Distinct multitrophic biodiversity composition and community organization in a freshwater lake and a hypersaline lake on the Tibetan Plateau.

Alpine lakes play pivotal roles in plateau hydrological processes but are highly sensitive to climate change, yet we lack comprehensive knowledge of their multitrophic biodiversity patterns. Here, we compared the biodiversity characteristics of diverse taxonomic groups across water depths and in surface sediments from a freshwater lake and a hypersaline lake on the northwestern Tibetan Plateau. Using multi-marker environmental DNA metabarcoding, we detected 134 cyanobacteria, 443 diatom, 1,519 invertebrate, and 28 vertebrate taxa. Each group had a substantially different community composition in the two lakes, and differences were also found between water and sediments within each lake. Cooccurrence network analysis revealed higher network complexity, lower modularity, and fewer negative cohesions in the hypersaline lake, suggesting that high salinity may destabilize ecological networks. Our results provide the first holistic view of Tibetan lake biodiversity under contrasting salinity levels and reveal structural differences in the ecological networks that may impact ecosystem resilience.

Research progress of ubiquitin and ubiquitin-like signaling in Toxoplasma gondii.

Toxoplasmosis, a zoonotic parasitic disease caused by Toxoplasma gondii (T. gondii), is prevalent worldwide. The fact should be emphasized that a considerable proportion of individuals infected with T. gondii may remain asymptomatic; nevertheless, the condition can have severe implications for pregnant women or immunocompromised individuals. The current treatment of toxoplasmosis primarily relies on medication; however, traditional anti-toxoplasmosis drugs exhibit significant limitations in terms of efficacy, side effects, and drug resistance. The life cycles of T. gondii are characterized by distinct stages and its body morphology goes through dynamic alterations during the growth cycle that are intricately governed by a wide array of post-translational modifications (PTMs). Ubiquitin (Ub) signaling and ubiquitin-like (Ubl) signaling are two crucial post-translational modification pathways within cells, regulating protein function, localization, stability, or interactions by attaching Ub or ubiquitin-like proteins (Ubls) to target proteins. While these signaling mechanisms share some functional similarities, they have distinct regulatory mechanisms and effects. T. gondii possesses both Ub and Ubls and plays a significant role in regulating the parasite's life cycle and maintaining its morphology through PTMs of substrate proteins. Investigating the role and mechanism of protein ubiquitination in T. gondii will provide valuable insights for preventing and treating toxoplasmosis. This review explores the distinctive characteristics of Ub and Ubl signaling in T. gondii, with the aim of inspiring research ideas for the identification of safer and more effective drug targets against toxoplasmosis.

From macroautophagy to mitophagy: Unveiling the hidden role of mitophagy in gastrointestinal disorders.

In this editorial, we comment on an article titled "Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases", which was published in a recent issue of the World Journal of Gastroenterology. We focused on the statement that "autophagy is closely related to the digestion, secretion, and regeneration of gastrointestinal cells". With advancing research, autophagy, and particularly the pivotal role of the macroautophagy in maintaining cellular equilibrium and stress response in the gastrointestinal system, has garnered extensive study. However, the significance of mitophagy, a unique selective autophagy pathway with ubiquitin-dependent and independent variants, should not be overlooked. In recent decades, mitophagy has been shown to be closely related to the occurrence and development of gastrointestinal diseases, especially inflammatory bowel disease, gastric cancer, and colorectal cancer. The interplay between mitophagy and mitochondrial quality control is crucial for elucidating disease mechanisms, as well as for the development of novel treatment strategies. Exploring the pathogenesis behind gastrointestinal diseases and providing individualized and efficient treatment for patients are subjects we have been exploring. This article reviews the potential mechanism of mitophagy in gastrointestinal diseases with the hope of providing new ideas for diagnosis and treatment.

Overexpression of COX7A1 Promotes the Resistance of Gastric Cancer to Oxaliplatin and Weakens the Efficacy of Immunotherapy.

Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. Presently, the overall response rate to immunotherapy is low, and current methods for predicting the prognosis of GC are not optimal. Therefore, novel biomarkers with accuracy, efficiency, stability, performance ratio, and wide clinical application are needed. Based on public data sets, the chemotherapy cohort and immunotherapy cohort from Sun Yat-sen University Cancer Center, a series of bioinformatics analyses, such as differential expression analysis, survival analysis, drug sensitivity prediction, enrichment analysis, tumor immune dysfunction and exclusion analysis, single-sample gene set enrichment analysis, stemness index calculation, and immune cell infiltration analysis, were performed for screening and preliminary exploration. Immunohistochemical staining and in vitro experiments were performed for further verification. Overexpression of COX7A1 promoted the resistance of GC cells to Oxaliplatin. COX7A1 may induce immune escape by regulating the number of fibroblasts and their cellular communication with immune cells. In summary, measuring the expression levels of COX7A1 in the clinic may be useful in predicting the prognosis of GC patients, the degree of chemotherapy resistance, and the efficacy of immunotherapy.

BNT12, a novel hybrid peptide of opioid and neurotensin pharmacophores, produces potent central antinociception with limited side effects.

The development of multitarget opioid drugs has emerged as an attractive approach for innovative pain management with reduced side effects. In the present study, a novel hybrid peptide BNT12 containing the opioid and neurotensin (NT)-like fragments was synthesized and pharmacologically characterized. In acute radiant heat paw withdrawal test, intracerebroventricular (i.c.v.) administration of BNT12 produced potent antinociception in mice. The central antinociceptive activity of BNT12 was mainly mediated by µ-, δ-opioid receptor, neurotensin receptor type 1 (NTSR1) and 2 (NTSR2), supporting a multifunctional agonism of BNT12 in the functional assays. BNT12 also exhibited significant antinociceptive effects in spared nerve injury (SNI)-neuropathic pain, complete Freund's adjuvant (CFA)-induced inflammatory pain, acetic acid-induced visceral and formalin-induced pain after i.c.v. administration. Furthermore, BNT12 exhibited substantial reduction of acute antinociceptive tolerance, shifted the dose-response curve to the right by only 1.3-fold. It is noteworthy that BNT12 showed insignificant chronic antinociceptive tolerance at the supraspinal level. In addition, BNT12 exhibited reduced or no opioid-like side effects on conditioned place preference (CPP) response, naloxone-precipitated withdrawal response, acute hyperlocomotion, motor coordination, gastrointestinal transit, and cardiovascular responses. The present investigation demonstrated that the novel hybrid peptide BNT12 might serve as a promising analgesic candidate with limited opioid-like side effects.

Vinorelbine administration impedes the timely progression of meiotic maturation and induces aneuploidy in mouse oocytes.

Vinorelbine is a commonly used drug to treat various malignancies, such as breast cancer, non-small cell lung cancer, and metastatic pleural mesothelioma. Its side effects include severe neutropenia, local phlebitis, gastrointestinal reactions, and neurotoxicity. In view of the scarcity of research on vinorelbine's reproductive toxicity, this study evaluated the impact of vinorelbine ditartrate, a commonly used form of vinorelbine, on oocyte maturation in vitro. Our investigation revealed that vinorelbine ditartrate had no effect on oocyte meiotic resumption. However, it did reduce the rate of first polar body extrusion, suggesting that it could significantly impede the meiotic maturation of oocytes. Vinorelbine ditartrate exposure was found to disturb the regular spindle assembly and chromosome alignment, leading to the continuous activation of the spindle assembly checkpoint (SAC) and a delayed activation of the anaphase-promoting complex/cyclosome (APC/C), ultimately causing aneuploidy in oocytes. Consequently, the administration of vinorelbine is likely to result in oocyte aneuploidy, which can be helpful in providing a drug reference and fertility guidance in a clinical context.

Cinnamaldehyde Regulates the Migration and Apoptosis of Gastric Cancer Cells by Inhibiting the Jak2/Stat3 Pathway.

OBJECTIVE: Gastric cancer is a malignant tumor with high morbidity and mortality all around the world. Because of its poor prognosis and low survival rate, the treatment of gastric cancer has received extensive attention. Cinnamaldehyde (CA) is the main single active component of the Chinese herbal medicine cinnamon, which has a variety of pharmacological effects. The inhibitory effect of CA on the growth of some tumor cells has been proven, but its therapeutic effect on gastric cancer has rarely been reported. METHODS: Through network pharmacology, bioinformatics methods, and molecular docking technology, we predicted the interaction targets of CA and gastric cancer. Moreover, we found that apoptosis is an important mode of action of CA on gastric cancer cells. Subsequently, we validated it in gastric cancer cell lines cultured in vitro. RESULTS: The results showed that in the presence of CA, the Jak2/Stat3 pathway was inhibited, the ratio of Bcl-2/Bax decreased, and the apoptosis of gastric cancer cells was promoted in a concentration-dependent. CONCLUSION: In conclusion, CA can promote the apoptosis of gastric cancer cells by inhibiting the activity of the Jak2/Stat3 pathway, which may achieve the effect of treating gastric cancer.

