Diagnoses and Treatment of Acquired Undescended Testes: A Review.

Acquired undescended testes were once considered a sporadic disease. In recent years, reports suggest that they are not uncommon, with an incidence rate about 3 times that of congenital undescended testes. The etiology of acquired undescended testes remains inconclusive, clinical diagnostic standards are unclear, and treatment approaches are still controversial. There is ongoing debate about the mechanism of testicular ascent. The prevailing view is that acquired undescended testes occur due to the partial absorption of the gubernaculum, which forms part of the parietal peritoneum. The residual gubernacular fibers continuously pull on the spermatic cord, preventing the spermatic cord from elongating proportionately to somatic growth, leading to a re-ascent of the testis. Acquired undescended testes may increase the risk of testicular cancer, but this is still debated. The preferred treatment method is also controversial. However, surgical fixation has an immediate effect; no studies have proven that early surgery improves fertility in patients. The etiology of acquired undescended testes is closely related to the continuous pull of the residual gubernacular fibers on the spermatic cord, which prevents the cord from extending proportionately to body growth. There are no clear diagnostic standards for acquired undescended testes yet, and spontaneous descent is possible, so testicular fixation surgery may not be the preferred treatment method.

5-year Long-term Outcome of Unilateral Cleft Rhinoplasty in Patients with Secondary Nasal Deformity: Optimal Indication of Tajima Technique.

BACKGROUND: This study aimed to investigate the timing of and indications for the Tajima reverse U incision for correcting secondary unilateral cleft nasal deformities. METHODS: Non-syndromic patients with secondary cleft lip and nasal deformity who received Tajima reverse-U incision rhinoplasty were grouped by age (4-13 years, n=56;13-18 years, n=22; >18 years, n=18) and severity of deformity (mild deformity, n=7; moderate deformity=22; severity deformity=67) during 5-year follow-up. Face-Q assessment, a rating scale, and nasal symmetry measurements were employed in this study. RESULTS: Ninety-six patients completed the FACE-Q assessment for the nose and nostril. The results showed higher satisfaction with nostril appearance 1-week after surgery (85.95±13.01) compared with pre-operation (79.72±11.89) and maintained 5-year follow-up (82.61±14.06). Significant differences were observed in five nasal parameters (nasal height ratio, one-fourth media part of nostril height ratio, nasal sill height ratio, columellar angle, and inner nostril height-to-width ratio (cleft)) for 1-week postoperatively and the corrected outcome of the Tajima technique was maintained 5 years after surgery in aged 4-13 years group. The same statistically significant changes were found in nasal sill height ratio in mild deformity group and nostril width ratio, one-fourth media part of nostril height ratio, columellar angle, and inner nostril height-to-width ratio (cleft) in moderate deformity group. CONCLUSION: The Tajima procedure was beneficial for preadolescent children and children with mild to moderate unilateral cleft nasal deformities.

Promotion of perineural invasion of cholangiocarcinoma by Schwann cells via nerve growth factor.

