A Mechanistic Analysis of Metformin's Biphasic Effects on Lifespan and Healthspan in C. elegans: Elixir in Youth, Poison in Elder.

Aging, a complex biological process influenced by genetic, environmental, and pharmacological factors, presents a significant challenge in understanding its underlying mechanisms. In this study, we explored the divergent impacts of metformin treatment on the lifespan and healthspan of young and old C. elegans, demonstrating a intriguing "elixir in youth, poison in elder" phenomenon. By scrutinizing the gene expression changes in response to metformin in young (day 1 of adulthood) and old (days 8) groups, we identified nhr-57 and C46G7.1 as potential modulators of age-specific responses. Notably, nhr-57 and C46G7.1 exhibit contrasting regulation patterns, being up-regulated in young worms but down-regulated in old counterparts following metformin treatment. Functional studies employing knockdown approaches targeting nhr-57, a gene under the control of hif-1 with a documented protective function against pore-forming toxins in C. elegans, and C46G7.1, unveiled their critical roles in modulating lifespan and healthspan, as well as in mediating the biphasic effects of metformin. Furthermore, deletion of hif-1 retarded the influence of metformin, implicating the involvement of hif-1/nhr-57 in age-specific drug responses. These findings underscored the necessity of deciphering the mechanisms governing age-related susceptibility to pharmacological agents to tailor interventions for promoting successful aging.

Is Type 2 Diabetes Mellitus Associated with Spinal Degenerative Disorders?: Evidence from Observational and 2-Sample Mendelian Randomization Analyses.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and spinal degenerative disorders (SDD) are common diseases that frequently coexist. However, both traditional observational studies and recent Mendelian randomization (MR) studies have demonstrated conflicting evidence on the association between T2DM and SDD. This comparative study explored and compared the association between T2DM and SDD using observational and MR analyses. METHODS: For observational analyses, cross-sectional studies (44,972 participants with T2DM and 403,095 participants without T2DM), case-control studies (38,234 participants with SDD and 409,833 participants without SDD), and prospective studies (35,550 participants with T2DM and 392,046 participants without T2DM with follow-up information until 2022) were performed to test the relationship between T2DM and SDD using individual-level data from the U.K. Biobank from 2006 to 2022. For MR analyses, the associations between single-nucleotide polymorphisms with SDD susceptibility obtained using participant data from the U.K. Biobank, which had 407,938 participants from 2006 to 2022, and the FinnGen Consortium, which had 227,388 participants from 2017 to 2022, and genetic predisposition to T2DM obtained using summary statistics from a pooled genome-wide association study involving 1,407,282 individuals were examined. The onset and severity of T2DM are not available in the databases being used. RESULTS: Participants with T2DM were more likely to have SDD than their counterparts. Logistic regression analysis identified T2DM as an independent risk factor for SDD, which was confirmed by the Cox proportional hazard model results. However, using single-nucleotide polymorphisms as instruments, the MR analyses demonstrated no causal relationship between T2DM and SDD. The lack of such an association was robust in the sensitivity analysis, and no pleiotropy was seen. CONCLUSIONS: Our results suggest that the association between T2DM and SDD may be method-dependent. Researchers and clinicians should be cautious in interpreting the association, especially the causal association, between T2DM and SDD. Our findings provide fresh insights into the association between T2DM and SDD by various analysis methods and guide future research and clinical efforts in the effective prevention and management of T2DM and SDD. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Ruthenium Complexes with NNN-Pincer Ligands for N-Methylation of Amines Using Methanol.

A series of ruthenium complexes (Ru1-Ru4) bearing new NNN-pincer ligands were synthesized in 58-78% yields. All of the complexes are air and moisture stable and were characterized by IR, NMR, and high-resolution mass spectra (HRMS). In addition, the structures of Ru1-Ru3 were confirmed by X-ray crystallographic analysis. These Ru(II) complexes exhibited high catalytic efficiency and broad functional group tolerance in the N-methylation reaction of amines using CH3OH as both the C1 source and solvent. Experimental results indicated that the electronic effect of the substituents on the ligands considerably affects the catalytic reactivity of the complexes in which Ru3 bearing an electron-donating OMe group showed the highest activity. Deuterium labeling and control experiments suggested that the dehydrogenation of methanol to generate ruthenium hydride species was the rate-determining step in the reaction. Furthermore, this protocol also provided a ready approach to versatile trideuterated N-methylamines under mild conditions using CD3OD as a deuterated methylating agent.