Multicenter propensity score-matched analysis to compare perioperative morbidity after laparoscopic or robotic complex hepatectomy for solitary hepatocellular carcinoma.

BACKGROUND: Postoperative complications are vital factors affecting the prognosis of patients with hepatocellular carcinoma (HCC), especially for complex hepatectomy. The present study aimed to compare perioperative complications between laparoscopic and robotic complex hepatectomy (LCH vs. RCH). METHODS: Patients with solitary HCC after complex hepatectomy were collected from a multicenter database. Propensity score-matched (PSM) analysis was adopted to control confounding bias. Multivariable analysis was performed to determine the prognostic factors. RESULTS: 436 patients were included. After PSM, 43 patients were included in both the LCH and RCH groups. The results showed that compared to LCH, RCH had lower rates of blood loss and transfusion, and lower postoperative 30-day and major morbidity, and post-hepatectomy liver failure (PHLF) (all P < 0.05). Additionally, the length of hospital stay was shorter in the RCH group (P = 0.026). Multivariable analysis showed RCH is an independent protective factor for reducing the 30-day morbidity, major morbidity and PHLF. CONCLUSION: RCH has advantages over LCH in the minimally invasive treatment of complex HCC, as it can reduce the incidence of postoperative morbidity. Therefore, RCH should be considered for patients with HCC who require complex hepatectomy.

Pathological Mechanism and Treatment of Calcified Aortic Stenosis.

Calcified aortic stenosis (AS) is one of the most common valvular heart diseases worldwide, characterized by progressive fibrocalcific remodeling and thickening of the leaflets, which ultimately leads to obstruction of blood flow. Its pathobiology is an active and complicated process, involving endothelial cell dysfunction, lipoprotein deposition and oxidation, chronic inflammation, phenotypic transformation of valve interstitial cells, neovascularization, and intravalvular hemorrhage. To date, no targeted drug has been proven to slow down or prevent disease progression. Aortic valve replacement is still the optimal treatment of AS. This article reviews the etiology, diagnosis, and management of calcified aortic stenosis and proposes novel potential therapeutic targets.

Research hotspots and trends in biological agents for psoriasis: Visualization and bibliometric analysis.

Psoriasis is a global health concern, and biological therapies have proven to be highly effective in treating psoriatic patients in many countries. We performed a bibliometric analysis of current research on biological agents for the treatments of psoriasis, investigating research patterns and public interest in this area. We conducted a thorough review of articles on biological agents for psoriasis in the Web of Science Core Collection spanning from 2000 to 2022. Our study involved examining the distribution of these articles based on publication year, affiliations, countries, authors, and journals. To visualize this data effectively, we employed bibliometric tools like CiteSpace and the R package bibliometrix. Our analysis encompassed 8,047 publications. The number of papers published sharply increased from 2009, either reaching its peak in 2022 or not yet reaching it. The United States (n = 2,292), Kristian Reich (n = 166), and British Journal of Dermatology (n = 368) emerged as the top countries, author, and journal, respectively, in terms of publication productivity. The burst references predominantly focused on evaluating the safety and efficacy of biological treatments. The keyword citation network identified 11 clusters, with research themes revolving around "double blind", "efficacy", "therapy", "safety", and "psoriatic arthritis" were the research focuses. Additionally, potential future research areas such as "multicenter," "drug survival," and "severity" were emphasized. This study sheds light on the evolving research landscape and public interest in biological agents for psoriasis. The results suggest rapid expansion in this field, with the United States at the forefront. Enhanced international collaboration is recommended, and forthcoming research endeavors may concentrate on predicting treatment outcomes and adverse effects. Researching new biological agents, broadening the indications for biological agent treatment, and creating personalized treatment plans may pave the way for further research.

