Prognostic value of a nomogram model for postoperative liver metastasis of colon cancer.

BACKGROUND: Colon cancer is one of the most common malignant tumors of the digestive system. Liver metastasis after colon cancer surgery is the primary cause of death in patients with colon cancer. AIM: To construct a novel nomogram model including various factors to predict liver metastasis after colon cancer surgery. METHODS: We retrospectively analyzed 242 patients with colon cancer who were admitted and underwent radical resection for colon cancer in Zhejiang Provincial People's Hospital from December 2019 to December 2022. Patients were divided into liver metastasis and non-liver metastasis groups. Sex, age, and other general and clinicopathological data (preoperative blood routine and biochemical test indexes) were compared. The risk factors for liver metastasis were analyzed using single-factor and multifactorial logistic regression. A predictive model was then constructed and evaluated for efficacy. RESULTS: Systemic inflammatory index (SII), C-reactive protein/albumin ratio (CAR), red blood cell distribution width (RDW), alanine aminotransferase, preoperative carcinoembryonic antigen level, and lymphatic metastasis were different between groups (P < 0.05). SII, CAR, and RDW were risk factors for liver metastasis after colon cancer surgery (P < 0.05). The area under the curve was 0.93 for the column-line diagram prediction model constructed based on these risk factors to distinguish whether liver metastasis occurred postoperatively. The actual curve of the column-line diagram predicting the risk of postoperative liver metastasis was close to the ideal curve, with good agreement. The prediction model curves in the decision curve analysis showed higher net benefits for a larger threshold range than those in extreme cases, indicating that the model is safer. CONCLUSION: Liver metastases after colorectal cancer surgery could be well predicted by a nomogram based on the SII, CAR, and RDW.

Discovery of a potent Gilteritinib-based FLT3-PROTAC degrader for the treatment of Acute myeloid leukemia.

Fms-like tyrosine receptor kinase 3 (FLT3) proteolysis targeting chimeras (PROTACs) emerge as a promising approach to overcome the limitations of FLT3 inhibitors, while the development of orally bioavailable FLT3-PROTACs faces great challenges. Here, we report the rational design and evaluation of a series of Gilteritinib-based FLT3-PROTACs. Among them, B3-2 exhibited the strongest antiproliferative activity against FLT3-ITD mutant AML cells, and significantly induced FLT3-ITD protein degradation. Mechanistic investigations demonstrated that B3-2 induced FLT3-ITD degradation in a ubiquitin-proteasome-dependent manner. More importantly, B3-2 exhibited an oral bioavailability of 5.65%, and oral administration of B3-2 showed good antitumor activity in MV-4-11 xenograft models. Furthermore, B3-2 showed strong antiproliferative activity against FLT3 resistant mutations, highlighting its potential in overcoming drug resistance.

Discovery of a Novel Orally Bioavailable FLT3-PROTAC Degrader for Efficient Treatment of Acute Myeloid Leukemia and Overcoming Resistance of FLT3 Inhibitors.

Fms-like tyrosine receptor kinase 3 (FLT3) proteolysis-targeting chimeras (PROTACs) represent a promising approach to eliminate the resistance of FLT3 inhibitors. However, due to the poor druggability of PROTACs, the development of orally bioavailable FLT3-PROTACs faces great challenges. Herein, a novel orally bioavailable FLT3-ITD degrader A20 with excellent pharmacokinetic properties was discovered through reasonable design. A20 selectively inhibited the proliferation of FLT3-ITD mutant acute myeloid leukemia (AML) cells and potently induced FLT3-ITD degradation through the ubiquitin-proteasome system. Notably, oral administration of A20 resulted in complete tumor regression on subcutaneous AML xenograft models. Furthermore, on systemic AML xenograft models, A20 could completely eliminate the CD45+CD33+ human leukemic cells in murine and significantly prolonged the survival time of mice. Most importantly, A20 exerted significantly improved antiproliferative activity against drug-resistant AML cells compared to existing FLT3 inhibitors. These findings suggested that A20 could serve as a promising drug candidate for relapsed or refractory AML.

