroxyapatite/tricalcium phosphate. The expression of odontogenesis markers in SHEDs were assessed using real-time polymerase chain reaction and immunochemical staining. Subsequently, SHEDs/TDM and SHEDs/HA/TCP complexes were transplanted subcutaneously into nude mice. The protein composition of pTDM was analyzed using proteomics and compared to previously published data on hTDM.Results: pTDM and hTDM elicited comparable upregulation of odontogenesis-related genes and proteins in SHEDs. Furthermore, both demonstrated the capacity to stimulate root-related tissue regeneration in vivo. Proteomic analysis revealed the presence of 278 protein groups in pTDM, with collagens being the most abundant. Additionally, pTDM and hTDM shared 58 identical proteins, which may contribute to their similar abilities to induce odontogenesis. Conclusions: Both hTDM and pTDM exhibit comparable capabilities in inducing odontogenesis, potentially owing to their distinctive bioactive molecular networks.

Effects of high-pressure microfluidization treatment on the structural, physiochemical properties of insoluble dietary fiber in highland barley bran.

High-pressure microfluidization treatment (HPMT) was performed on the insoluble dietary fiber (IDF) of highland barley bran (HBB), with conditions set at 60 MPa (IDF-60), 120 MPa (IDF-120), and two consecutive high-pressure treatments at 120 MPa (IDF-120-2), respectively. Then the particle size, structural, physicochemical and adsorption properties of different IDF samples were analyzed. After HPMT, the particle size of IDF samples gradiently decreased (p < 0.05), and part of IDF was transferred into soluble dietary fiber (SDF), accompanied by the decrease of hemicellulose and lignin content. In addition, the morphology of the IDF samples became more fragmented and wrinkled, and the two consecutive treatments at 120 MPa significantly damaged the crystalline structure of the IDF. Moreover, the adsorption capacities to water, oil, cholesterol, and NO2- were basically enhanced with the increase of treatment pressure and treatment number. The IDF-120-2 sample had the strongest water/oil-holding, swelling, and cholesterol trapping capacities, and the IDF-120 showed strongest NO2- trapping capacity (pH = 2). Through the correlation analysis, the adsorption capacities were positively to the particle size and SDF content, and negatively correlated with the specific surface area (SSA) and IDF content. The adsorption capacities of IDF for the four substances were positively correlated with each other.

Thick endometrium is associated with hypertensive disorders of pregnancy in programmed frozen-thawed embryo transfers: a retrospective analysis of 2,275 singleton deliveries.

OBJECTIVE: To investigate whether endometrial thickness (EMT) acts as a contributing factor to adverse perinatal outcomes in programmed frozen-thawed embryo transfer (FET) cycles. DESIGN: Retrospective cohort study. SETTING: University-based reproductive medical center. SUBJECT: The study included singleton live births resulting from programmed FET cycles that took place between January 2017 and April 2022 (N = 2,275 cycles). EXPOSURE: The EMT measurement conducted on the day of progesterone initiation was utilized. Programmed FET cycles with EMT <7 mm were excluded from consideration. All included subjects were divided into 4 groups on the basis of the 10th, 50th, and 90th percentiles of EMT: group Ⅰ (EMT ≤8 mm, n = 193), group Ⅱ (EMT = 8.1-10 mm, n = 1,261), group Ⅲ (EMT = 10.1-12 mm, n = 615), and group Ⅳ (EMT >12 mm, n = 206). After adjusting for patient demographics and FET parameters, logistic regression analysis and restricted cubic spline were used to investigate the relationship between EMT and perinatal outcomes. The group Ⅱ (EMT = 8.1-10 mm) served as a reference. MAIN OUTCOME MEASURE(S): The primary outcome measure was the hypertensive disorders of pregnancy (HDP). Secondary outcomes included gestational diabetes mellitus, cesarean delivery, placenta previa, premature rupture of membrane, birthweight, preterm birth, low birthweight, macrosomia, small for gestational age, large for gestational age and neonatal morbidity. RESULTS(S): The incidence of HDP was substantially elevated in group Ⅳ when compared with the other groups (5.7% vs. 4.1% vs. 5.7% vs. 9.7% for groups Ⅰ-Ⅳ, respectively). In addition, group I displayed a higher incidence of cesarean deliveries, whereas both group I and group IV exhibited an elevated prevalence of placenta previa. After adjusting for confounding factors, patients in group IV exhibited a significantly increased risk of HDP (adjusted odds ratio [OR] = 2.03, 95% confidence interval [CI] 1.13-3.67) as compared with patients in the reference group. The restricted cubic spline model revealed a nonlinear association between EMT and the odds of HDP on continuous scales. In comparison to women with an EMT of 9.5 mm, there was no significant change in the risk of HDP in women with EMT between 7 and 11 mm, as indicated by adjusted ORs of 1.37 (95% CI 0.41-4.52), 1.34 (95% CI 0.73-2.47), 1.13 (95% CI 0.79-1.62), 1.04 (95% CI 0.87-1.25), and 1.46 (95% CI 0.81-2.65), respectively. However, the risk of HDP was significantly higher in women with EMT ranging from 12 to 15 mm, with adjusted ORs of 1.86 (95% CI 1.03-3.35), 2.33 (95% CI 1.32-4.12), 2.92 (95% CI 1.52-5.60), and 3.62 (95% CI 1.63-8.04), respectively. CONCLUSION(S): This study demonstrated a noteworthy association between EMT and adverse perinatal outcomes during the programmed FET cycles. Specifically, a thick endometrium (EMT >12 mm) was independently associated with an increased risk of developing HDP, whereas the optimal EMT for reducing the risk of HDP was at around 9-10 mm.