Injectable Oxygen-Carrying Microsphere Hydrogel for Dynamic Regulation of Redox Microenvironment of Wounds.

The delayed healing of infected wounds can be attributed to the increased production of reactive oxygen species (ROS) and consequent damages to vascellum and tissue, resulting in a hypoxic wound environment that further exacerbates inflammation. Current clinical treatments including hyperbaric oxygen therapy and antibiotic treatment fail to provide sustained oxygenation and drug-free resistance to infection. To propose a dynamic oxygen regulation strategy, this study develops a composite hydrogel with ROS-scavenging system and oxygen-releasing microspheres in the wound dressing. The hydrogel itself reduces cellular damage by removing ROS derived from immune cells. Simultaneously, the sustained release of oxygen from microspheres improves cell survival and migration in hypoxic environments, promoting angiogenesis and collagen regeneration. The combination of ROS scavenging and oxygenation enables the wound dressing to achieve drug-free anti-infection through activating immune modulation, inhibiting the secretion of pro-inflammatory cytokines interleukin-6, and promoting tissue regeneration in both acute and infected wounds of rat skins. Thus, the composite hydrogel dressing proposed in this work shows great potential for dynamic redox regulation of infected wounds and accelerates wound healing without drugs.

Stephaochratidin A, a Rare Stephacidin-Asperochratide Hybrid with Ferroptosis Inhibitory Activity from the Deep-Sea-Derived Aspergillus ochraceus.

One rare stephacidin-asperochratide hybrid, stephaochratidin A (1), was isolated from the deep-sea-derived Aspergillus ochraceus MCCC 3A00521. The relative structure of 1 was determined by comprehensive analyses of its 1D and 2D NMR data as well as HRESIMS data. And the absolute configuration was unambiguously assigned by ECD calculations and the X-ray single-crystal diffraction analysis. Plausible biosynthetic pathway of 1 was proposed. Stephaochratidin A (1) exhibited significant ferroptosis inhibitory activity with the EC50 value of 15.4 µM by downregulating HMOX-1 expression and lipid peroxidation.

Assessment of the Clinical Utility of the FilmArrayTM Gastrointestinal Panel for Detecting Gastrointestinal Pathogens.

BACKGROUND: Gastrointestinal infections present a significant public health concern as they lead to diverse clinical presentations and healthcare challenges. The rapid and accurate identification of causative pathogens is imperative for effective patient management. This study aimed to assess the clinical utility of the FilmArrayTM Gastrointestinal (GI) Panel for detecting gastrointestinal pathogens. METHODS: Between November 1, 2022, and December 31, 2023, we analysed gastrointestinal specimens collected from a cohort of patients aged 21 to 91 at Asia University Hospital. These specimens were analyzed using the FilmArrayTM GI Panel. RESULTS: The study included 76 patients for whom the FilmArrayTM GI assay was conducted, with 40 (52.6%) showing positive results. Among the positive specimens, 23 (57.5%) had a single pathogen, while the remaining 17 (42.5%) had multiple pathogens. The remaining 36 (47.4%) specimens showed no pathogens. The overall positivity rate of the specimens was 52.6%. The most frequently detected pathogens included Salmonella, Clostridium difficile (toxin A/B), and Enteropathogenic Escherichia coli (EPEC). CONCLUSIONS: This study underscores the clinical value of the FilmArrayTM GI assay as a rapid and reliable tool for diagnosing gastrointestinal infections. Its capacity to detect multiple pathogens simultaneously enhances diagnostic accuracy and gives information to use in clinical decision-making. We strongly recommend its integration into clinical practice to expedite the diagnosis and management of gastrointestinal infections, ultimately leading to improved patient care and healthcare efficiency.

Safety, efficacy, and survival outcomes of immune checkpoint inhibitors rechallenge in patients with cancer: a systematic review and meta-analysis.

