Suppression of SENP3 enhances macrophage alternative activation by mediating IRF4 de-SUMOylation in ESCC progression.

Esophageal cancer is common worldwide, with ESCC being the most frequent tumor in East Asia. Tumor-associated macrophages are an important component of the ESCC microenvironment. SUMOylation is a post-translational modification of proteins, and SUMO-specific proteases (SENPs) play an important role in de-SUMOylation. In human patients, we discovered that the levels of SENP3 were upregulated in the tumor-associated macrophages. Furthermore, the loss of SENP3 enhanced the alternative activation of macrophages in the 4-NQO-induced ESCC mice model. This is the first study to identify SENP3-mediated macrophage polarization via the de-SUMOylation of interferon regulatory factor 4 (IRF4) at the K349 site. Alternative activation of macrophages increases the migration and invasion potential of ESCC cells and promotes their progression in vivo. Moreover, patients with relatively low SENP3 expression in macrophages exhibit higher primary PET SUVmax value and lymph node metastasis rates. In summary, this study revealed that SENP3-mediated IRF4 de-SUMOylation is crucial for the alternative activation of macrophages and influences the progression of ESCC.

Overcoming High-Quality Limitations in Plasmonic Metasurfaces for Ultrasensitive Terahertz Applications.

In photonics, achieving high-quality (Q) resonance is crucial for high-sensitivity devices used in applications, such as switching, sensing, and lasing. However, high-Q resonances are highly susceptible to internal losses of plasmonic devices, impeding their integration into broader systems across terahertz and visible light bands. Here, we overcome this challenge by proposing a low-Q plasmonic metasurface for ultrasensitive terahertz (THz) switching and sensing. Theoretically, we reveal an approach to constructing a low-Q resonator possessing high sensitivity to nonradiative losses. Leveraging this mechanism, we design a highly sensitive plasmonic metasurface induced by strong coupling between a quasi-bound state in the continuum and a dipole mode. By hybridizing with the germanium layer, the metadevice exhibits an ultralow pump threshold of 192 µJ/cm2 and an ultrafast switching cycle time of 7 ps. Furthermore, it also shows a high sensitivity of 224 GHz/RIU in refractive index sensing. The proposed paradigm of constructing low-Q and high-sensitivity photonic devices can be applied to biosensing, wide-band filters, and sensitive modulators.

On-chip silicon photonic micro-ring processor lights up optical image encryption.

Optical image encryption has long been an important concept in the fields of photonic network processing and communication. Here, we propose a convolution-like operation-based optical image encryption algorithm exploiting a silicon photonic multiplexing architecture to achieve content security. Particularly, the encryption process is completed in a 3 × 3 cross-shaped photonic micro-ring resonator (MRR) array on chip. For the first time, to the best of our knowledge, this algorithm encodes information in an integrated intensity modulation, effectively reducing the encoding difficulty. Moreover, the high reliability and scalability of optical encryption are ensured using both linear and nonlinear operations on photonic chips according to characteristics of MRRs. As the encryption and decryption experiments show, the image restoration accuracy of our optical encryption algorithm exceeds 99% under real system noise at the pixel level, indicating its noise-robust property. Meanwhile, the peak signal-to-noise ratios of the restored and encrypted images are >60 and <15 dB, respectively, revealing both the high accuracy of the restored image and the small correlation between the encrypted and original images. This work adds to the rapidly expanding field of optical image encryption on photonic chips.

Atomic Layer Deposition of TiO2 on Si Window Enables In Situ ATR-SEIRAS Measurements in Strong Alkaline Electrolytes.