Current therapies for osteoarthritis and prospects of CRISPR-based genome, epigenome, and RNA editing in osteoarthritis treatment.

Osteoarthritis (OA) is one of the most common degenerative joint diseases worldwide, causing pain, disability, and decreased quality of life. The balance between regeneration and inflammation-induced degradation results in multiple etiologies and complex pathogenesis of OA. Currently, there is a lack of effective therapeutic strategies for OA treatment. With the development of CRISPR-based genome, epigenome, and RNA editing tools, OA treatment has been improved by targeting genetic risk factors, activating chondrogenic elements, and modulating inflammatory regulators. Supported by cell therapy and in vivo delivery vectors, genome, epigenome, and RNA editing tools may provide a promising approach for personalized OA therapy. This review summarizes CRISPR-based genome, epigenome, and RNA editing tools that can be applied to the treatment of OA and provides insights into the development of CRISPR-based therapeutics for OA treatment. Moreover, in-depth evaluations of the efficacy and safety of these tools in human OA treatment are needed.

Time-resolved fluorescence microspheres-antibody-penicillin-binding protein assisted construction of immunochromatographic assay for sensitive detection of 22 ß-lactams in milk.

A sensitive immunochromatographic assay (ICA) using time-resolved fluorescence microspheres (TRFMs) coupled with an indirect-labeling mode was developed for simultaneously determining 22 kinds of ß-lactams in milk samples. The TRFMs labeled anti-receptor monoclonal antibodies (mAbs) conjugated to penicillin-binding proteins (PBPs) as ternary TRFMs-mAb-PBPs (TMP) nanoscaffolds provide excellent solubility, brightness, and stability. Thanks to the fact that they not only fully expose the binding sites of PBPs, thereby enhancing the biological affinity of PBPs towards the target, but also generated superb fluorescence signals, the versatile TMP manifested unique possibilities as efficient probes for ICA with remarkable enhancement in sensitivity in ß-lactams screening. The results showed that the standard curves of the 22 varying ß-lactams displayed linearity in their respective concentration ranges (R2 > 0.98), with the cutoff values of 1-100 ng/mL. The constructed TMP-ICA was successfully applied to the analysis of real milk, with consistent results compared with liquid chromatography-tandem mass spectrometry (LC-MS), providing an effective method for sensing ß-lactams in food matrices.

Production of monoclonal antibody against tylosin and tilmicosin with homogeneous cross-reactivity and its application in lateral flow immunoassay.

