bluuebunny/crossref_metadata_2025 huggingface dataset:
Controlled sequential in situ self-assembly and disassembly of a fluorogenic cisplatin prodrug for cancer theranostics
Authors: Wen Xidan , Zhang Rui , Hu Yuxuan , Wu Luyan , Bai He , Song Dongfan , Wang Yanfeng , An Ruibing , Weng Jianhui , Zhang Shuren , Wang Rong , Qiu Ling , Lin Jianguo , Gao Guandao , Liu Hong , Guo Zijian , Ye Deju
Published: February 2023

Temporal control of delivery and release of drugs in tumors are important in improving therapeutic outcomes to patients. Here, we report a sequential stimuli-triggered in situ self-assembly and disassembly strategy to direct delivery and release of theranostic drugs in vivo. Using cisplatin as a model anticancer drug, we design a stimuli-responsive small-molecule cisplatin prodrug (P-CyPt), which undergoes extracellular alkaline phosphatase-triggered in situ self-assembly and succeeding intracellular glutathione-triggered disassembly process, allowing to enhance accumulation and elicit burst release of cisplatin in tumor cells. Compared with cisplatin, P-CyPt greatly improves antitumor efficacy while mitigates off-target toxicity in mice with subcutaneous HeLa tumors and orthotopic HepG2 liver tumors after systemic administration. Moreover, P-CyPt also produces activated near-infrared fluorescence (at 710 nm) and dual photoacoustic imaging signals (at 700 and 750 nm), permitting high sensitivity and spatial-resolution delineation of tumor foci and real-time monitoring of drug delivery and release in vivo. This strategy leverages the advantages offered by in situ self-assembly with those of intracellular disassembly, which may act as a general platform for the design of prodrugs capable of improving drug delivery for cancer theranostics.
Creation of chiral interface channels for quantized transport in magnetic topological insulator multilayer heterostructures
Authors: Zhao Yi-Fan , Zhang Ruoxi , Cai Jiaqi , Zhuo Deyi , Zhou Ling-Jie , Yan Zi-Jie , Chan Moses H. W. , Xu Xiaodong , Chang Cui-Zu
Published: February 2023

One-dimensional chiral interface channels can be created at the boundary of two quantum anomalous Hall (QAH) insulators with different Chern numbers. Such a QAH junction may function as a chiral edge current distributer at zero magnetic field, but its realization remains challenging. Here, by employing an in-situ mechanical mask, we use molecular beam epitaxy to synthesize QAH insulator junctions, in which two QAH insulators with different Chern numbers are connected along a one-dimensional junction. For the junction between Chern numbers of 1 and −1, we observe quantized transport and demonstrate the appearance of the two parallel propagating chiral interface channels along the magnetic domain wall at zero magnetic field. For the junction between Chern numbers of 1 and 2, our quantized transport shows that a single chiral interface channel appears at the interface. Our work lays the foundation for the development of QAH insulator-based electronic and spintronic devices and topological chiral networks.
A latitudinal gradient of deep-sea invasions for marine fishes
Authors: Friedman Sarah T. , Muñoz Martha M.
Published: February 2023

Although the tropics harbor the greatest species richness globally, recent work has demonstrated that, for many taxa, speciation rates are faster at higher latitudes. Here, we explore lability in oceanic depth as a potential mechanism for this pattern in the most biodiverse vertebrates – fishes. We demonstrate that clades with the highest speciation rates also diversify more rapidly along the depth gradient, drawing a fundamental link between evolutionary and ecological processes on a global scale. Crucially, these same clades also inhabit higher latitudes, creating a prevailing latitudinal gradient of deep-sea invasions concentrated in poleward regions. We interpret these findings in the light of classic ecological theory, unifying the latitudinal variation of oceanic features and the physiological tolerances of the species living there. This work advances the understanding of how niche lability sculpts global patterns of species distributions and underscores the vulnerability of polar ecosystems to changing environmental conditions.
Photonic comb-rooted synthesis of ultra-stable terahertz frequencies
Authors: Shin Dong-Chel , Kim Byung Soo , Jang Heesuk , Kim Young-Jin , Kim Seung-Woo
Published: February 2023