The Si window is the most widely used internal reflection element (IRE) for electrochemical attenuated total reflection surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS), yet local chemical etching on Si by concentrated OH- anions bottlenecks the reliable application of this method in strong alkaline electrolytes. In this report, atomic layer deposition of a 25 nm nonconductive TiO2 barrier layer on the reflecting plane of a Si prism is demonstrated to address this challenge. In situ ATR-SEIRAS measurement on a Au film electrode with the Si/TiO2 composite IRE in 1 M NaOH reveals reversible global spectral features without spectral distortion at 1000-1300 cm-1, in stark contrast to those obtained with a bare Si window. By applying this structured ATR-SEIRAS, ethanol electrooxidation on a Pt/C catalyst in 1 and 5 M NaOH is explored, manifesting that such high pH values prevent the adsorption of as-formed acetate in the C2 pathway but not that of CO intermediate in the C1 pathway.

PA200-Mediated Proteasomal Protein Degradation and Regulation of Cellular Senescence.

Cellular senescence is closely related to DNA damage, proteasome inactivity, histone loss, epigenetic alterations, and tumorigenesis. The mammalian proteasome activator PA200 (also referred to as PSME4) or its yeast ortholog Blm10 promotes the acetylation-dependent degradation of the core histones during transcription, DNA repair, and spermatogenesis. According to recent studies, PA200 plays an important role in senescence, probably because of its role in promoting the degradation of the core histones. Loss of PA200 or Blm10 is a major cause of the decrease in proteasome activity during senescence. In this paper, recent research progress on the association of PA200 with cellular senescence is summarized, and the potential of PA200 to serve as a therapeutic target in age-related diseases is discussed.

PTEN status determines therapeutic vulnerability to celastrol in cholangiocarcinoma.

BACKGROUND: A balanced protein homeostasis network helps cholangiocarcinoma (CCA) maintain their oncogenic growth, and disrupting proteostasis therapeutically will induce proteotoxic stress. Phosphatase and tensin homolog (PTEN) have been reported to be involved in proteostasis, and PTEN-associated pathways are commonly altered in CCA. Celastrol, a triterpene from plants, exhibits cytotoxic effects in various types of cancer. However, the underlying mechanisms remain unclear. PURPOSE: We investigated the therapeutic effect of celastrol in CCA and identified the molecular characteristics of tumors that were sensitive to celastrol. The target of celastrol was explored. We then evaluated the candidate combination therapeutic strategy to increase the effectiveness of celastrol in celastrol-insensitive CCA tumors. METHODS: Various CCA cells were categorized as either celastrol-sensitive or celastrol-insensitive based on their response to celastrol. The molecular characteristics of cells from different groups were determined by RNA-seq. PTEN status and its role in proteasome activity in CCA cells were investigated. The CMAP analysis, molecular docking, and functional assay were performed to explore the effect of celastrol on proteasome activities. The correlation between PTEN status and clinical outcomes, as well as proteasomal activity, were measured in CCA patients. The synergistic therapeutic effect of autophagy inhibitors on celastrol-insensitive CCA cells were measured. RESULTS: Diverse responses to celastrol were observed in CCA cells. PTEN expression varied among different CCA cells, and its status could impact cell sensitivity to celastrol: PTENhigh tumor cells were resistant to celastrol, while PTENlow cells were more sensitive. Celastrol induced proteasomal dysregulation in CCA cells by directly targeting PSMB5. Cells with low PTEN status transcriptionally promoted proteasome subunit expression in an AKT-dependent manner, making these cells more reliant on proteasomal activities to maintain proteostasis. This caused the PTENlow CCA cells sensitive to celastrol. A negative correlation was found between PTEN levels and the proteasome signature in CCA patients. Moreover, celastrol treatment could induce autophagy in PTENhigh CCA cells. Disrupting the autophagic pathway in PTENhigh CCA cells enhanced the cytotoxic effect of celastrol. CONCLUSION: PTEN status in CCA cells determines their sensitivity to celastrol, and autophagy inhibitors could enhance the anti-tumor effect in PTENhigh CCA.

Perioperative outcomes and survival after neoadjuvant immunochemotherapy for locally advanced esophageal squamous cell carcinoma.