Sodium thiosulfate: A donor or carrier signaling molecule for hydrogen sulfide?

Sodium thiosulfate has been used for decades in the treatment of calciphylaxis and cyanide detoxification, and has recently shown initial therapeutic promise in critical diseases such as neuronal ischemia, diabetes mellitus, heart failure and acute lung injury. However, the precise mechanism of sodium thiosulfate remains incompletely defined and sometimes contradictory. Although sodium thiosulfate has been widely accepted as a donor of hydrogen sulfide (H2S), emerging findings suggest that it is the executive signaling molecule for H2S and that its effects may not be dependent on H2S. This article presents an overview of the current understanding of sodium thiosulfate, including its synthesis, biological characteristics, and clinical applications of sodium thiosulfate, as well as the underlying mechanisms in vivo. We also discussed the interplay of sodium thiosulfate and H2S. Our review highlights sodium thiosulfate as a key player in sulfide signaling with the broad clinical potential for the future.

Differential impacts of nonsteroidal anti-inflammatory drugs on lifespan and healthspan in aged Caenorhabditis elegans.

Aging and age-related diseases are intricately associated with oxidative stress and inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown their promise in mitigating age-related conditions and potentially extending lifespan in various model organisms. However, the efficacy of NSAIDs in older individuals may be influenced by age-related changes in drug metabolism and tolerance, which could result in age-dependent toxicities. This study aimed to evaluate the potential risks of toxicities associated with commonly used NSAIDs (aspirin, ibuprofen, acetaminophen, and indomethacin) on lifespan, healthspan, and oxidative stress levels in both young and old Caenorhabditis elegans. The results revealed that aspirin and ibuprofen were able to extend lifespan in both young and old worms by suppressing ROS generation and enhancing the expression of antioxidant SOD genes. In contrast, acetaminophen and indomeacin accelerated aging process in old worms, leading to oxidative stress damage and reduced resistance to heat stress through the pmk-1/skn-1 pathway. Notably, the harmful effects of acetaminophen and indomeacin were mitigated when pmk-1 was knocked out in the pmk-1(km25) strain. These results underscore the potential lack of benefit from acetaminophen and indomeacin in elderly individuals due to their increased susceptibility to toxicity. Further research is essential to elucidate the underlying mechanisms driving these age-dependent responses and to evaluate the potential risks associated with NSAID use in the elderly population.

Selective hydrodeoxygenation of lignin-derived phenolic monomers to cyclohexanol over tungstated zirconia supported ruthenium catalysts.

The selective hydrodeoxygenation (HDO) of lignin-derived methoxyphenols to cyclohexanol is one of the most significant transformation in biomass conversion since cyclohexanol is an important industrial raw material. This study has disclosed a series of tungstated zirconia with different Zr/W ratio supported Ru catalysts (Ru/xZrW, x means the molar ration of Zr/W) for the hydrodeoxygenation (HDO) of guaiacol to cyclohexanol. Among these catalysts, Ru/16ZrW has the best catalytic activity, which can achieve 92% yield of cyclohexanol under the conditions of 180 oC and 1 MPa H2 pressure for 2 h (TOF 231 h-1). Compared with Ru/ZrO2, Ru/16ZrW has smaller particles, more dispersed and electron-rich Ru species, significant hydrogen spillover and more acid sites, which are the main reason for its excellent performance on this reaction. Apart from guaiacol, other methoxy substitution phenols and organosolv lignin can also be converted into cyclohexanol via hydrodeoxygenation reactions over this catalyst.

Technical variety of anastomotic techniques used in proximal gastrectomy with double-tract-reconstruction - a narrative review.