To avoid false negative results due to the low cross-reactivity rate (CR) in rapid immunoassay, a group-specific antibody with homogeneous CR toward target compounds is needed for accuracy. In this study, tylosin (TYL) and tilmicosin (TM) were selected as model molecules. Firstly, two-dimensional similarity, electrostatic potential energy, spatial conformation and charge distribution of the haptens TYL-CMO, TYL-6-ACA, TYL-4-APA, TYL-CHO and DES-CMO and target compounds of TYL and TM were obtained using Gaussian 09W and Discovery Studio. The optimal hapten was DES-CMO because it is the most similar to TYL and TM. Subsequently, the mAb 14D5 cell line was obtained with IC50 values of 1.59 and 1.72 ng/mL for TYL and TM, respectively, and a CR of 92.44%. Finally, amorphous carbon nanoparticles (ACNPs) were conjugated with mAb 14D5 to develop an accurate lateral flow immunoassay (LFA) for detection of TYL and TM by the reflectance value under natural light. The recoveries of TYL and TM ranged from 77.18 to 112.04% with coefficient of variation < 13.43%. The cut-off value in milk samples was 8 ng/mL, and the limits of detection were 11.44, 15.96, 22.29 and 25.53 µg/kg for chicken muscle, bovine muscle, porcine muscle and porcine liver samples, respectively, and the results being consistent with HPLC-UV. The results suggest that the developed LFA is accurate and potentially useful for on-site screening of TYL and TM in milk and animal tissue samples.

Development of a monoclonal antibody-based lateral flow immunoassay for the detection of benzoic acid in liquid food.

To monitor benzoic acid (BA) residues in liquid food samples, a monoclonal antibody (mAb)-based lateral flow immunoassay (LFA) was developed in this study. First, 2-aminobenzoic acid (2-AA), 3-aminobenzoic acid (3-AA), and 4-aminobenzoic acid (4-AA) were conjugated to BSA and used as immunogens. After cell fusion, mAb 6D8 from 4-AA-BSA performed best with an IC50 value of 0.21 mg L-1 using 3-AA-OVA as a heterogeneous antigen, which represented a 3.4-fold improvement compared with the homogeneous antigen 4-AA-BSA. Subsequently, eight kinds of CGNPs with sizes varying from 20.94 nm to 90.00 nm were synthesized for screening the suitable size to develop a sensitive LFA. Finally, a sensitive LFA based on colloidal gold (23.27 nm) nanoparticles was developed for screening BA with a cut-off value of 4 mg L-1, which could meet the requirement of BA detection in milk, Fanta, Sprite, Coca-Cola, and Smart samples.

The Communication from Immune Cells to the Fibroblasts in Keloids: Implications for Immunotherapy.

Keloids are a type of fibrotic disease characterized by excessive collagen production and extracellular matrix (ECM) deposition. The symptoms of pain and itching and frequent recurrence after treatment significantly impact the quality of life and mental health of patients. A deeper understanding of the pathogenesis of keloids is crucial for the development of an effective therapeutic approach. Fibroblasts play a central role in the pathogenesis of keloids by producing large amounts of collagen fibers. Recent evidence indicates that keloids exhibit high immune cell infiltration, and these cells secrete cytokines or growth factors to support keloid fibroblast proliferation. This article provides an update on the knowledge regarding the keloid microenvironment based on recent single-cell sequencing literature. Many inflammatory cells gathered in keloid lesions, such as macrophages, mast cells, and T lymphocytes, indicate that keloids may be an inflammatory skin disease. In this review, we focus on the communication from immune cells to the fibroblasts and the potential of immunotherapy for keloids. We hope that this review will trigger interest in investigating keloids as an inflammatory disease, which may open up new avenues for drug development by targeting immune mediators.

Effect of noninvasive embryo viability testing versus conventional IVF on the live birth rate in IVF/ICSI patients: a study protocol for a double-blind, multicenter, randomized controlled trial.