OBJECTIVE: This study aimed to compare the difference in perioperative outcomes and prognosis between neoadjuvant immunochemotherapy and neoadjuvant chemoradiotherapy for locally advanced esophageal squamous cell carcinoma. METHODS: The patients with locally advanced esophageal squamous cell carcinoma receiving neoadjuvant immunochemotherapy or neoadjuvant chemoradiotherapy were identified from a prospectively maintained database at Zhongshan Hospital of Fudan University between January 2018 and March 2022. Propensity score matching was performed to balance the 2 groups. RESULTS: A total of 124 patient pairs were enrolled in the final analysis. The complete pathological response rate (20.2% vs 29.0%, P = .140) was similar in the 2 groups, whereas the lower major pathological response rate (44.4% vs 61.3%, P = .011) was observed in the neoadjuvant immunochemotherapy group. Neoadjuvant immunochemotherapy was associated with a lower rate of adverse events (42.7% vs 55.6%, P = .047) without additional postoperative complications (38.7% vs 35.5%, P = .693). The neoadjuvant immunochemotherapy group had lower distant metastasis (6.5% vs 16.1%, P = .027) and overall recurrence (11.3% vs 23.4%, P = .019) in the postoperative 1 year. Also, neoadjuvant immunochemotherapy was associated with better progression-free survival (hazard ratio, 0.50; 95% CI, 0.32-0.77; P = .002). Cox proportional hazard analysis showed that neoadjuvant immunochemotherapy (univariable: hazard ratio, 0.55; 95% CI, 0.37-0.82; P = .003; multivariable: hazard ratio, 0.44; 95% CI, 0.29-0.65; P < .001) was one of the independent prognostic factors for progression-free survival. The 2 groups had similar overall survival (hazard ratio, 0.62; 95% CI, 0.36-1.09; P = .094) at the latest follow-up. CONCLUSIONS: This retrospective study showed that neoadjuvant immunochemotherapy was safe and effective for patients with locally advanced esophageal squamous cell carcinoma. Further verification is needed in randomized controlled trials.

Color coded metadevices toward programmed terahertz switching.

Terahertz modulators play a critical role in high-speed wireless communication, non-destructive imaging, and so on, which have attracted a large amount of research interest. Nevertheless, all-optical terahertz modulation, an ultrafast dynamical control approach, remains to be limited in terms of encoding and multifunction. Here we experimentally demonstrated an optical-programmed terahertz switching realized by combining optical metasurfaces with the terahertz metasurface, resulting in 2-bit dual-channel terahertz encoding. The terahertz metasurface, made up of semiconductor islands and artificial microstructures, enables effective all-optical programming by providing multiple frequency channels with ultrafast modulation at the nanosecond level. Meanwhile, optical metasurfaces covered in terahertz metasurface alter the spatial light field distribution to obtain color code. According to the time-domain coupled mode theory analysis, the energy dissipation modes in terahertz metasurface can be independently controlled by color excitation, which explains the principle of 2-bit encoding well. This work establishes a platform for all-optical programmed terahertz metadevices and may further advance the application of composite metasurface in terahertz manipulation.

Association between negative life events through mental health and non-suicidal self-injury with young adults: evidence for sex moderate correlation.

BACKGROUND: Non-suicidal self-injury (NSSI) has exhibited an increasing trend in recent years and is now globally recognized as a major public health problem among adolescents and young adults. Negative life events (NLEs) are positively associated with NSSI. We sought to explore (1) whether sex plays a role in the risk of NLEs leading to NSSI and (2) the role played by mental health (MH). METHODS: We adopted a multi-stage cluster sampling method to select college students across four grades from May to June 2022. Generalized linear models were used to evaluate the relationships between NLEs, sex, MH and NSSI, presented as incidence-rate ratios (RRs) with 95% confidence intervals (CIs). We examined the complex relationship between these variables using the PROCESS method for moderation analysis. RESULTS: Following the exclusion of data that did not meet the study requirements, data from 3,578 students (mean age: 20.53 [± 1.65] years) were included. Poisson regression results indicate that high-level NLEs (RR = 0.110, 95%CI: 0.047-0.173) are associated with increased NSSI. Furthermore, interaction effects were observed among sex, NLEs and NSSI. MH and sex moderated the relationship between NLEs and NSSI. CONCLUSION: Identifying risk factors for NSSI is also important when exploring the interaction between NLEs and MH given the potential for NSSI to significantly increase the risk of later psychopathological symptoms and substance abuse problems. In addition, the significance of sex differences in risk factors for NSSI should be determined. This study evaluated how the impact of NLEs on NSSI can be reduced among adolescents from multiple perspectives.