Aconite aqueous extract inhibits the growth of hepatocellular carcinoma through CCL2-dependent enhancement of natural killer cell infiltration.

OBJECTIVE: Aconite is a traditional Chinese herbal medicine that has been found to inhibit the development of liver cancer; however, its exact molecular mechanisms in this process remain unclear. This study explores how aconite aqueous extract (AAE) inhibits hepatocellular carcinoma (HCC). METHODS: An in vivo mouse model of subcutaneous liver cancer was established. After AAE treatment, immunohistochemistry (IHC) was used to determine the effect of AAE on natural killer (NK) cells. Subsequently, C57BL/6 mice were used to establish the subcutaneous tumor model, and a group of these mice were treated with anti-PK163 antibody to remove NK cells, which was verified by flow cytometry and IHC. The effect of AAE on the proliferation of HCC cells in vitro was determined using cell counting kit-8. The effect of AAE on chemokine production in HCC cells was measured using real-time quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay. The effect of AAE on the migration of NK cells was determined using a transwell assay. Finally, the molecular mechanism was investigated using the Western blotting method. RESULTS: We demonstrated that the ability of AAE to induce overexpression of the cytokine C-C motif chemokine ligand 2 (CCL2) in HCC cells is fundamental to the infiltration of NK cells into the tumor bed. Mechanistically, we found that the upregulation of CCL2 was achieved by the activation of c-Jun N-terminal kinase but not extracellular regulated protein kinase or p38. CONCLUSION: Our findings suggest that AAE can be used as an effective immune adjuvant to enhance antitumor immunity by increasing NK cell infiltration into tumors, which could help to improve the efficacy of HCC treatments. Please cite this article as: Yang KD, Zhang X, Shao MC, Wang LN. Aconite aqueous extract inhibits the growth of hepatocellular carcinoma through CCL2-dependent enhancement of natural killer cell infiltration. J Integr Med. 2023; 21(6): 575-583.

Circular RNA (circ)_0053277 Contributes to Colorectal Cancer Cell Growth, Angiogenesis, Metastasis and Glycolysis.

Circular RNAs (circRNAs) have been found to be abnormally expressed in many cancers, including colorectal cancer (CRC). Circ_0053277 has been found to mediate CRC malignant processes and may be a key regulator for CRC progression. Therefore, its role and potential molecular mechanism in CRC process deserve further investigation. Quantitative real-time PCR was used to detect the expression levels of circ_0053277, microRNA-520 h (miR-520 h) and hexokinase 1 (HK1). Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine assay, flow cytometry, wound healing assay, transwell assay, and tube formation assay were used to detect CRC cell proliferation, apoptosis, migration, invasion, and angiogenesis. The protein levels of apoptosis-related markers and HK1 were detected by western blot. The relationship between circ_0053277 and miR-520 h or miR-520 h and HK1 in CRC cells was verified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Cell glycolysis was assessed by detecting glucose uptake and lactate production. The effect of silenced circ_0053277 on CRC tumor growth was evaluated by xenograft model in vivo. Our study found that circ_0053277 expression was elevated in CRC tissues and cells. Moreover, circ_0053277 knockdown suppressed CRC cell proliferation, angiogenesis, migration and invasion, while promoting apoptosis. In terms of mechanism, circ_0053277 sponged miR-520 h, and HK1 was the target of miR-520 h. Meanwhile, miR-520 h inhibitor reversed the inhibitory effect of circ_0053277 silencing on CRC cell progression, and HK1 overexpression also overturned the suppressive effect of miR-520 h on CRC cell growth, angiogenesis and metastasis. Moreover, circ_0053277 knockdown inhibited the glycolysis of CRC cells by regulating miR-520 h/HK1 pathway. In addition, knockdown of circ_0053277 reduced CRC tumor growth in vivo. Circ_0053277 promoted CRC cell growth, angiogenesis, metastasis and glycolysis by miR-520 h/HK1 pathway, confirming that circ_0053277 might be a potential clinical target for CRC treatment.

Exploring Plant Meiosis: Insights from the Kinetochore Perspective.