Background: Cholangiocarcinoma (CCA), a highly lethal tumor of the hepatobiliary system originating from bile duct epithelium, can be divided into the intrahepatic, hilar, and extrahepatic types. Due to its insidious onset and atypical early clinical symptoms, the overall prognosis is poor. One of the important factors contributing to the poor prognosis of CCA is the occurrence of perineural invasion (PNI), but the specific mechanisms regarding how it contributes to the occurrence of PNI are still unclear. The main purpose of this study is to explore the molecular mechanism leading to the occurrence of PNI and provide new ideas for clinical treatment. Methods: CCA cell lines and Schwann cells (SCs) were stimulated to observe the changes in cell behavior. SCs cocultured with tumor supernatant and SCs cultured in normal medium were subjected to transcriptome sequencing to screen the significantly upregulated genes. Following this, the two types of tumor cells were cultured with SC supernatant, and the changes in behavior of the tumor cells were observed. Nonobese diabetic-severe combined immunodeficiency disease (NOD-SCID) mice were injected with cell suspension supplemented with nerve growth factor (NGF) via the sciatic nerve. Four weeks later, the mice were euthanized and the tumor sections were removed and stained. Results: Nerve invasion by tumor cells was common in CCA tissues. SCs were observed in tumor tissues, and the number of SCs in tumor tissues and the degree of PNI were much higher than were those in normal tissues or tissues without PNI. The overall survival time was shorter in patients with CCA with PNI than in patients without PNI. SCs were enriched in CCA tissues, indicating the presence of PNI and associated with poor prognosis in CCA patients. CCA was found to promote NGF secretion from SCs in vitro. After the addition of exogenous NGF in CCA cell culture medium, the proliferation activity and migration ability of CCA cells were significantly increased, suggesting that SCs can promote the proliferation and migration of CCA through the secretion of NGF. NGF, in turn, was observed to promote epithelial-mesenchymal transition in CCA through tropomyosin receptor kinase A (TrkA), thus promoting its progression. Tumor growth in mice shows that NGF can promote PNI in CCA. Conclusions: In CCA, tumor cells can promote the secretion of NGF by SCs, which promotes the progression of CCA and PNI by binding to its high-affinity receptor TrkA, leading to poor prognosis.

Effects of protein-glutaminase on the properties of glutinous rice flour, paste, and gel food: Based on the interactions between the deamidated protein and starch.

In the present study, protein-glutaminase (PG) from Chryseobacterium proteolyticum was applied to improve the processing properties of glutinous rice flour (GRF). After PG modification, the degree of deamidation of glutinous rice protein (GRP) reached 13.6% at 2.0 h, with smaller particle size and decreased zeta potential. The interaction of GRP with starch in PG-modified GRF (PM-GRF) was changed, exhibiting in protein aggregates decreasing and exposure of starch on the surface of GRF. Compared with unmodified GRF (UM-GRF), the solubility and turbidity of PM-GRF were both increased. The rheological properties reflected that the viscosity of PM-GRF paste was increased, and the freeze-thaw stability was also enhanced. Moreover, the textural characteristics showed that the hardness of PM-GRF balls remarkably reduced and the springiness increased. These results indicate that deamidation by PG could be an efficient method for improving characteristics of GRP and GRF.

Phosphoribosylpyrophosphate synthetase as a metabolic valve advances Methylobacterium/Methylorubrum phyllosphere colonization and plant growth.

The proficiency of phyllosphere microbiomes in efficiently utilizing plant-provided nutrients is pivotal for their successful colonization of plants. The methylotrophic capabilities of Methylobacterium/Methylorubrum play a crucial role in this process. However, the precise mechanisms facilitating efficient colonization remain elusive. In the present study, we investigate the significance of methanol assimilation in shaping the success of mutualistic relationships between methylotrophs and plants. A set of strains originating from Methylorubrum extorquens AM1 are subjected to evolutionary pressures to thrive under low methanol conditions. A mutation in the phosphoribosylpyrophosphate synthetase gene is identified, which converts it into a metabolic valve. This valve redirects limited C1-carbon resources towards the synthesis of biomass by up-regulating a non-essential phosphoketolase pathway. These newly acquired bacterial traits demonstrate superior colonization capabilities, even at low abundance, leading to increased growth of inoculated plants. This function is prevalent in Methylobacterium/Methylorubrum strains. In summary, our findings offer insights that could guide the selection of Methylobacterium/Methylorubrum strains for advantageous agricultural applications.

Fracture-driven power amplification in a hydrogel launcher.