BACKGROUNDS: There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due to immune-related adverse events (irAEs) or progressive disease (PD). Here, we performed a meta-analysis to elucidate the possible benefits of ICI rechallenge in patients with cancer. METHODS: Systematic searches were conducted using PubMed, Embase, and Cochrane Library databases. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of irAEs were the outcomes of interest. RESULTS: Thirty-six studies involving 2026 patients were analyzed. ICI rechallenge was associated with a lower incidence of all-grade (OR, 0.05; 95%CI, 0.02-0.13, P < .05) and high-grade irAEs (OR, 0.37; 95%CI, 0.21-0.64, P < .05) when compared with initial ICI treatment. Though no significant difference was observed between rechallenge and initial treatment regarding ORR (OR, 0.69; 95%CI, 0.39-1.20, P = .29) and DCR (OR, 0.85; 95%CI, 0.51-1.40, P = 0.52), patients receiving rechallenge had improved PFS (HR, 0.56; 95%CI, 0.43-0.73, P < .05) and OS (HR, 0.55; 95%CI, 0.43-0.72, P < .05) than those who discontinued ICI therapy permanently. Subgroup analysis revealed that for patients who stopped initial ICI treatment because of irAEs, rechallenge showed similar safety and efficacy with initial treatment, while for patients who discontinued ICI treatment due to PD, rechallenge caused a significant increase in the incidence of high-grade irAEs (OR, 4.97; 95%CI, 1.98-12.5, P < .05) and a decrease in ORR (OR, 0.48; 95%CI, 0.24-0.95, P < .05). CONCLUSION: ICI rechallenge is generally an active and feasible strategy that is associated with relative safety, similar efficacy, and improved survival outcomes. Rechallenge should be considered individually with circumspection, and randomized controlled trials are required to confirm these findings.

Organic fertilization co-selects genetically linked antibiotic and metal(loid) resistance genes in global soil microbiome.

Antibiotic resistance genes (ARGs) and metal(loid) resistance genes (MRGs) coexist in organic fertilized agroecosystems based on their correlations in abundance, yet evidence for the genetic linkage of ARG-MRGs co-selected by organic fertilization remains elusive. Here, an analysis of 511 global agricultural soil metagenomes reveals that organic fertilization correlates with a threefold increase in the number of diverse types of ARG-MRG-carrying contigs (AMCCs) in the microbiome (63 types) compared to non-organic fertilized soils (22 types). Metatranscriptomic data indicates increased expression of AMCCs under higher arsenic stress, with co-regulation of the ARG-MRG pairs. Organic fertilization heightens the coexistence of ARG-MRG in genomic elements through impacting soil properties and ARG and MRG abundances. Accordingly, a comprehensive global map was constructed to delineate the distribution of coexistent ARG-MRGs with virulence factors and mobile genes in metagenome-assembled genomes from agricultural lands. The map unveils a heightened relative abundance and potential pathogenicity risks (range of 4-6) for the spread of coexistent ARG-MRGs in Central North America, Eastern Europe, Western Asia, and Northeast China compared to other regions, which acquire a risk range of 1-3. Our findings highlight that organic fertilization co-selects genetically linked ARGs and MRGs in the global soil microbiome, and underscore the need to mitigate the spread of these co-resistant genes to safeguard public health.

Nitrophenyl Thiourea-Modified Polyethylenimine Colorimetric Sensor for Sulfate, Fluorine, and Acetate.

A thiourea-based colorimetric sensor incorporating polyethyleneimine (PEI) and chromophoric nitrophenyl groups was synthesized and utilized for detecting various anions. Structural characterization of the sensor was accomplished using FTIR and 1H-NMR spectroscopy. The sensor's interactions and colorimetric recognition capabilities with different anions, including CI-, Br-, I-, F-, NO3-, PF6-, AcO-, H2PO4-, PO43-, and SO42-, were investigated via visual observation and UV/vis spectroscopy. Upon adding SO42-, F-, and AcO- anions, the sensor exhibited distinct color changes from colorless to yellow and yellowish, while other anions did not induce significant color alterations. UV/vis spectroscopic titration experiments conducted in a DMSO/H2O solution (9:1 volume ratio) demonstrated the sensor's selectivity toward SO42-, F-, and AcO-. The data revealed that the formation of the main compounds and anion complexes was mediated by hydrogen bonding, leading to signal changes in the nitrophenyl thiourea-modified PEI spectrum.

Screening of plant growth-promoting rhizobacteria helps alleviate the joint toxicity of PVC+Cd pollution in sorghum plants.