Stable terahertz sources are required to advance high-precision terahertz applications such as molecular spectroscopy, terahertz radars, and wireless communications. Here, we demonstrate a photonic scheme of terahertz synthesis devised to bring the well-established feat of optical frequency comb stabilization down to the terahertz region. The source comb is stabilized to an ultra-low expansion optical cavity offering a frequency instability of 10−15 at 1-s integration. By photomixing a pair of comb lines extracted coherently from the source comb, terahertz frequencies of 0.10–1.10 THz are generated with an extremely low level of phase noise of –70 dBc/Hz at 1-Hz offset. The frequency instability measured for 0.66 THz is 4.4 × 10−15 at 1-s integration, which reduces to 5.1×10−17 at 65-s integration. Such unprecedented performance is expected to drastically improve the signal-to-noise ratio of terahertz radars, the resolving power of terahertz molecular spectroscopy, and the transmission capacity of wireless communications.
A cooperative nano-CRISPR scaffold potentiates immunotherapy via activation of tumour-intrinsic pyroptosis
Authors: Wang Ning , Liu Chao , Li Yingjie , Huang Dongxue , Wu Xinyue , Kou Xiaorong , Wang Xiye , Wu Qinjie , Gong Changyang
Published: February 2023

Efficient cancer immunotherapy depends on selective targeting of high bioactivity therapeutic agents to the tumours. However, delivering exogenous medication might prove difficult in clinical practice. Here we report a cooperative Nano-CRISPR scaffold (Nano-CD) that utilizes a specific sgRNA, selected from a functional screen for triggering endogenous GDSME expression, while releasing cisplatin to initiate immunologic cell death. Mechanistically, cascade-amplification of the antitumor immune response is prompted by the adjuvantic properties of the lytic intracellular content and enhanced by the heightened GDSME expression, resulting in pyroptosis and the release of tumor associated antigens. Neither of the single components provide efficient tumour control, while tumor growth is efficiently inhibited in primary and recurrent melanomas due to the combinatorial effect of cisplatin and self-supplied GSDME. Moreover, Nano-CD in combination with checkpoint blockade creates durable immune memory and strong systemic anti-tumor immune response, leading to disease relapse prevention, lung metastasis inhibition and increased survival in mouse melanomas. Taken together, our therapeutic approach utilizes CRISPR-technology to enable cell-intrinsic protein expression for immunotherapy, using GDSME as prototypic immune modulator. This nanoplatform thus can be applied to modulate further immunological processes for therapeutic benefit.
Murine neonatal cardiac B cells promote cardiomyocyte proliferation and heart regeneration
Authors: Tan Yong , Duan Xuewen , Wang Bo , Liu Xingguang , Zhan Zhenzhen
Published: February 2023

The irreversible loss of cardiomyocytes in the adult heart following cardiac injury leads to adverse cardiac remodeling and ventricular dysfunction. However, the role of B cells in cardiomyocyte proliferation and heart regeneration has not been clarified. Here, we found that the neonatal mice with B cell depletion showed markedly reduced cardiomyocyte proliferation, leading to cardiac dysfunction, fibrosis scar formation, and the complete failure of heart regeneration after apical resection. B cell depletion also significantly impaired heart regeneration and cardiac function in neonatal mice following myocardial infarction (MI). However, B cell depletion in adult mice suppressed tissue inflammation, inhibited myocardial fibrosis, and improved cardiac function after MI. Interestingly, B cell depletion partially restricted cardiomyocyte proliferation in adult mice post-MI. Single-cell RNA sequencing showed that cardiac B cells possessed a more powerful ability to inhibit inflammatory responses and enhance angiogenesis in the postnatal day 1 (P1) mice compared with P7 and adult mice. Besides, the proportion of cardioprotective B cell clusters with high expression levels of S100a6 (S100 calcium-binding protein A6) and S100a4 (S100 calcium-binding protein A4) was greatly decreased in adult heart tissues compared with neonatal mice after cardiac damage. Thus, our study discovers that cardiac B cells in neonatal mice are required for cardiomyocyte proliferation and heart regeneration, while adult B cells promote inflammation and impair cardiac function after myocardial injury.
Effect and mechanism of NaHS on tobacco bacterial wilt caused by Ralstonia solanacearum
Authors: Wen Dingxin , Guo Qingqing , Zhao Wan , Yang Yong , Yang Chunlei , Yu Jun , Hu Yun
Published: February 2023