Robotic tasks that require robust propulsion abilities such as jumping, ejecting or catapulting require power-amplification strategies where kinetic energy is generated from pre-stored energy. Here we report an engineered accumulated strain energy-fracture power-amplification method that is inspired by the pressurized fluidic squirting mechanism of Ecballium elaterium (squirting cucumber plants). We realize a light-driven hydrogel launcher that harnesses fast liquid vapourization triggered by the photothermal response of an embedded graphene suspension. This vapourization leads to appreciable elastic energy storage within the surrounding hydrogel network, followed by rapid elastic energy release within 0.3 ms. These soft hydrogel robots achieve controlled launching at high velocity with a predictable trajectory. The accumulated strain energy-fracture method was used to create an artificial squirting cucumber that disperses artificial seeds over metres, which can further achieve smart seeding through an integrated radio-frequency identification chip. This power-amplification strategy provides a basis for propulsive motion to advance the capabilities of miniaturized soft robotic systems.

Mining for QTL controlling maize low-phosphorus response genes combined with deep resequencing of RIL parental genomes and in silico GWAS analysis.

KEY MESSAGE: Extensive and comprehensive phenotypic data from a maize RIL population under both low- and normal-Pi treatments were used to conduct QTL mapping. Additionally, we integrated parental resequencing data from the RIL population, GWAS results, and transcriptome data to identify candidate genes associated with low-Pi stress in maize. Phosphorus (Pi) is one of the essential nutrients that greatly affect the maize yield. However, the genes underlying the QTL controlling maize low-Pi response remain largely unknown. In this study, a total of 38 traits at both seedling and maturity stages were evaluated under low- and normal-Pi conditions using a RIL population constructed from X178 (tolerant) and 9782 (sensitive), and most traits varied significantly between low- and normal-Pi treatments. Twenty-nine QTLs specific to low-Pi conditions were identified after excluding those with common intervals under both low- and normal-Pi conditions. Furthermore, 45 additional QTLs were identified based on the index value ((Trait_under_LowPi-Trait_under_NormalPi)/Trait_under_NormalPi) of each trait. These 74 QTLs collectively were classified as Pi-dependent QTLs. Additionally, 39 Pi-dependent QTLs were clustered in nine HotspotQTLs. The Pi-dependent QTL interval contained 19,613 unique genes, 6,999 of which exhibited sequence differences with non-synonymous mutation sites between X178 and 9782. Combined with in silico GWAS results, 277 consistent candidate genes were identified, with 124 genes located within the HotspotQTL intervals. The transcriptome analysis revealed that 21 genes, including the Pi transporter ZmPT7 and the strigolactones pathway-related gene ZmPDR1, exhibited consistent low-Pi stress response patterns across various maize inbred lines or tissues. It is noteworthy that ZmPDR1 in maize roots can be sharply up-regulated by low-Pi stress, suggesting its potential importance as a candidate gene for responding to low-Pi stress through the strigolactones pathway.

Blocking ß2-AR and Inhibiting COX-2: A Promising Approach to Suppress OSCC Development.

OBJECTIVES: ß2-adrenergic receptor (ß2-AR) and cyclooxygenase-2 (COX-2) are overexpressed in various malignant tumours including oral squamous cell carcinoma (OSCC), suggesting that they may contribute to the development of OSCC. This study aims to investigate the potential synergistic effect of ß2-AR blockade and COX-2 inhibition on suppressing the development of OSCC. METHODS: Effects of blocking ß2-AR and inhibiting COX-2 on migration and invasion of OSCC cells were detected by wound-healing assay and transwell invasion assay. Western blot and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of genes related to the progression of OSCC. In vivo, OSCC xenograft models were established to evaluate the effect of combined treatment on survival time, tumour size, and submandibular lymph node metastasis. Immunohistochemistry, Western blot, and ELISA were used to detect the expression of invasion and metastasis relative genes. RESULTS: In vitro, blocking ß2-AR or inhibiting COX-2 alone could suppress invasion and metastasis of OSCC cells, and suppression with combined treatment was more significant. Expression of genes related to invasion and metastasis, including EGFR, TGF-ß1, IL-1ß, MMP2, and VEGFA, were downregulated significantly, especially in the combined treatment group. In vivo, the combined treatment could significantly prolong survival time in tumour-bearing mice and inhibit the growth of tumours. Furthermore, submandibular lymph node metastasis was less in the combined treatment group, and expression of the abovementioned genes was also downregulated. CONCLUSIONS: The combination of ß2-AR blockade and COX-2 inhibition can significantly suppress the development of OSCC via downregulating EGFR, TGF-ß1, IL-1ß, MMP2, and VEGFA. Findings suggest that the combined use of a ß2-AR blocker and a COX-2 inhibitor could be a promising adjuvant therapy in OSCC. Both drugs are commonly prescribed, and their safety and efficacy are well established. Their use in adjuvants in OSCC should therefore be promoted in clinical practice.