Creating Anti-Chiral Exceptional Points in Non-Hermitian Metasurfaces for Efficient Terahertz Switching.

Non-Hermitian degeneracies, also known as exceptional points (EPs), have presented remarkable singular characteristics such as the degeneracy of eigenvalues and eigenstates and enable limitless opportunities for achieving fascinating phenomena in EP photonic systems. Here, the general theoretical framework and experimental verification of a non-Hermitian metasurface that holds a pair of anti-chiral EPs are proposed as a novel approach for efficient terahertz (THz) switching. First, based on the Pancharatnam-Berry (PB) phase and unitary transformation, it is discovered that the coupling variation of ±1 spin eigenstates will lead to asymmetric modulation in two orthogonal linear polarizations (LP). Through loss-induced merging of a pair of anti-chiral EPs, the decoupling of ±1 spin eigenstates are then successfully realized in a non-Hermitian metasurface. Final, the efficient THz modulation is experimentally demonstrated, which exhibits modulation depth exceeding 70% and Off-On-Off switching cycle less than 9 ps in one LP while remains unaffected in another one. Compared with conventional THz modulation devices, the metadevice shows several figures of merits, such as a single frequency operation, high modulation depth, and ultrafast switching speed. The proposed theory and loss-induced non-Hermitian device are general and can be extended to numerous photonic systems varying from microwave, THz, infrared, to visible light.

Plastome structure, phylogeny and evolution of plastid genes in Reevesia (Helicteroideae, Malvaceae).

Reevesia is an eastern Asian-eastern North American disjunction genus in the family Malvaceae s.l. and comprises approximately 25 species. The relationships within the genus are not well understood. Here, 15 plastomes representing 12 Reevesia species were compared, with the aim of better understanding the species circumscription and phylogenetic relationships within the genus and among genera in the family Malvaceae s.l. The 11 newly sequenced plastomes range between 161,532 and 161, 945 bp in length. The genomes contain 114 unique genes, 18 of which are duplicated in the inverted repeats (IRs). Gene content of these plastomes is nearly identical. All the protein-coding genes are under purifying selection in the Reevesia plastomes compared. The top ten hypervariable regions, SSRs, and the long repeats identified are potential molecular markers for future population genetic and phylogenetic studies. Phylogenetic analysis based on the whole plastomes confirmed the monophyly of Reevesia and a close relationship with Durio (traditional Bombacaceae) in subfamily Helicteroideae, but not with the morphologically similar genera Pterospermum and Sterculia (both of traditional Sterculiaceae). Phylogenetic relationships within Reevesia suggested that two species, R. pubescens and R. thyrsoidea, as newly defined, are not monophyletic. Six taxa, R. membranacea, R. xuefengensis, R. botingensis, R. lofouensis, R. longipetiolata and R. pycnantha, are suggested to be recognized.

Global One Health index for zoonoses: A performance assessment in 160 countries and territories.

The One Health (OH) approach is used to control/prevent zoonotic events. However, there is a lack of tools for systematically assessing OH practices. Here, we applied the Global OH Index (GOHI) to evaluate the global OH performance for zoonoses (GOHI-Zoonoses). The fuzzy analytic hierarchy process algorithm and fuzzy comparison matrix were used to calculate the weights and scores of five key indicators, 16 subindicators, and 31 datasets for 160 countries and territories worldwide. The distribution of GOHI-Zoonoses scores varies significantly across countries and regions, reflecting the strengths and weaknesses in controlling or responding to zoonotic threats. Correlation analyses revealed that the GOHI-Zoonoses score was associated with economic, sociodemographic, environmental, climatic, and zoological factors. Additionally, the Human Development Index had a positive effect on the score. This study provides an evidence-based reference and guidance for global, regional, and country-level efforts to optimize the health of people, animals, and the environment.