Since its discovery as a third unique gaseous signal molecule, hydrogen sulfide (H2S) has been extensively employed to resist stress and control pathogens. Nevertheless, whether H2S can prevent tobacco bacterial wilt is unknown yet. We evaluated the impacts of the H2S donor sodium hydrosulfide (NaHS) on the antibacterial activity, morphology, biofilm, and transcriptome of R. solanacearum to understand the effect and mechanism of NaHS on tobacco bacterial wilt. In vitro, NaHS significantly inhibited the growth of Ralstonia solanacearum and obviously altered its cell morphology. Additionally, NaHS significantly inhibited the biofilm formation and swarming motility of R. solanacearum, and reduced the population of R. solanacearum invading tobacco roots. In field experiments, the application of NaHS dramatically decreased the disease incidence and index of tobacco bacterial wilt, with a control efficiency of up to 89.49%. The application of NaHS also influenced the diversity and structure of the soil microbial community. Furthermore, NaHS markedly increased the relative abundances of beneficial microorganisms, which helps prevent tobacco bacterial wilt. These findings highlight NaHS's potential and efficacy as a powerful antibacterial agent for preventing tobacco bacterial wilt caused by R. solanacearum.
House Sparrow (Passer domesticus) escape behavior is triggered faster in smaller settlements
Authors: García-Arroyo Michelle , MacGregor-Fors Ian , Quesada Javier , Borràs Antoni , Colomé-Menoyo Laia , Senar Juan Carlos
Published: February 2023

A recurrent behavioral trait model to study adaptation to urban environments is the flight initiation distance (FID), measured as the distance at which animals flee from an approaching threat. It has previously been shown that urban birds display shorter FID than their non-urban (rural) counterparts. However, discerning whether this is the result of habituation to human presence and frequentation, or of ecological factors related to the size of the city (considered as “systemic habituation”), has not yet been addressed. In this study, we analyzed House Sparrow (Passer domesticus) FIDs in a network of 26 small towns and villages within the same region in northeastern Spain. Our aim was to relate FID to human population density and settlement size. If the habituation to human presence hypothesis was supported, we should expect FIDs to decrease with the density of the human population across the human settlements, since this type of habituation is related to the rate of human exposure and this is proportional to human density. However, if the systemic habituation hypothesis was supported, FIDs should instead relate to the size of the human settlements, as the abundance of predators, similarly to other ecological variables, is often proportional to the size of towns. Results showed House Sparrows to be bolder in larger human settlements, but not necessarily the ones with a higher density of human population. This supports the idea that the fact that urban birds display shorter FIDs than their rural counterparts is the result of systemic ecological factors rather than the results of a simple habituation to humans.
Incidence and risk factors of opportunistic infections after autologous stem cell transplantation: a nationwide, population-based cohort study in Korea
Authors: Kim Da Jung , Jeong Seri , Kong Seom Gim , Lee Sangjin , Lim Sung-Nam , Oh Sung Yong , Do Young Rok , Lee Won Sik , Lee Mark Hong , Bae Sung Hwa , Kim Se Hyung , Kim Min Kyoung , Lee Ho Sup ,   Consortium for Improving Survival of Lymphoma (CISL)
Published: February 2023

Several guidelines classify autologous stem cell transplantation (ASCT) as a low to intermediate risk group for infection. In a nationwide population-based study, using the Korean Health Insurance Review and Assessment Service database, patients with lymphoma and multiple myeloma (MM) who underwent ASCT from 2002 to 2016 were retrospectively analyzed. Cumulative incidence rates (CIRs) and risk factors of opportunistic infections were investigated. CIRs of fungal, Varicella zoster virus (VZV), cytomegalovirus (CMV), and Pneumocystis jirovecii infections in lymphoma were 7.9%, 16.0%, 7.4%, and 5.1%, respectively, and CIRs in MM were 6.3%, 19.1%, 4.2%, and 5.6%, respectively. Fungal infection was significantly higher in patients with previous infection (Hazard ratio (HR) 2.003, p = 0.005) in lymphoma. Incidence of CMV infection was significantly higher in patients with prior CMV infection: HR 4.920, p < 0.001 (lymphoma); HR 3.022, p = 0.030 (MM). VZV infection was significantly lower in patients receiving prophylaxis: HR 0.082, p < 0.001 (lymphoma); HR 0.096, p < 0.001 (MM). For P. jirovecii infection, busulfex and melphalan conditioning (HR 1.875, p = 0.032) and previous P. jirovecii infection (HR 4.810, p < 0.001) had a higher incidence in MM. Patients who underwent ASCT should receive VZV prophylaxis and prophylaxis for fungal and P. jirovecii may be considered in patients with previous same infection.
Prevalence, awareness, treatment, and control of hypertension and their risk factors in Shaanxi Province in 2004–18
Authors: Wang Weihua , Sa Rina , Dang Shaonong , Qiu Lin , Liu Feng
Published: February 2023