Discovery of Fluorescent Naturally-occurring Inhibitor of SARS-CoV-2 Main Protease By AIE Fluorescent Probe.

Target-based high-throughput screening (HTS) is an efficient way to identify potent drugs. However, the accuracy of HTS could be affected by Pan-Assay Interference Compounds (PAINS). One reason for the generation of PAINS is that the inherent photophysical property of screened compounds could interfere with typically used assay signals including absorption and fluorescence. Our previous studies indicate that the fluorescent probe based on the fluorophore with characteristics of aggregation-induced emission (AIE) could provide high accuracy of HTS, especially for the fluorescent natural products. Herein, we report an AIE-based fluorescent probe for the main protease (Mpro) of SARS-CoV-2. We designed and synthesized an AIE fluorescent probe ZLHG5, which has a site that can be specifically cleaved by Mpro to produce a light-up fluorescence. Thanks to the large Stokes shift of AIE fluorophore (~300 nm), the probe could be effectively used for HTS of Mpro inhibitors. After screening a library of fluorescent natural products with ZLHG5, we obtained two coumarin-originated natural compounds with potent inhibitory activity towards Mpro protease. This study provides both useful fluorescent HTS probe and potent inhibitors for Mpro protease.

An injectable and coagulation-independent Tetra-PEG hydrogel bioadhesive for post-extraction hemostasis and alveolar bone regeneration.

Effective control of post-extraction hemorrhage and alveolar bone resorption is critical for successful extraction socket treatment, which remains an unmet clinical challenge. Herein, an injectable Tetra-PEG hydrogel that possesses rapid gelation, firm tissue adhesion, high mechanical strength, suitable degradability, and excellent biocompatibility is developed as a sutureless and coagulation-independent bioadhesive for the management of extraction sockets. Our results demonstrate that the rapid and robust adhesive sealing of the extraction socket by the Tetra-PEG hydrogel can provide reliable protection for the underlying wound and stabilize blood clots to facilitate tissue healing. In vivo experiments using an anticoagulated rat tooth extraction model show that the hydrogel significantly outperformed clinically used cotton and gelatin sponge in hemostatic efficacy, wound closure, alveolar ridge preservation, and in situ alveolar bone regeneration. Histomorphological evaluations reveal the mechanisms for accelerated bone repair through suppressed long-term inflammation, elevated collagen deposition, higher osteoblast activity, and enhanced angiogenesis. Together, our study highlights the clinical potential of the developed injectable Tetra-PEG hydrogel for treating anticoagulant-related post-extraction hemorrhage and improving socket healing.

A heterogeneous tumor immune microenvironment of uncommon epidermal growth factor receptor mutant non-small cell lung cancer.

Common epidermal growth factor receptor (EGFR) mutations are usually not considered for immunotherapy in non-small cell lung cancer (NSCLC) due to poor efficacy. However, whether uncommon EGFR mutations are suitable for immunotherapy has not been thoroughly studied. Thus, we explored the tumor immune microenvironment (TME) features in uncommon EGFR mutant NSCLC. In this study, a total of 41 patients with EGFR mutations were included, the majority (85.4%) of whom were stage I. Among them, 22 patients harbored common mutations, while 19 patients presented with uncommon mutations. Compared with common mutations, uncommon mutations exhibited more infiltrating T cells and fewer M2 macrophages, upregulated expression of antigen processing and a presentation pathway. Unsupervised clustering based on the mIF profile identified two classes with heterogeneous TME in uncommon mutations. Class 1 featured the absence of PD-1+ cytotoxic T cell infiltration, and class 2 displayed a hotter TME because of the downregulated expression of hypoxia (p < 0.001), oxidative phosphorylation (p = 0.009), and transforming growth factor beta signaling (p = 0.01) pathways as well as increased expression of CTLA4 (p = 0.001) and PDCD1 (p = 0.004). The association of CTLA4 and PDCD1 with TME profiles was validated in a TCGA lung adenocarcinoma cohort with uncommon EGFR mutations. Our study reveals the distinct and heterogeneous TME features in uncommon EGFR mutant NSCLC.