The central player for chromosome segregation in both mitosis and meiosis is the macromolecular kinetochore structure, which is assembled by >100 structural and regulatory proteins on centromere DNA. Kinetochores play a crucial role in cell division by connecting chromosomal DNA and microtubule polymers. This connection helps in the proper segregation and alignment of chromosomes. Additionally, kinetochores can act as a signaling hub, regulating the start of anaphase through the spindle assembly checkpoint, and controlling the movement of chromosomes during anaphase. However, the role of various kinetochore proteins in plant meiosis has only been recently elucidated, and these proteins differ in their functionality from those found in animals. In this review, our current knowledge of the functioning of plant kinetochore proteins in meiosis will be summarized. In addition, the functional similarities and differences of core kinetochore proteins in meiosis between plants and other species are discussed, and the potential applications of manipulating certain kinetochore genes in meiosis for breeding purposes are explored.

A 37-Year-Old Man with Myofibroblast Sarcoma Combined with Pleural Maculopathy: Case Report.

Myofibroblastic sarcoma (MS) is a malignant tumor of soft tissue or bone that can occur in children or adults, with a high rate of recurrence and metastasis. We report a case of low-grade malignant MS of the left shoulder, diagnosed based on pathological examination and immunohistochemical staining. However, the patient had unexplained pleural maculopathy. The patient passed away 6 months after the diagnosis of myofibroblast sarcoma due to multiple metastases throughout the sarcoma. Combined with the patient's history, ancillary findings, and after MDT discussion, the patient was ultimately considered to have a high probability of myofibroblast sarcoma combined with pleural maculopathy. In conclusion, when a patient is diagnosed with myofibroblast sarcoma in combination with pleural macula, in the absence of other causative factors, a deep tissue biopsy of the pleura should be actively performed to confirm the diagnosis.

Human Disturbance Increases Health Risks to Golden Snub-Nosed Monkeys and the Transfer Risk of Pathogenic Antibiotic-Resistant Bacteria from Golden Snub-Nosed Monkeys to Humans.

From the perspective of interactions in the human-animal-ecosystem, the study and control of pathogenic bacteria that can cause disease in animals and humans is the core content of "One Health". In order to test the effect of human disturbance (HD) on the health risk of pathogenic antibiotic-resistant bacteria (PARBs) to wild animals and transfer risk of the PARBs from wild animals to humans, golden snub-nosed monkeys (Rhinopithecus roxellana) were used as sentinel animals. Metagenomic analysis was used to analyze the characteristics of PARBs in the gut microbiota of golden snub-nosed monkeys. Then, the total contribution of antibiotic resistance genes (ARGs) and virulence factors (VFs) of the PARBs were used to assess the health risk of PARBs to golden snub-nosed monkeys, and the antimicrobial drug resistance and bacterial infectious disease of PARBs were determined to assess the transfer risk of PARBs from golden snub-nosed monkeys to humans. There were 18 and 5 kinds of PARBs in the gut microbiota of golden snub-nosed monkeys under HD (HD group) and wild habitat environments (W group), respectively. The total health risks of PARBs to the W group and the HD group were -28.5 × 10-3 and 125.8 × 10-3, respectively. There were 12 and 16 kinds of KEGG pathways of human diseases in the PARBs of the W group and the HD group, respectively, and the gene numbers of KEGG pathways in the HD group were higher than those in the W group. HD increased the pathogenicity of PARBs to golden snub-nosed monkeys, and the PARBs in golden snub-nosed monkeys exhibited resistance to lincosamide, aminoglycoside, and streptogramin antibiotics. If these PARBs transfer from golden snub-nosed monkeys to humans, then humans may acquire symptoms of pathogens including Tubercle bacillus, Staphylococcus, Streptococcus, Yersinia, Pertussis, and Vibrio cholera.

High-Efficiency Mono-Cyclopentadienyl Titanium and Rare-Earth Metal Catalysts for the Production of Syndiotactic Polystyrene.