Combined microplastic and heavy metal pollution (CM-HP) has become a popular research topic due to the ability of these pollutants to have complex interactions. Plant growth-promoting rhizobacteria (PGPR) are widely used to alleviate stress from heavy metal pollution in plants. However, the effects and mechanisms by which these bacteria interact under CM-HP have not been extensively studied. In this study, we isolated and screened PGPR from CM-HP soils and analyzed the effects of these PGPR on sorghum growth and Cd accumulation under combined PVC+Cd pollution through pot experiments. The results showed that the length and biomass of sorghum plants grown in PVC+Cd contaminated soil were significantly lower than those grown in soils contaminated with Cd alone, revealing an enhancement in toxicity when the two contaminants were mixed. Seven isolated and screened PGPR strains effectively alleviated stress due to PVC+Cd contamination, which resulted in a significant enhancement in sorghum biomass. PGPR mitigated the decrease in soil available potassium, available phosphorus and alkali-hydrolyzable nitrogen content caused by combined PVC+Cd pollution and increased the contents of these soil nutrients. Soil treatment with combined PVC+Cd pollution and PGPR inoculation can affect rhizosphere bacterial communities and change the composition of dominant populations, such as Proteobacteria, Firmicutes, and Actinobacteria. PICRUSt2 functional profile prediction revealed that combined PVC+Cd pollution and PGPR inoculation affected nitrogen fixation, nitrification, denitrification, organic phosphorus mineralization, inorganic phosphorus solubilization and the composition and abundance of genes related the N and P cycles. The Mantel test showed that functional strain abundance, the diversity index and N and P cycling-related genes were affected by test strain inoculation and were significant factors affecting sorghum growth, Cd content and accumulation. This study revealed that soil inoculation with isolated and screened PGPR can affect the soil inorganic nutrient content and bacterial community composition, thereby alleviating the stress caused by CM-HP and providing a theoretical basis and data support for the remediation of CM-HP.

Thyroid disorders and gastrointestinal dysmotility: an old association.

Gastrointestinal motility symptoms may be closely related to thyroid diseases. Sometimes, such symptoms are the only thyroid disease-related clue although the degree of the symptoms may vary. The exact mechanism of action of thyroid hormones on gastrointestinal motility is not completely understood, however, a clue lies in the fact that muscle cell receptors can be directly acted upon by thyroxines. Both hypo- and hyperthyroidism can cause impairment of gastrointestinal motility, modifying structure and function of pharynx and esophagus, and regulating esophageal peristalsis through neuro-humoral interaction. In hyperthyroid patients, alterations of postprandial and basic electric rhythms have been observed at gastro-duodenal level, often resulting in slower gastric emptying. Gastric emptying may also be delayed in hypothyroidism, but an unrelated gastric mucosa-affecting chronic modification may also cause such pattern. Hyperthyroidism commonly show malabsorption and diarrhoea, while hypothyroidism frequently show constipation. In summary, it can be stated that symptoms of gastrointestinal motility dysfunction can be related to thyroid diseases, affecting any of the gastrointestinal segment. Clinically, the typical thyroid disease manifestations may be missing, borderline, or concealed because of intercurrent sicknesses. Motility-linked gastrointestinal problems may easily conceal a misdetected, underlying dysthyroidism that should be carefully analyzed. Here, we aim to elaborate on the associations between thyroid disorders and GI dysmotility and the common clinical manifestations associated with GI dysmotility.

Nuclear matrix protein 22 in bladder cancer.

Bladder cancer (BC) is ranked as the ninth most common malignancy worldwide, with approximately 570,000 new cases reported annually and over 200,000 deaths. Cystoscopy remains the gold standard for the diagnosis of BC, however, its invasiveness, cost, and discomfort have driven the demand for the development of non-invasive, cost-effective alternatives. Nuclear matrix protein 22 (NMP22) is a promising non-invasive diagnostic tool, having received FDA approval. Traditional methods for detecting NMP22 require a laboratory environment equipped with specialized equipment and trained personnel, thus, the development of NMP22 detection devices holds substantial potential for application. In this review, we evaluate the NMP22 sensors developed over the past decade, including electrochemical, colorimetric, and fluorescence biosensors. These sensors have enhanced detection sensitivity and overcome the limitations of existing diagnostic methods. However, many emerging devices exhibit deficiencies that limit their potential clinical use, therefore, we propose how sensor design can be optimized to enhance the likelihood of clinical translation and discuss the future applications of NMP22 as a legacy biomarker, providing insights for the design of new sensors.