In the past 40 years, the incidence of esophagogastric junction cancer has been gradually increasing worldwide. Currently, surgical resection remains the main radical treatment for early gastric cancer. Due to the rise of functional preservation surgery, proximal gastrectomy has become an alternative to total gastrectomy for surgeons in Japan and South Korea. However, the methods of digestive tract reconstruction after proximal gastrectomy have not been fully unified. At present, the principal methods include esophagogastrostomy, double flap technique, jejunal interposition, and double tract reconstruction. Related studies have shown that double tract reconstruction has a good anti-reflux effect and improves postoperative nutritional prognosis, and it is expected to become a standard digestive tract reconstruction method after proximal gastrectomy. However, the optimal anastomoses mode in current double tract reconstruction is still controversial. This article aims to review the current status of double tract reconstruction and address the aforementioned issues.

[Percutaneous pedicle screw anchored vertebral augmentation for the treatment of Kümmell disease without neurological symptoms].

OBJECTIVE: To explore the clinical effect of percutaneous pedicle screw anchored vertebral augmentation(PPSAVA) in the treatment of asymptomatic Kümmell disease without neurological symptoms. METHODS: The clinical data of 20 patients with Kümmell disease without neurological symptoms treated with PPSAVA in our hospital from January 2019 to December 2021 were analyzed retrospectively, including 5 males and 15 females, aged 56 to 88 (74.95±9.93) years old. and the course of disease was 7 to 60 days with an average of (21.35±14.46) days. All patients were treated with PPSAVA. The time of operation, the amount of bone cement injected and the leakage of bone cement were recorded. The visual analogue scale(VAS), Oswestry disability index(ODI), vertebral body angle(VBA), anterior edge height and midline height of vertebral body were compared among the before operation, 3 days after operation and during the final follow-up. The loosening and displacement of bone cement were observed during the final follow-up. RESULTS: All the 20 patients completed the operation successfully. The operation time was 30 to 56 min with an average of (41.15±7.65) min, and the amount of bone cement injection was 6.0 to 12.0 ml with an average of (9.30±1.49) ml. Bone cement leakage occurred in 6 cases and there were no obvious clinical symptoms. The follow-up time was 6 to 12 months with an average of (8.43±2.82) months. The VBA, anterior edge height and midline height of of injured vertebral body were significantly improved 3 days after operation and the final follow-up(P<0.05), and the VBA, anterior edge height and midline height of of injured vertebral body were lost in different degrees at the final follow-up (P<0.05). The VAS and ODI at 3 days after operation and at the final follow-up were significantly lower than those at preoperatively(P<0.05), but the VAS score and ODI at the final follow-up were not significantly different from those at 3 d after operation(P>0.05). At the last follow-up, no patients showed loosening or displacement of bone cement. CONCLUSION: PPSAVA is highly effective in treating Kümmell disease without neurological symptoms, improving patients' pain and functional impairment, and reducing the risk of cement loosening and displacement postoperatively.

Hypoxaemia risk in pediatric flexible bronchoscopy for foreign body removal: a retrospective study.

BACKGROUND: Hypoxemia represents the most prevalent adverse event during flexible bronchoscopy procedures aimed at foreign body retrieval in pediatric patients; if not expeditiously managed, it carries the potential for cardiac or respiratory arrest. The specific risk factors contributing to the occurrence of hypoxemia during foreign body FB removal via bronchoscopy have yet to be definitively established. METHODS: This retrospective study included a cohort of 266 pediatric subjects from January 1, 2015, to December 31, 2022, who underwent flexible bronchoscopy for the purpose of FB extraction. In this cohort, the supraglottic airway was used to connect the anesthesia apparatus during the removal procedure. RESULTS: In total, 45 of the pediatric patients (16.9%) experienced episodes of hypoxemia during the FB removal procedure. Multivariate analysis revealed that the following factors were significantly associated with the occurrence of hypoxemia: an operation time exceeding 60 min (odds ratio [OR] 8.55; 95% confidence interval [CI] 3.82-19.13), a maximum diameter exceeding 7 mm (OR 5.03; 95% CI, 2.24-11.29), and the presence of radiological evidence indicating pneumonia (OR 2.69; 95% CI, 1.27-5.69). CONCLUSION: During flexible bronchoscopy procedures aimed at FB removal in pediatric patients, there is an increased susceptibility to hypoxemia. Factors including extended operation duration, larger FB dimensions, and radiographic evidence suggestive of pneumonia significantly contribute to a heightened risk of hypoxemia.