An Injectable Hydrogel with Ultrahigh Burst Pressure and Innate Antibacterial Activity for Emergency Hemostasis and Wound Repair.

Uncontrolled bleeding and wound infections following severe trauma pose significant challenges for existing tissue adhesives, primarily due to their weak wet adhesion, slow adhesion formation, cytotoxicity concerns, and lack of antibacterial properties. Herein, an injectable hydrogel (denoted as ES gel) with rapid, robust adhesive sealing and inherent antibacterial activity based on ε-polylysine and a poly(ethylene glycol) derivative is developed. The engineered hydrogel exhibits rapid gelation behavior, high mechanical strength, strong adhesion to various tissues, and can sustain an ultrahigh burst pressure of 450 mmHg. It also presents excellent biocompatibility, biodegradability, antibacterial properties, and on-demand removability. Significantly improved hemostatic efficacy of ES gel compared to fibrin glue is demonstrated using various injury models in rats and rabbits. Remarkably, the adhesive hydrogel can effectively halt lethal non-compressible hemorrhages in visceral organs (liver, spleen, and heart) and femoral artery injury models in fully anticoagulated pigs. Furthermore, the hydrogel outperforms commercial products in sutureless wound closure and repair in the rat liver defect, skin incision, and infected full-thickness skin wound models. Overall, this study highlights the promising clinical applications of ES gel for managing uncontrolled hemorrhage, sutureless wound closure, and infected wound repair. This article is protected by copyright. All rights reserved.

An Advanced Tool Wear Forecasting Technique with Uncertainty Quantification Using Bayesian Inference and Support Vector Regression.

Tool wear prediction is of great significance in industrial production. Current tool wear prediction methods mainly rely on the indirect estimation of machine learning, which focuses more on estimating the current tool wear state and lacks effective quantification of random uncertainty factors. To overcome these shortcomings, this paper proposes a novel method for predicting cutting tool wear. In the offline phase, the multiple degradation features were modeled using the Brownian motion stochastic process and a SVR model was trained for mapping the features and the tool wear values. In the online phase, the Bayesian inference was used to update the random parameters of the feature degradation model, and the future trend of the features was estimated using simulation samples. The estimation results were input into the SVR model to achieve in-advance prediction of the cutting tool wear in the form of distribution densities. An experimental tool wear dataset was used to verify the effectiveness of the proposed method. The results demonstrate that the method shows superiority in prediction accuracy and stability.

Direct Synthesis of α-Ketothioamide Derivatives through a One-Pot Reaction of Sulfur Ylides, Nitrosobenzenes, and Thioacetic Acid.

A one-pot approach has been developed for the synthesis of α-ketothioamide derivatives from sulfur ylides, nitrosobenzenes, and thioacetic acid. This protocol is carried out under mild reaction conditions in generally moderate to excellent yields without any precious catalysts, affording the derivatives with structural diversity. Additionally, a possible mechanism for this chemical transformation is proposed.

Impacts of transglutaminase on the processing and digestion characteristics of glutinous rice flour: Insight of the interactions between enzymic crossing-linked protein and starch.