Syndiotactic polystyrene (SPS) refers to a type of thermoplastic material with phenyl substituents that are alternately chirally attached on both sides of an aliphatic macromolecular main chain. Owing to its excellent physical and mechanical properties, as well as its chemical stability, high transparency, and electrical insulation characteristics, SPS is used in a wide variety of technical fields. SPS is commonly produced via the stereoselective transition metal-catalyzed coordination polymerization method mediated by stereospecific catalysts, which consists of anionic mono-cyclopentadienyl derivative η5-coordinated single active metal centers (referred to as "mono-Cp'-M"), with active center metals involving Group 4 transition metals (with an emphasis on titanium) and rare-earth (RE) metals of the periodic table. In this context, the use of mono-cyclopentadienyl titanocene (mono-Cp'Ti) catalysts and mono-cyclopentadienyl rare-earth metal (mono-Cp'RE) metallocene catalysts for the syndiospecific polymerization of styrene is discussed. The effects of the mono-cyclopentadienyl ligand structure, cationic active metal types, and cocatalysts on the activity and syndiospecificity of mono-Cp' metallocene catalysts are briefly surveyed.

Microbial carbohydrate-active enzymes influence soil carbon by regulating the of plant- and fungal-derived biomass decomposition in plateau peat wetlands under differing water conditions.

Peatlands are important carbon sinks and water sources in terrestrial ecosystems. It is important to explore their microbial-driven water-carbon synergistic mechanisms to understand the driving mechanisms of carbon processes in peatlands. Based on macrogenomic sequencing techniques, located on the peatland of the eastern margin of the Tibetan Plateau with similar stand and different water conditions, we taken soil properties, microbiome abundance, CAZyme abundance and enzyme gene pathways as the object of study, investigated the characterization of soil microbial carbohydrate-active enzymes (CAZymes) under different water gradients in peatland. According to the results, these three phyla (Chloroflexi, Gemmatimonadetes, and Verrucomicrobia) differed significantly between water gradients. Under dried wetlands, the abundance of CAZymes involved in hemicellulose and glucan degradation increased by 3.0 × 10-5 and 3.0 × 10-6, respectively. In contrast, the abundance of CAZymes involved in chitin degradation decreased by 1.1 × 10-5 (p < 0.05). It highlights that regulating plant- and fungus-derived carbon metabolism processes by soil microorganisms in highland peatlands is a crucial mechanism for their response to water changes. Most plant-derived carbon fractions are regulated by soil enzymes (endo-beta 1,4-xylanase, alpha-L-arabinofuranosidase, and alpha-L-fucosidase) containing CAZymes functional genes. Additional findings in this enzyme gene pathway indicate that water changes that affect soil carbon fractions indirectly influence the three enzyme gene metabolic pathways related to plant carbon sources (the glycolysis/gluconeogenesis, other glycan degradation and amino sugar, and nucleotide sugar metabolism). Overall, this study highlights the significance of microbial CAZymes in highland peatland soil carbon processes and indicates that microbial conversion of plant and fungal biomass carbon is more sensitive to water changes.

The effects of gestational diabetes mellitus on fetal growth: is it different for low-risk and medium-high-risk pregnant women?

BACKGROUND: It has been suggested that gestational diabetes mellitus (GDM) alters the growth trajectory of a fetus and increases the risk of abnormal birth weight. In spite of this, there is still a significant debate regarding the mode and optimal timing of diagnosing this condition. Our aim was to determine fetal growth velocity and birth biometry in pregnant women with GDM at varying risk levels. METHODS: We conducted a cohort study involving 1023 pregnant women at a maternity hospital in Ma'anshan, China. All women completed an oral glucose tolerance test at 24-28 weeks' gestation. We measured fetal head circumference (HC), femoral length (FL), abdominal circumference (AC), biparietal diameter (BPD), and estimate fetal weight (EFW) by ultrasound at 17, 24, 31, and 35 weeks' gestation, respectively. RESULTS: Overall, 5115 ultrasound scans were performed. Among both low-risk and medium-high-risk pregnant women at 17-24 weeks' gestation, GDM exposure was associated with an increase in fetal growth velocity. Neonates born to women with GDM at medium-high risk had significantly larger birth weights than those born to women without GDM, while this was not observed in women at low risk. CONCLUSION: In medium-high-risk pregnant women, exposure to GDM has a greater effect on the fetus, leading to abnormal fetal growth velocity that lasts beyond week 24. It is evident from our results that the effects of GDM on fetal growth differ between medium-high-risk pregnant women and low-risk pregnant women, and therefore a different screening program based on the risk factor for GDM is warranted.