Impact of Gender-Role Attitudes and Mental Health on Hostile Sexism and Acceptance of Cosmetic Surgery.

BACKGROUND: Each year, tens of thousands of people worldwide choose to undergo cosmetic surgery in order to alter their appearance. In recent years, young people have gradually emerged to comprise the main driving force behind the increasing demand for cosmetic surgery. Previous studies have found that sexism may motivate young people to undergo such surgeries. However, few studies have been conducted to determine if this psychological mechanism influences the acceptance of cosmetic surgery among Chinese university students. METHODS: A total of 579 Chinese university students (280 girls and 299 boys, 17-20 years) volunteered to participate in the online survey. They completed a questionnaire containing the Ambivalent Sexism Inventory, the 12-item General Health Questionnaire, the Gender-Role Attitudes Questionnaire and the Acceptance of Cosmetic Surgery Scale. We firstly evaluated the underlying factor structure of the Acceptance of Cosmetic Surgery Scale using exploratory and confirmatory factor analyses, and exploring pattern of associations between the constructs was analyzed via path analysis. RESULTS: According to the findings, hostile sexism was associated with greater levels of acceptance toward cosmetic surgery. Moreover, gender-role attitudes mediated the link between hostile sexism and the acceptance of cosmetic surgery, and this mediation was positively influenced by general mental health. CONCLUSION: Our study contributes to a deeper understanding of Chinese university students' attitudes toward cosmetic surgery, hostile sexism may contribute to normalizing traditional gender stereotypes and encourage cosmetic surgery acceptability among Chinese university students. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effects of returning paddy field to wetland on composition and stability of soil aggregates in the Yellow River Delta.

The composition and stability of soil aggregates are important indicators for measuring soil quality, which would be affected by land use changes. Taking wetlands with different returning years (2 and 15 years) in the Yellow River Delta as the research object, paddy fields and natural wetlands as control, we analyzed the changes in soil physicochemical properties and soil aggregate composition. The results showed that soil water content, total organic carbon, dissolved organic carbon and total phosphorus of the returning soil (0-40 cm) showed an overall increasing trend with returning period, while soil pH and bulk density was in adverse. There was no significant change in clay content, electrical conductivity, and total nitrogen content. The contents of macro-aggregates and micro-aggregates showed overall increasing and decreasing trend with returning period, respectively. The stability of aggregates in the topsoil (0-10 cm) increased with returning years. Geometric mean diameter and mean weight diameter increased by 8.9% and 40.4% in the 15th year of returning, respectively, while the mass proportion of >2.5 mm fraction decreased by 10.5%. There was no effect of returning on aggregates in subsoil (10-40 cm). Our results indicated that returning paddy field to wetland in the Yellow River Delta would play a positive role in improving soil structure and aggregate stability.

Targeting EFHD2 inhibits interferon-γ signaling and ameliorates non-alcoholic steatohepatitis.