Glutinous rice is extensively consumed due to its nutritious content and wonderful flavor. However, glutinous rice flour has a high glycemic index, and the storage deterioration of sweet dumplingsissevere. Transglutaminase (TG) was used to cross-link glutinous rice protein and improve the characteristics of glutinous rice products. The findings demonstrated that TG significantly catalysed protein cross-linking to form a dense protein network, reduced the viscosity of glutinous rice paste and improved the thermal stability. The protein network may physically block the access of starch granules to digestive enzymes to lower the digestion rate of starch, and attenuate the damage of ice crystal molecules to the starch structure to improve the freezing stability of starch gels. The cracking rate and water loss of sweet dumplings prepared using glutinous rice flour with TG treated for 60 min reduced significantly. In conclusion, this study broadened the application of TG in starch products.

Focused ultrasound enables selective actuation and Newton-level force output of untethered soft robots.

Untethered miniature soft robots have significant application potentials in biomedical and industrial fields due to their space accessibility and safe human interaction. However, the lack of selective and forceful actuation is still challenging in revolutionizing and unleashing their versatility. Here, we propose a focused ultrasound-controlled phase transition strategy for achieving millimeter-level spatially selective actuation and Newton-level force of soft robots, which harnesses ultrasound-induced heating to trigger the phase transition inside the robot, enabling powerful actuation through inflation. The millimeter-level spatial resolution empowers single robot to perform multiple tasks according to specific requirements. As a concept-of-demonstration, we designed soft robot for liquid cargo delivery and biopsy robot for tissue acquisition and patching. Additionally, an autonomous control system is integrated with ultrasound imaging to enable automatic acoustic field alignment and control. The proposed method advances the spatiotemporal response capability of untethered miniature soft robots, holding promise for broadening their versatility and adaptability.

POLR2J expression promotes glioblastoma malignancy by regulating oxidative stress and the STAT3 signaling pathway.

Glioblastoma is the most common cancer in the brain, resistant to conventional therapy and prone to recurrence. Therefore, it is crucial to explore novel therapeutics strategies for the treatment and prognosis of GBM. In this study, through analyzing online datasets, we elucidated the expression and prognostic value of POLR2J and its co-expressed genes in GBM patients. Functional experiments, including assays for cell apoptosis and cell migration, were used to explore the effects of POLR2J and vorinostat on the proliferation and migration of GBM cells. The highest overexpression of POLR2J, among all cancer types, was observed in GBM. Furthermore, high expression of POLR2J or its co-expressed genes predicted a poor outcome in GBM patients. DNA replication pathways were significantly enriched in the GBM clinical samples with high POLR2J expression, and POLR2J suppression inhibited proliferation and triggered cell cycle G1/S phase arrest in GBM cells. Moreover, POLR2J silencing activated the unfolded protein response (UPR) and significantly enhanced the anti-GBM activity of vorinostat by suppressing cell proliferation and inducing apoptosis. Additionally, POLR2J could interact with STAT3 to promote the metastatic potential of GBM cells. Our study identifies POLR2J as a novel oncogene in GBM progression and provides a promising strategy for the chemotherapeutic treatment of GBM.

[Feeding ecology of Chaeturichthys stigmatias during autumn in Haizhou Bay]. / 海州湾秋季矛尾虾虎鱼的摄食生态.

Research about feeding ecology of fish is important to understand individual behavior and population development, which is also the basic to analyze trophic structure and function of aquatic ecosystems. Chaetrichthys stigmatias is one of the key species in the Haizhou Bay fisheries ecosystem, which has critical ecological niche within the food web. In this study, we collected samples through bottom trawl surveys during the fall of 2018 in the Haizhou Bay, and analyzed the feeding ecology of C. stigmatias based on both stomach content analysis and stable isotope technology. The results showed that the primary diet groups for C. stigmatias were Ophiuroidea and Shrimp, including Ophiothrix marenzelleri, Ophiopholis mirabilis, Ophiura sarsii, Penaeidae, and Alpheus japonicus. The range of δ13C values of C. stigmatias was from -19.39‰ to -15.74‰, with an average value of (-18.07±0.87)‰, which had no significant correlation with body length. The range of δ15N values was from 8.16‰ to 12.86‰, with an average value of (10.14±1.51)‰, which was positively correlated with body length. The trophic level of C. stigmatias showed a positive relationship with body length, with an average value of (3.74±0.34) and a range value of 3.32 to 4.20 among different size groups. The contribution rates of different prey groups varied significantly. Based on the structural equation modeling, we found that the feeding intensity of C. stigmatias was primally influenced by body length, sea bottom salinity, sea bottom temperature, and water depth, with a particularly signi-ficant positive correlation with body length. The combination of stable isotope technology and stomach content analysis methods could contribute to comprehensive understanding on the feeding ecology of C. stigmatias, providing essential data and foundation for research on trophic structures and resource conservation in the Haizhou Bay ecosystem.