To investigate trends in the prevalence, awareness, treatment and control of hypertension and their demographic determinants in Shaanxi Province. Six successive cross-sectional surveys on non-communicable chronic diseases and their risk factors were conducted between 2004 and 2018 in Shaanxi. Complex multistage stratified sampling was adopted to select participants. The information was collected through face-to-face interviews and on-site health examinations. Changes in hypertension prevalence and its management across survey years were estimated. Demographics associated with hypertension prevalence and its management was explored by multivariable logistic regression using pooled data from 2004 to 2018. The prevalence of hypertension increased from 16.71% in 2004 to 31.96% in 2018 with an estimated increase of 1.09% (95% CI 0.31–1.87) per year. However, the rate of awareness, treatment and control among these with hypertension was unexpectedly low and there were no significant change from 2004 to 2018. The corresponding changes were − 0.08% (95% CI − 0.85–0.69) per year for awareness, − 0.06% (95% CI − 1.11–1.00) per year for treatment, and − 0.23% (95% CI − 0.53–0.07) per year for control, respectively. Sensitivity analysis showed the same trend. Adults who were old, male, divorced/Widowed/Separated, retired were more likely to develop hypertension. Among these with hypertension, those who were more educated and retired were more likely to manage their hypertension compared with their counterparts. The overall hypertension prevalence from 2004 to 2018 increased rapidly, while awareness, treatment and control of hypertension remained unexpectedly low. This suggested urgent intervention should be implemented to improve hypertension control in Shaanxi Province.
Global conservation prioritization areas in three dimensions of crocodilian diversity
Authors: Lourenço-de-Moraes Ricardo , Campos Felipe S. , Cabral Pedro , Silva-Soares Thiago , Nobrega Yhuri C. , Covre Amanda C. , França Frederico G. R.
Published: February 2023

Crocodilians are a taxonomic group of large predators with important ecological and evolutionary benefits for ecosystem functioning in the face of global change. Anthropogenic actions affect negatively crocodilians’ survival and more than half of the species are threatened with extinction worldwide. Here, we map and explore three dimensions of crocodilian diversity on a global scale. To highlight the ecological importance of crocodilians, we correlate the spatial distribution of species with the ecosystem services of nutrient retention in the world. We calculate the effectiveness of global protected networks in safeguarding crocodilian species and provide three prioritization models for conservation planning. Our results show the main hotspots of ecological and evolutionary values are in southern North, Central and South America, west-central Africa, northeastern India, and southeastern Asia. African species have the highest correlation to nutrient retention patterns. Twenty-five percent of the world’s crocodilian species are not significantly represented in the existing protected area networks. The most alarming cases are reported in northeastern India, eastern China, and west-central Africa, which include threatened species with low or non-significant representation in the protected area networks. Our highest conservation prioritization model targets southern North America, east-central Central America, northern South America, west-central Africa, northeastern India, eastern China, southern Laos, Cambodia, and some points in southeastern Asia. Our research provides a global prioritization scheme to protect multiple dimensions of crocodilian diversity for achieving effective conservation outcomes.
RETRACTED ARTICLE: Mechanism of arterial injury
exacerbated by hyperhomocysteinemia in spontaneously hypertensive rats
Authors: Zhang Lihua , Xu Rui , Ma Xiaoshan , Zhang Xia , Gong Jun , Li Zhongliang
Published: February 2023