BACKGROUND: Preimplantation genetic testing for aneuploidy (PGT-A) was demonstrated to be superior to conventional IVF in reducing the incidence of miscarriage and abnormal offspring after the first embryo transfer (ET). PGT-A requires several embryo trophectoderm cells, but its negative impacts on embryo development and long-term influence on the health conditions of conceived children have always been a concern. As an alternative, noninvasive PGT-A (niPGT-A) approaches using spent blastocyst culture medium (SBCM) achieved comparable accuracy with PGT-A in several pilot studies. The main objective of this study is to determine whether noninvasive embryo viability testing (niEVT) results in better clinical outcomes than conventional IVF after the first embryo transfer. Furthermore, we further investigated whether niEVT results in higher the live birth rate between women with advanced maternal age (AMA, > 35 years old) and young women or among patients for whom different fertilization protocols are adopted. METHODS: This study will be a double-blind, multicenter, randomized controlled trial (RCT) studying patients of different ages (20-43 years) undergoing different fertilization protocols (in vitro fertilization [IVF] or intracytoplasmic sperm injection [ICSI]). We will enroll 1140 patients at eight reproductive medical centers over 24 months. Eligible patients should have at least two good-quality blastocysts (better than grade 4 CB). The primary outcome will be the live birth rate of the first embryo transfer (ET). Secondary outcomes will include the clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, cumulative live birth rate, ectopic pregnancy rate, and time to pregnancy. DISCUSSION: In this study, patients who undergo noninvasive embryo viability testing (niEVT) will be compared to women treated by conventional IVF. We will determine the effects on the pregnancy rate, miscarriage rate, and live birth rate and adverse events. We will also investigate whether there is any difference in clinical outcomes among patients with different ages and fertilization protocols (IVF/ICSI). This trial will provide clinical evidence of the effect of noninvasive embryo viability testing on the clinical outcomes of the first embryo transfer. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) Identifier: ChiCTR2100051408. 9 September 2021.

A Comparable icELISA and Lateral Flow Immunoassay for the Sensitive and Rapid Detection of 4,4'-Dinitrocarbanilide in Chicken.

4,4'-dinitrocarbanilide (DNC) is a key component and marker residue of nicarbazin, which forms residues in edible tissue and then causes nephrotoxicity and hepatotoxicity in humans if used excessively. To simplify sample preparation and monitor the DNC rapidly and accurately, a comparable icELISA and lateral flow immunoassay (LFIA) was developed in this study. Briefly, the reaction parameters were explored for improving the sensitivity of icELISA and LFIA. Under the optimal conditions, methanol was selected as the extracting solvent for DNC in chicken, and 20- and 10-fold dilutions of sample extraction eliminated the matrix effect for icELISA and LFIA, separately. After sample pretreatment, the analysis properties of icELISA and LFIA were compared. The limit of detection of icELISA for DNC was 0.8 µg/kg, and the visual and quantitative limits of detection of LFIA were 8 and 2.5 µg/kg. Compared with icELISA, LFIA showed lower sensitivity but obvious advantages in terms of matrix tolerance and detection time (within 15 min). The sensitivity, specificity, and accuracy of the developed assays satisfied the detection requirement even if using simple sample pretreatment. This comparable icELISA and LFIA provided mutual verifiability methods for the accurate detection of DNC in chicken.

Loss of gdnfa disrupts spermiogenesis and male courtship behavior in zebrafish.

Spermatogenesis is essential for establishment and maintenance of reproduction in male vertebrates. Spermatogenesis, which is mainly regulated by the combined action of hormones, growth factors, and epigenetic factors, is highly conserved. Glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor-ß superfamily. In this study, global gdnfa knockout and Tg (gdnfa: mcherry) transgenic zebrafish lines were generated. Loss of gdnfa resulted in disorganized testes, decreased gonadosomatic index, and low percentage of mature spermatozoa. In the Tg (gdnfa: mcherry) zebrafish line, we found that gdnfa was expressed in Leydig cells. The mutation in gdnfa significantly decreased Leydig cell marker gene expression and androgen secretion in Leydig cells. In addition, courtship behavior was disrupted in the male mutants. We present in vivo data showing that global knockout of gdnfa disrupts spermiogenesis and male courtship behavior in zebrafish. The first viable vertebrate model with a global gdnfa knockout may be valuable for studying the role of GDNF in animal reproduction.

Development of a Lateral Flow Immunoassay Based on a Highly Specific Monoclonal Antibody To Detect 4-Methylaminoantipyrine.