Genome-wide association studies dissect low-phosphorus stress response genes underling field and seedling traits in maize.

Phosphorus (P) is an essential element for plant growth, and its deficiency can cause decreased crop yield. This study systematically evaluated the low-phosphate (Pi) response traits in a large population at maturity and seedling stages, and explored candidate genes and their interrelationships with specific traits. The results revealed a greater sensitivity of seedling maize to low-Pi stress compared to that at maturity stage. The phenotypic response patterns to low-Pi stress at different stages were independent. Chlorophyll content was found to be a potential indicator for screening low-Pi-tolerant materials in the field. A total of 2900 and 1446 significantly associated genes at the maturity and seedling stages were identified, respectively. Among these genes, 972 were uniquely associated with maturity traits, while 330 were specifically detected at the seedling stage under low-Pi stress. Moreover, 768 and 733 genes were specifically associated with index values (low-Pi trait/normal-Pi trait) at maturity and seedling stage, respectively. Genetic network diagrams showed that the low-Pi response gene Zm00001d022226 was specifically associated with multiple primary P-related traits under low-Pi conditions. A total of 963 out of 2966 genes specifically associated with traits under low-Pi conditions or index values were found to be induced by low-Pi stress. Notably, ZmSPX4.1 and ZmSPX2 were sharply up-regulated in response to low-Pi stress across different lines or tissues. These findings advance our understanding of maize's response to low-Pi stress at different developmental stages, shedding light on the genes and pathways implicated in this response.

UBA5 inhibition restricts lung adenocarcinoma via blocking macrophage M2 polarization and cisplatin resistance.

UBA5, a ubiquitin-like activated enzyme involved in ufmylation and sumoylation, presents a viable target for pancreatic and breast cancer treatments, yet its role in lung adenocarcinoma (LUAD) remains underexplored. This study reveals UBA5's tumor-promoting effect in LUAD, as evidenced by its upregulation in patients and positive correlation with TNM stages. Elevated UBA5 levels predict poor outcomes for these patients. Pharmacological inhibition of UBA5 using DKM 2-93 significantly curtails the growth of A549, H1299, and cisplatin-resistant A549 (A549/DDP) LUAD cells in vitro. Additionally, UBA5 knockdown via shRNA lentivirus suppresses tumor growth both in vitro and in vivo. High UBA5 expression adversely alters the tumor immune microenvironment, affecting immunostimulators, MHC molecules, chemokines, receptors, and immune cell infiltration. Notably, UBA5 expression correlates positively with M2 macrophage infiltration, the predominant immune cells in LUAD. Co-culture experiments further demonstrate that UBA5 knockdown directly inhibits M2 macrophage polarization and lactate production in LUAD. Moreover, in vivo studies show reduced M2 macrophage infiltration following UBA5 knockdown. UBA5 expression is also associated with increased tumor heterogeneity, including tumor mutational burden, microsatellite instability, neoantigen presence, and homologous recombination deficiency. Experiments indicate that UBA5 overexpression promotes cisplatin resistance in vitro, whereas UBA5 inhibition enhances cisplatin sensitivity in both in vitro and in vivo settings. Overall, these findings suggest that targeting UBA5 inhibits LUAD by impeding cancer cell proliferation, M2 macrophage polarization, and cisplatin resistance.