BACKGROUND & AIMS: The precise pathomechanisms underlying the development of non-alcoholic steatohepatitis (NASH, also known as metabolic dysfunction-associated steatohepatitis [MASH]) remain incompletely understood. In this study, we investigated the potential role of EF-hand domain family member D2 (EFHD2), a novel molecule specific to immune cells, in the pathogenesis of NASH. METHODS: Hepatic EFHD2 expression was characterized in patients with NASH and two diet-induced NASH mouse models. Single-cell RNA sequencing (scRNA-seq) and double-immunohistochemistry were employed to explore EFHD2 expression patterns in NASH livers. The effects of global and myeloid-specific EFHD2 deletion on NASH and NASH-related hepatocellular carcinoma were assessed. Molecular mechanisms underlying EFHD2 function were investigated, while chemical and genetic investigations were performed to assess its potential as a therapeutic target. RESULTS: EFHD2 expression was significantly elevated in hepatic macrophages/monocytes in both patients with NASH and mice. Deletion of EFHD2, either globally or specifically in myeloid cells, improved hepatic steatosis, reduced immune cell infiltration, inhibited lipid peroxidation-induced ferroptosis, and attenuated fibrosis in NASH. Additionally, it hindered the development of NASH-related hepatocellular carcinoma. Specifically, deletion of myeloid EFHD2 prevented the replacement of TIM4+ resident Kupffer cells by infiltrated monocytes and reversed the decreases in patrolling monocytes and CD4+/CD8+ T cell ratio in NASH. Mechanistically, our investigation revealed that EFHD2 in myeloid cells interacts with cytosolic YWHAZ (14-3-3ζ), facilitating the translocation of IFNγR2 (interferon-γ receptor-2) onto the plasma membrane. This interaction mediates interferon-γ signaling, which triggers immune and inflammatory responses in macrophages during NASH. Finally, a novel stapled α-helical peptide targeting EFHD2 was shown to be effective in protecting against NASH pathology in mice. CONCLUSION: Our study reveals a pivotal immunomodulatory and inflammatory role of EFHD2 in NASH, underscoring EFHD2 as a promising druggable target for NASH treatment. IMPACT AND IMPLICATIONS: Non-alcoholic steatohepatitis (NASH) represents an advanced stage of non-alcoholic fatty liver disease (NAFLD); however, not all patients with NAFLD progress to NASH. A key challenge is identifying the factors that trigger inflammation, which propels the transition from simple fatty liver to NASH. Our research pinpointed EFHD2 as a pivotal driver of NASH, orchestrating the over-activation of interferon-γ signaling within the liver during NASH progression. A stapled peptide designed to target EFHD2 exhibited therapeutic promise in NASH mice. These findings support the potential of EFHD2 as a therapeutic target in NASH.

Exploring the Correlation between Azido-Tetrazolo Tautomerizations and Isomer Structures: Electron Density of Bonding N Atoms and N-N Bond Polarity.

Azido-tetrazolo tautomerizations between azido N-heteroaromatic compounds and tetrazole-fused energetic materials can produce a new generation of high-energy density compounds. Density functional theory (DFT) computations are performed to explore the relationship between reaction barriers and electron densities of bonding N atoms, i.e., the terminal N1 and heterocyclic N2 atoms, for six reported tautomerizations. The results reveal four linear correlations between reverse reaction barriers (Gr) and the electron densities of N1 and N2 atoms in the product. N1 electron density (ρN1) and N-N bond polarity, as measured by the difference between the electron densities on the two N atoms (ΔρN = ρN1 - ρN2) in products, are inversely proportional to the reverse reaction barriers. They are also proportional to the energy barrier differences between the forward and reverse reactions (ΔG = Gf - Gr). Polar solvents, including DMSO, water, and acetone, can effectively increase the reverse reaction barriers (Gr) by improving the stability of products. This regularity is further confirmed by its application to four additional tautomerizations and can be used to screen out unfavorable azido-tetrazolo tautomerization reactions and increase the success rate of such synthesis.

Multifunctional Polyoxometalates-Based Ionohydrogels toward Flexible Electronics.

Multifunctional flexible electronics present tremendous opportunities in the rapidly evolving digital age. One potential avenue to realize this goal is the integration of polyoxometalates (POMs) and ionic liquid-based gels (ILGs), but the challenge of macrophase separation due to poor compatibility, especially caused by repulsion between like-charged units, poses a significant hurdle. Herein, the possibilities of producing diverse and homogenous POMs-containing ionohydrogels by nanoconfining POMs and ionic liquids (ILs) within an elastomer-like polyzwitterionic hydrogel using a simple one-step random copolymerization method, are expanded vastly. The incorporation of polyzwitterions provides a nanoconfined microenvironment and effectively modulates excessive electrostatic interactions in POMs/ILs/H2O blending system, facilitating a phase transition from macrophase separation to a submillimeter scale worm-like microphase-separation system. Moreover, combining POMs-reinforced ionohydrogels with a developed integrated self-powered sensing system utilizing strain sensors and Zn-ion hybrid supercapacitors has enabled efficient energy storage and detection of external strain changes with high precision. This work not only provides guidelines for manipulating morphology within phase-separation gelation systems, but also paves the way for developing versatile POMs-based ionohydrogels for state-of-the-art smart flexible electronics.

S-Doping Regulated Iron Spin States in Fe-N-C Single-Atom Material for Enhanced Peroxidase-Mimicking Activity at Neutral pH.