Interferon-stimulated gene 15 facilitates BTV replication through interacting with the NS1 protein.

Bluetongue virus (BTV) infection effectively activates the innate immune response, followed by the expression of interferon (IFN) and multiple interferon-stimulated genes (ISGs). ISG15 is one of the most induced ISGs, and often plays a role in inhibiting virus replication. This study aims to explore the role and specific mechanisms of ovine ISG15 (oISG15) in BTV infection. We found that the transcription level of oISG15 was upregulated in a time-dependent and BTV multiplicity of infection-dependent manner. The overexpression of exogenous oISG15 enhances BTV replication, whereas the knockdown of endogenous oISG15 inhibits BTV replication. The viral protein in wild-type oISG15-overexpressed cells and ISGylation defective oISG15-overexpressed cells have no significant differences, which indicated that oISG15 promoted BTV replication in an ISGylation-independent manner. A co-immunoprecipitation assay showed that four viral BTV proteins-VP3, VP4, VP5, and NS1-interacted with oISG15. We also found that the VP4 and NS1 proteins associated with ubiquitin via co-immunoprecipitation, and that oISG15 overexpression improved the stability of both proteins. Further results showed that the degradation of NS1 was involved in lysine 63-linked polyubiquitin. This suggested that oISG15 may interfere with NS1 degradation via the autophagy pathway. This study provides new insights on the interaction between BTV and ISG15, and enriches our understanding of the regulation and biological function of ISG15 with virus replication.

Brain-wide representations of behavior spanning multiple timescales and states in C. elegans.

Changes in an animal's behavior and internal state are accompanied by widespread changes in activity across its brain. However, how neurons across the brain encode behavior and how this is impacted by state is poorly understood. We recorded brain-wide activity and the diverse motor programs of freely moving C. elegans and built probabilistic models that explain how each neuron encodes quantitative behavioral features. By determining the identities of the recorded neurons, we created an atlas of how the defined neuron classes in the C. elegans connectome encode behavior. Many neuron classes have conjunctive representations of multiple behaviors. Moreover, although many neurons encode current motor actions, others integrate recent actions. Changes in behavioral state are accompanied by widespread changes in how neurons encode behavior, and we identify these flexible nodes in the connectome. Our results provide a global map of how the cell types across an animal's brain encode its behavior.

The modification of meteorological factors on the relationship between air pollution and periodontal diseases: an exploration based on different interaction strategies.

We aimed to characterize the association between air pollutants exposure and periodontal diseases outpatient visits and to explore the interactions between ambient air pollutants and meteorological factors. The outpatient visits data of several large stomatological and general hospitals in Hefei during 2015-2020 were collected to explore the relationship between daily air pollutants exposure and periodontal diseases by combining Poisson's generalized linear model (GLMs) and distributed lag nonlinear model (DLNMs). Subgroup analysis was performed to identify the vulnerability of different populations to air pollutants exposure. The interaction between air pollutants and meteorological factors was verified in both multiplicative and additive interaction models. An interquartile range (IQR) increased in nitrogen dioxide (NO2) concentration was associated with the greatest lag-specific relative risk (RR) of gingivitis at lag 3 days (RR = 1.087, 95% CI 1.008-1.173). Fine particulate matter (PM2.5) exposure also increased the risk of periodontitis at the day of exposure (RR = 1.049, 95% CI 1.004-1.096). Elderly patients with gingivitis and periodontitis were both vulnerable to PM2.5 exposure. The interaction analyses showed that exposure to high levels of NO2 at low temperatures was related to an increased risk of gingivitis, while exposure to high levels of NO2 and PM2.5 may also increase the risk of gingivitis and periodontitis in the high-humidity environment, respectively. This study supported that NO2 and PM2.5 exposure increased the risk of gingivitis and periodontitis outpatient visits, respectively. Besides, the adverse effects of air pollutants exposure on periodontal diseases may vary depending on ambient temperature and humidity.