Identification and coregulation pattern analysis of long noncoding RNAs in the mouse brain after Angiostrongylus cantonensis infection.

BACKGROUND: Angiostrongyliasis is a highly dangerous infectious disease. Angiostrongylus cantonensis larvae migrate to the mouse brain and cause symptoms, such as brain swelling and bleeding. Noncoding RNAs (ncRNAs) are novel targets for the control of parasitic infections. However, the role of these molecules in A. cantonensis infection has not been fully clarified. METHODS: In total, 32 BALB/c mice were randomly divided into four groups, and the infection groups were inoculated with 40 A. cantonensis larvae by gavage. Hematoxylin and eosin (H&E) staining and RNA library construction were performed on brain tissues from infected mice. Differential expression of long noncoding RNAs (lncRNAs) and mRNAs in brain tissues was identified by high-throughput sequencing. The pathways and functions of the differentially expressed lncRNAs were determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. The functions of the differentially expressed lncRNAs were further characterized by lncRNA‒microRNA (miRNA) target interactions. The potential host lncRNAs involved in larval infection of the brain were validated by quantitative real-time polymerase chain reaction (qRT‒PCR). RESULTS: The pathological results showed that the degree of brain tissue damage increased with the duration of infection. The transcriptome results showed that 859 lncRNAs and 1895 mRNAs were differentially expressed compared with those in the control group, and several lncRNAs were highly expressed in the middle-late stages of mouse infection. GO and KEGG pathway analyses revealed that the differentially expressed target genes were enriched mainly in immune system processes and inflammatory response, among others, and several potential regulatory networks were constructed. CONCLUSIONS: This study revealed the expression profiles of lncRNAs in the brains of mice after infection with A. cantonensis. The lncRNAs H19, F630028O10Rik, Lockd, AI662270, AU020206, and Mexis were shown to play important roles in the infection of mice with A. cantonensis infection.

The Potential Role of Virus Infection in the Progression of Thyroid Cancer.

Multiple factors have engaged in the progression of thyroid cancer (TC). Recent studies have shown that viral infection can be a critical factor in the pathogenesis of TC. Viruses, such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may play an essential role in the occurrence, development, and even prognosis in TC. This review mainly explored the potential role of viral infection in the progress of TC. The possible mechanisms could be recognizing the host cell, binding to the receptors, affecting oncogenes levels, releasing viral products to shape a beneficial environment, interacting with immune cells to induce immune evasion, and altering the pituitary-thyroid axis. Thus, comprehensive knowledge may provide insights into finding molecular targets for diagnosing and treating virus-related TC.

Bortezomib in previously treated phosphatase and tension homology-deficient patients with advanced intrahepatic cholangiocarcinoma: An open-label, prospective and single-centre phase II trial.

INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC) is characterized by a dismal prognosis with limited therapeutic alternatives. To explore phosphatase and tension homolog (PTEN) as a biomarker for proteasome inhibition in ICC, we conducted a phase II trial to assess the second-line efficacy of bortezomib in PTEN-deficient advanced ICC patients. METHODS: A total of 130 patients with advanced ICC in our centre were screened by PTEN immunohistochemical staining between 1 July 2017, and 31 December 2021, and 16 patients were ultimately enrolled and treated with single-agent bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21-day cycle. The primary endpoint was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors v1.1. RESULTS: The median follow-up was 6.55 months (95% confidence interval [CI]: 0.7-19.9 months). Among the 16 enrolled patients, the ORR was 18.75% (3/16) and the disease control rate was 43.75% (7/16). The median progress-free survival was 2.95 months (95% CI: 2.1-5.1 months) and the median overall survival (mOS) was 7.2 months (95% CI: 0.7-21.6 months) in the intent-to-treat-patients. Treatment-related adverse events of any grade were reported in 16 patients, with thrombopenia being the most common toxicity. Patients with PTEN staining scores of 0 were more likely to benefit from bortezomib than those with staining scores > 0. CONCLUSIONS: Bortezomib yielded an encouraging objective response and a favourable OS as a second-line agent in PTEN-deficient ICC patients. Our findings suggest bortezomib as a promising therapeutic option for patients with PTEN-deficient ICC. HIGHLIGHTS: There is a limited strategy for the second-line option of intrahepatic cholangiocarcinoma (ICC). This investigator-initiated phase 2 study evaluated bortezomib in ICC patients with phosphatase and tension homology deficiency. The overall response rate was 18.75% and the overall survival was 7.2 months in the intent-to-treat cohort. These results justify further developing bortezomib in ICC patients with PTEN deficiency.

Gradient Variation and Correlation Analysis of Physical and Mechanical Properties of Moso Bamboo (Phyllostachys edulis).

This study aimed to investigate the gradient properties of bamboo at the microscopic level and provide a basis for improving the utilization rate of bamboo. Using moso bamboo (Phyllostachys edulis (Carrière) J. Houz.) as a research subject, the variation of vascular bundle area percentage, chemical content, relative crystallinity (CR), mechanical properties of different bamboo slivers, and correlation between those parameters were analyzed. From the bamboo green layer (BGL) to the bamboo yellow layer (BYL), the distribution of vascular bundles changed from dense to sparse. Cellulose and lignin mass content decreased gently, and hemicellulose mass content showed gradual increases. The CR showed an order of bamboo middle layer (BML) > BGL > BYL. The tensile modulus of elasticity, tensile strength, bending modulus of elasticity, and bending strength decreased from BGL to BYL. The order of influence degree on mechanical properties of moso bamboo was vascular bundle area, hemicellulose content, lignin mass content, density, and CR, and these factors correlated with mechanical properties at a significant level (p < 0.05). Vascular bundle area had a decisive effect on the mechanical properties of bamboo. The vascular bundle area and density were linearly correlated with mechanical properties, while the lignin mass content and CR were curve-linearly correlated with mechanical properties.

Expression of genes related to gonadal development and construction of gonadal DNA methylation maps of Trachinotus blochii under hypoxia.

Chronic hypoxia can affect the growth and metabolism of fish and potentially impact gonadal development through epigenetic regulation. Trachinotus blochii (Golden pompano) is widely cultured near the coast and is sensitive to low oxygen conditions. We found that hypoxia and reoxygenation processes acted on multiple targets on the HPG axis, leading to endocrine disorders. Changes in the expression of key genes in the brain (gnrh), pituitary (fsh and lh), ovaries (cyp19a1a, foxl2, and er), and testes (dmrt1, ar, sox9, and gsdf) were associated with significant decreases in estrogen and testosterone levels. Hypoxia and reoxygenation lead to changes in DNA methylation levels in the gonads. Hypoxia upregulated the expression of dnmt1, dnmt3a, dnmt3b, tet1, and tet2 in females and dnmt3a and dnmt3b in males, while reoxygenation down-regulated the expression of dnmt1, dnmt3a, dnmt3b, tet1, and tet2 in males. Whole genome methylation sequencing showed that the number of differentially methylated regions was highest on chromosome 10 (5192) and lowest on chromosome 24 (275). Differentially methylated genes in females and males, as well as between males and females, were enriched in the oxytocin signaling pathway, fatty acid metabolism pathway, and HIF-1a pathway. In summary, hypoxia and reoxygenation can induce endocrine disorders, affect the expression of HPG axis genes, change the methylation pattern and modification pattern of gonad DNA, and then have potential effects on gonad development.