Designing biomimetic nanomaterials with peroxidase (POD)-like activity at neutral pH remains a significant challenge. An S-doping strategy is developed to afford an iron single-atom nanomaterial (Fe1@CN-S) with high POD-like activity under neutral conditions. To the best of knowledge, there is the first example on the achievement of excellent POD-like activity under neutral conditions by regulating the active site structure. S-doping not only promotes the dissociation of the N─H bond in 3,3″,5,5″-tetramethylbenzidine (TMB), but also facilitates the desorption of OH* by the transformation of iron species' spin states from middle-spin (MS FeII) to low-spin (LS FeII). Meanwhile, LS FeII sites typically have more unfilled d orbitals, thereby exhibiting stronger interactions with H2O2 than MS FeII, which can enhance POD-like activity. Finally, a one-pot visual detection of glucose at pH 7 is performed, demonstrating the best selectivity and sensitivity than previous reports.

Nanozyme sensor array based on Fe, Se co-doped carbon material for the discrimination of Sulfur-containing compounds.

Developing methods for the accurate identification and analysis of sulfur-containing compounds (SCCs) is of great significance because of their essential roles in living organisms and the diagnosis of diseases. Herein, Se-doping improved oxidase-like activity of iron-based carbon material (Fe-Se/NC) was prepared and applied to construct a four-channel colorimetric sensor array for the detection and identification of SCCs (including biothiols and sulfur-containing metal salts). Fe-Se/NC can realize the chromogenic oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by activating O2 without relying on H2O2, which can be inhibited by different SCCs to diverse degrees to produce different colorimetric response changes as "fingerprints" on the sensor array. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) revealed that nine kinds of SCCs could be well discriminated. The sensor array was also applied for the detection of SCCs with a linear range of 1-50 µM and a limit of detection of 0.07-0.2 µM. Moreover, colorimetric sensor array inspired by the different levels of SCCs in real samples were used to discriminate cancer cells and food samples, demonstrating its potential application in the field of disease diagnosis and food monitoring. ENVIRONMENTAL IMPLICATIONS: In this work, a four-channel colorimetric sensor array for accurate SCCs identification and detection was successfully constructed. The colorimetric sensor array inspired by the different levels of SCCs in real samples were also used to discriminate cancer cells and food samples. Therefore, this Fe-Se/NC based sensor array is expected to be applied in the field of environmental monitoring and environment related disease diagnosis.

Pharmacological approaches for targeting lysosomes to induce ferroptotic cell death in cancer.

Lysosomes are crucial organelles responsible for the degradation of cytosolic materials and bulky organelles, thereby facilitating nutrient recycling and cell survival. However, lysosome also acts as an executioner of cell death, including ferroptosis, a distinctive form of regulated cell death that hinges on iron-dependent phospholipid peroxidation. The initiation of ferroptosis necessitates three key components: substrates (membrane phospholipids enriched with polyunsaturated fatty acids), triggers (redox-active irons), and compromised defence mechanisms (GPX4-dependent and -independent antioxidant systems). Notably, iron assumes a pivotal role in ferroptotic cell death, particularly in the context of cancer, where iron and oncogenic signaling pathways reciprocally reinforce each other. Given the lysosomes' central role in iron metabolism, various strategies have been devised to harness lysosome-mediated iron metabolism to induce ferroptosis. These include the re-mobilization of iron from intracellular storage sites such as ferritin complex and mitochondria through ferritinophagy and mitophagy, respectively. Additionally, transcriptional regulation of lysosomal and autophagy genes by TFEB enhances lysosomal function. Moreover, the induction of lysosomal iron overload can lead to lysosomal membrane permeabilization and subsequent cell death. Extensive screening and individually studies have explored pharmacological interventions using clinically available drugs and phytochemical agents. Furthermore, a drug delivery system involving ferritin-coated nanoparticles has been specifically tailored to target cancer cells overexpressing TFRC. With the rapid advancements in understandings the mechanistic underpinnings of ferroptosis and iron metabolism, it is increasingly evident that lysosomes represent a promising target for inducing ferroptosis and combating cancer.

Hierarchical blind phase search for correcting imperfect phase rotation in QAM signals synthesized via optical coherent superposition.