Design, synthesis, and biological evaluation of a series of indolone derivatives as novel FLT3 inhibitors for the treatment of acute myeloid leukemia.

FLT3-ITD mutant has been extensively studied as a drug discovery target for acute myeloid leukemia. Based on our previous discovered FLT3 inhibitor (2), a series of urea group based indolone derivatives were designed, synthesized, and biological evaluated as novel FLT3 inhibitors for the treatment of FLT3-ITD positive AML. Among them, compound LC-3 exhibited potent inhibitory effects against FLT3 (IC50 = 8.4 nM) and significantly inhibited the proliferation of FLT3-ITD positive AML cells MV-4-11 (IC50 = 5.3 nM). In the cellular context, LC-3 strongly inhibited FLT3-mediated signaling pathways and induced cellular apoptosis by arresting cell cycle in G1 phase. In the in vivo studies, LC-3 significantly suppressed the tumor growth on MV-4-11 xenograft models (10 mg/kg/day, TGI = 92.16%) without exhibiting obvious toxicity. These results suggested that compound LC-3 might be a potential drug candidate for FLT3-ITD positive AML.

Malignant pleural mesothelioma with constrictive pericarditis as the first manifestation: A case report.

Pleural mesothelioma (PM) with pericardial involvement is extremely rare. We now report a rare case of malignant PM with constrictive pericarditis as the first presentation. A 59-year-old male diagnosed with constrictive pericarditis underwent pericardiectomy and pericardial pathology revealed mesothelial hyperplasia. Eight months after surgery, the patient was admitted to the hospital with chest tightness and wheezing for 5 days. Computed tomography scan of the chest showed a left lung expansion insufficiency, limited bilateral pleural thickening, pericardial thickening with a small amount of pericardial effusion, and multiple enlarged lymph nodes in the mediastinum, bilateral supraclavicular fossa, bilateral cervical roots, and right axilla. The pleural malignancy should be possibly considered. Pathology after pleural puncture showed malignant PM. Pathology after left supraclavicular lymph node puncture biopsy showed metastatic malignant mesothelioma. The diagnosis of this patient was clear. Although malignant PM rarely involves the pericardial constriction, we cannot ignore the fact that malignant PM involves the pericardium. The patient has been diagnosed with constrictive pericarditis, accompanied by pleural thickening and pleural effusion. Without other pathogenic factors, pleural biopsy should be aggressively performed in patients with constrictive pericarditis to determine the cause.

Clinicopathological characteristics and outcomes of lupus nephritis patients with scanty immune depositions in kidney biopsies.

BACKGROUND: The clinicopathological features, outcomes, and pathogenesis of lupus nephritis with scanty immune deposits in the kidney biopsy remain unclear. METHODS: Four hundred ninety-eight biopsy-proven lupus nephritis patients were included, and clinical and pathological data were collected. The primary endpoint was mortality, while the secondary endpoint was doubling baseline serum creatinine or end-stage renal disease. Associations between scanty immune deposits lupus nephritis and adverse outcomes were analyzed by Cox regression models. RESULTS: Among 498 lupus nephritis patients, 81 were diagnosed with scanty immune deposits. Patients with scanty immune deposits had significantly higher serum albumin and serum complement C4 than those with immune complex deposits. The proportion of anti-neutrophil cytoplasmic antibodies was similar between the two groups. In addition, patients with scanty immune deposits showed less proliferative features at kidney biopsy and lower activity index score, accompanied by milder mesangial cell and matrix hyperplasia, endothelial cell hyperplasia, nuclear fragmentation, and glomerular leukocyte infiltration. Patients in this group also had a milder degree of foot process fusion. Overall, renal survival and patient survival showed no significant difference between the two groups. 24-h proteinuria and chronicity index were significant risk factors for renal survival, and 24-h proteinuria and positive anti-neutrophil cytoplasmic antibodies were risk factors for patient survival in scanty immune deposits lupus nephritis patients. CONCLUSIONS: Compared with other lupus nephritis patients, scanty immune deposits lupus nephritis patients had significantly lower activity features on kidney biopsy, but have similar outcomes. Positive anti-neutrophil cytoplasmic antibodies may be a risk factor for patient survival in scanty immune deposits lupus nephritis patients.