To avoid false-positive results in immunoassays due to cross-reactivity of antibodies with structural analogues, especially metabolites of target compounds, the preparation of highly specific antibodies is crucial. Preserving the characteristic structure of a target compound when designing a hapten is important when preparing highly specific antibodies. Here, we designed a novel hapten, 4-(((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4yl)amino)methyl)benzoic acid, named AA-BA, to improve the specificity of antibodies for detection of 4-methylaminoantipyrine (MAA), a residual marker of dipyrone, an important antipyretic-analgesic and anti-inflammatory drug. The structural features of the hapten remained almost the same as those of MAA. After experimental validation, monoclonal antibody 6A4 (mAb 6A4) was prepared with the half maximal inhibitory concentration (IC50) value of 4.03 ng/mL and negligible cross-reactivity with dipyrone metabolites and other antibiotics. In addition, a specific lateral flow immunoassay (LFA) strip based on colloidal gold was developed for screening MAA with a cutoff value of 25 ng/mL in milk. The developed LFA is a useful tool for rapid and accurate detection of MAA.

New insights into the non-enzymatic function of HDAC6.

Histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase that contains two catalytic domains and a zinc-finger ubiquitin binding domain (ZnF-UBP) domain. The deacetylation function of HDAC6 has been extensively studied with common substrates such as α-tubulin, cortactin, and Hsp90. Apart from its deacetylase activity, HDAC6 ZnF-UBP binds to unanchored ubiquitin of specific sequences and serves as a carrier for transporting aggregated proteins. As a result, aggresomes are formed and protein degradation is facilitated by the autophagy-lysosome pathway. This HDAC6-dependent microtubule transport can be used by cells to assemble and activate inflammasomes, which play a critical role in immune regulation. Even viruses can benefit from the carrier of HDAC6 to assist in uncoating their surfaces during their infection cycle. However, HDAC6 is also capable of blocking virus invasion and replication in a non-enzymatic manner. Given these non-enzymatic functions, HDAC6 is closely associated with various diseases, including neurodegeneration, inflammasome-associated diseases, cancer, and viral infections. Small molecule inhibitors targeting the ubiquitin binding pocket of HDAC6 have been investigated. In this review, we focus on mechanisms in non-enzymatic functions of HDAC6 and discuss the rationality and prospects of therapeutic strategies by intervening the activation of HDAC6 ZnF-UBP in concrete diseases.

A highly sensitive lateral flow immunoassay based on a group-specific monoclonal antibody and amorphous carbon nanoparticles for detection of sulfonamides in milk.

To meet high-throughput screening of the residues of sulfonamides (SAs) with high sensitivity toward sulfamethazine (SM2) in milk samples, a new highly sensitive lateral flow immunoassay (LFA) based on amorphous carbon nanoparticles (ACNs) was developed. First, a group-specific monoclonal antibody 10H7 (mAb 10H7) that could recognize 25 SAs with high sensitivity toward SM2 (IC50 value of 0.18 ng/mL) was prepared based on H1 as an immune hapten and H4 as a heterologous coating hapten. Then, mAb 10H7 was conjugated to ACNs as an immune probe for LFA development. Under the optimized conditions, the LFA could detect 25 SAs with the cut-off value toward SM2 of 2 ng/mL, which could meet the requirement for detection of SAs. In addition, the LFA developed was also used for screening SAs' residues in real milk samples, with results being consistent with HPLC-MS/MS. Thus, this LFA can be used as a high-throughput screening tool for detection of SAs.

Detailed curriculum vitae of HER2-targeted therapy.

With the booming development of precision medicine, molecular targeted therapy has been widely used in clinical oncology treatment due to a smaller number of side effects and its superior accuracy compared to that of traditional strategies. Among them, human epidermal growth factor receptor 2 (HER2)-targeted therapy has attracted considerable attention and has been used in the clinical treatment of breast and gastric cancer. Despite excellent clinical effects, HER2-targeted therapy remains in its infancy due to its resulting inherent and acquired resistance. Here, a comprehensive overview of HER2 in numerous cancers is presented, including its biological role, involved signaling pathways, and the status of HER2-targeted therapy.