Coherent superposition has been proposed to synthesize high-order quadrature amplitude modulation (QAM) by coherently superposing low-order QAMs in the optical domain. These approaches could effectively relax the digital-to-analog converter resolution and reduce the complexity of the driving electronics. However, in the superposition process, imperfect phase rotations (IPRs) in low-order QAMs will be transferred to the resultant high-order QAM. Importantly, the induced IPR cannot be compensated for by conventional linear equalizers and carrier recovery methods. To combat the induced IPR, herein, we propose a hierarchical blind phase search (HBPS) algorithm to compensate for the IPRs in synthesized high-order QAMs. The proposed HBPS can match the generation mechanism of the IPRs in coherent superposition, by tracing back and estimating the IPR in the QPSK-like constellation of each hierarchy and finally correcting the induced IPRs. Simulation and experimental results verify that this algorithm could effectively compensate for the IPR in the resultant 16-QAMs synthesized using coherent superposition approaches. The proposed HBPS shows significant optical signal-to-noise ratio (OSNR) gains compared to the conventional blind phase search (BPS) method for high-order QAMs coherently superposed using optical signal processing (OSP) and tandem modulators (TMs). Specifically, at the BER of 2.4e-2, the HBPS achieves a 1.5-dB OSNR sensitivity enhancement over the BPS in either OSP or TMs-based schemes, even with an imperfection rotation of up to 20∘.

A Coding Framework and Benchmark Towards Low-Bitrate Video Understanding.

Video compression is indispensable to most video analysis systems. Despite saving the transportation bandwidth, it also deteriorates downstream video understanding tasks, especially at low-bitrate settings. To systematically investigate this problem, we first thoroughly review the previous methods, revealing that three principles, i.e., task-decoupled, label-free, and data-emerged semantic prior, are critical to a machine-friendly coding framework but are not fully satisfied so far. In this paper, we propose a traditional-neural mixed coding framework that simultaneously fulfills all these principles, by taking advantage of both traditional codecs and neural networks (NNs). On one hand, the traditional codecs can efficiently encode the pixel signal of videos but may distort the semantic information. On the other hand, highly non-linear NNs are proficient in condensing video semantics into a compact representation. The framework is optimized by ensuring that a transportation-efficient semantic representation of the video is preserved w.r.t. the coding procedure, which is spontaneously learned from unlabeled data in a self-supervised manner. The videos collaboratively decoded from two streams (codec and NN) are of rich semantics, as well as visually photo-realistic, empirically boosting several mainstream downstream video analysis task performances without any post-adaptation procedure. Furthermore, by introducing the attention mechanism and adaptive modeling scheme, the video semantic modeling ability of our approach is further enhanced. Fianlly, we build a low-bitrate video understanding benchmark with three downstream tasks on eight datasets, demonstrating the notable superiority of our approach. All codes, data, and models will be open-sourced for facilitating future research.

A feedback regulation of FgHtf1-FgCon7 loop in conidiogenesis and development of Fusarium graminearum.

The transcription factor FgHtf1 is important for conidiogenesis in Fusarium graminearum and it positively regulates the expression of the sporulation-related gene FgCON7. However, the regulatory mechanism underlying its functions is still unclear. The present study intends to uncover the functional mechanism of FgHtf1 in relation to FgCon7 in F. graminearum. We demonstrated that FgCON7 serves as a target gene for FgHtf1. Interestingly, FgCon7 also binds the promoter region of FgHTF1 to negatively regulate its expression, thus forming a negative-feedback loop. We demonstrated that FgHtf1 and FgCon7 have functional redundancy in fungal development. FgCon7 localizes in the nucleus and has transcriptional activation activity. Deletion of FgCON7 significantly reduces conidia production. 4444 genes were regulated by FgCon7 in ChIP-Seq, and RNA-Seq revealed 4430 differentially expressed genes in FgCON7 deletion mutant, with CCAAT serving as a consensus binding motif of FgCon7 to the target genes. FgCon7 directly binds the promoter regions of FgMSN2, FgABAA, FgVEA and FgSMT3 genes and regulates their expression. These genes were found to be important for conidiogenesis. To our knowledge, this is the first study that unveiled the mutual regulatory functions of FgCON7 and FgHTF1 to form a negative-feedback loop, and how the loop mediates sporulation in F. graminearum.