Dissecting the functional organization of the C. elegans serotonergic system at whole-brain scale.

Serotonin influences many aspects of animal behavior. But how serotonin acts on its diverse receptors across the brain to modulate global activity and behavior is unknown. Here, we examine how serotonin release in C. elegans alters brain-wide activity to induce foraging behaviors, like slow locomotion and increased feeding. Comprehensive genetic analyses identify three core serotonin receptors (MOD-1, SER-4, and LGC-50) that induce slow locomotion upon serotonin release and others (SER-1, SER-5, and SER-7) that interact with them to modulate this behavior. SER-4 induces behavioral responses to sudden increases in serotonin release, whereas MOD-1 induces responses to persistent release. Whole-brain imaging reveals widespread serotonin-associated brain dynamics, spanning many behavioral networks. We map all sites of serotonin receptor expression in the connectome, which, together with synaptic connectivity, helps predict which neurons show serotonin-associated activity. These results reveal how serotonin acts at defined sites across a connectome to modulate brain-wide activity and behavior.

Audio2Gestures: Generating Diverse Gestures From Audio.

People may perform diverse gestures affected by various mental and physical factors when speaking the same sentences. This inherent one-to-many relationship makes co-speech gesture generation from audio particularly challenging. Conventional CNNs/RNNs assume one-to-one mapping, and thus tend to predict the average of all possible target motions, easily resulting in plain/boring motions during inference. So we propose to explicitly model the one-to-many audio-to-motion mapping by splitting the cross-modal latent code into shared code and motion-specific code. The shared code is expected to be responsible for the motion component that is more correlated to the audio while the motion-specific code is expected to capture diverse motion information that is more independent of the audio. However, splitting the latent code into two parts poses extra training difficulties. Several crucial training losses/strategies, including relaxed motion loss, bicycle constraint, and diversity loss, are designed to better train the VAE. Experiments on both 3D and 2D motion datasets verify that our method generates more realistic and diverse motions than previous state-of-the-art methods, quantitatively and qualitatively. Besides, our formulation is compatible with discrete cosine transformation (DCT) modeling and other popular backbones (i.e. RNN, Transformer). As for motion losses and quantitative motion evaluation, we find structured losses/metrics (e.g. STFT) that consider temporal and/or spatial context complement the most commonly used point-wise losses (e.g. PCK), resulting in better motion dynamics and more nuanced motion details. Finally, we demonstrate that our method can be readily used to generate motion sequences with user-specified motion clips on the timeline.

Representation-Learning-Based CNN for Intelligent Attack Localization and Recovery of Cyber-Physical Power Systems.

Enabled by the advances in communication networks, computational units, and control systems, cyber-physical power systems (CPPSs) are anticipated to be complex and smart systems in which a large amount of data are generated, exchanged, and processed for various purposes. Due to these strong interactions, CPPSs will introduce new security vulnerabilities. To ensure secure operation and control of CPPSs, it is essential to detect the locations of the attacked measurements and remove the state bias caused by malicious cyber-attacks such as false data inject attack, jamming attack, denial of service attack, or hybrid attack. Accordingly, this article makes the first contribution concerning the representation-learning-based convolutional neural network (RL-CNN) for intelligent attack localization and system recovery of CPPSs. In the proposed method, the cyber-attacks' locational detection problem is formulated as a multilabel classification problem for CPPSs. An RL-CNN is originally adopted as the multilabel classifier to explore and exploit the implicit information of measurements. By comparing with previous multilabel classifiers, the RL-CNN improves the performance of attack localization for complex CPPSs. Then, to automatically filter out the cyber-attacks for system recovery, a mean-squared estimator is used to handle the difficulty in state estimation with the removal of contaminated measurements. In this scheme, prior knowledge of the system state is obtained based on the outputs of the stochastic power flow or historical measurements. The extensive simulation results in three IEEE bus systems show that the proposed method is able to provide high accuracy for attack localization and perform automatic attack filtering for system recovery under various cyber-attacks.