Hypertension associated with hyperhomocysteinemia (HHcy) accounts for 75%
of hypertension in China. HHcy plays a synergistic role with hypertension in vascular
injury and significantly increases the incidence of cardiovascular and cerebrovascular
diseases. The present study aimed to explore the molecular mechanism of HHcy-induced
arterial injury in hypertension. Spontaneously hypertensive rats (SHR) were injected
intraperitoneally with DL-homocysteine (Hcy) to construct the model of hypertension
associated with HHcy (HHcy + SHR). Biological network was employed to identify the
material basis of arterial injury in hypertension associated with HHcy. The prediction
molecules in oxidative stress and inflammation pathways were experimentally verified by
quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB)
analysis. The HHcy + SHR group significantly increased oxidative stress pathway
molecules: nicotinamide adenine dinucleotide phosphate oxidase (Nox); inflammatory
pathway molecules: vascular adhesion protein-1 (VAP-1), interleukin-6 (IL-6) and tumor
necrosis factor-alpha (TNF-a); as well as inflammatory pathway regulatory factors:
nuclear factor-κ-gene binding (NF-κB) p65 and protein kinase B (Akt1). Among them, IL-6
was also significantly increased in the HHcy group. Both oxidative stress and
inflammation contributed to the arterial injury of hypertension associated with HHcy,
and inflammation mechanism might play a leading role in HHcy aggravating arterial
injury, at least partially through the Akt1/NF-κB p65/IL-6 signaling pathway.
Structure–function assessment in glaucoma based on perimetric sensitivity and en face optical coherence tomography images of retinal nerve fiber bundles
Authors: Alluwimi Muhammed S. , Swanson William H. , Malik Rizwan
Published: February 2023

Many studies have assessed structure–function relations in glaucoma, but most without topographical comparison across the central 30°. We present a method for assessing structure–function relations with en face images of retinal nerve fiber layer (RNFL) bundles allowing topographical comparison across much of this retinal area. Forty-four patients with glaucoma (median age 61 years) were recruited and tested with Optical Coherence Tomography (OCT) and perimetry. Six rectangular volume scans were gathered, and then montaged to provide en face views of the RNFL bundles. We calculated the proportion of locations showing a perimetric defect that also showed an en face RNFL defect; and the proportion of locations falling on an RNFL defect that also showed a perimetric defect. A perimetric defect for a location was defined as a total deviation (TD) value equal to or deeper than -4 dB. We found that the median (IQR) number of locations with abnormal RNFL bundle reflectance that also had abnormal TD was 78% (60%) and for locations with abnormal TD that also had abnormal RNFL bundle reflectance was 75% (44%). We demonstrated a potential approach for structure–function assessment in glaucoma by presenting a topographic reflectance map, confirming results of previous studies and including larger retinal regions.
Detection of acute promyelocytic leukemia in peripheral blood and bone marrow with annotation-free deep learning
Authors: Manescu Petru , Narayanan Priya , Bendkowski Christopher , Elmi Muna , Claveau Remy , Pawar Vijay , Brown Biobele J. , Shaw Mike , Rao Anupama , Fernandez-Reyes Delmiro
Published: February 2023

While optical microscopy inspection of blood films and bone marrow aspirates by a hematologist is a crucial step in establishing diagnosis of acute leukemia, especially in low-resource settings where other diagnostic modalities are not available, the task remains time-consuming and prone to human inconsistencies. This has an impact especially in cases of Acute Promyelocytic Leukemia (APL) that require urgent treatment. Integration of automated computational hematopathology into clinical workflows can improve the throughput of these services and reduce cognitive human error. However, a major bottleneck in deploying such systems is a lack of sufficient cell morphological object-labels annotations to train deep learning models. We overcome this by leveraging patient diagnostic labels to train weakly-supervised models that detect different types of acute leukemia. We introduce a deep learning approach, Multiple Instance Learning for Leukocyte Identification (MILLIE), able to perform automated reliable analysis of blood films with minimal supervision. Without being trained to classify individual cells, MILLIE differentiates between acute lymphoblastic and myeloblastic leukemia in blood films. More importantly, MILLIE detects APL in blood films (AUC 0.94 ± 0.04) and in bone marrow aspirates (AUC 0.99 ± 0.01). MILLIE is a viable solution to augment the throughput of clinical pathways that require assessment of blood film microscopy.
Tanshinone IIA-loaded nanoparticles and neural stem cell combination therapy improves gut homeostasis and recovery in a pig ischemic stroke model
Authors: Jeon Julie H. , Kaiser Erin E. , Waters Elizabeth S. , Yang Xueyuan , Lourenco Jeferson M. , Fagan Madison M. , Scheulin Kelly M. , Sneed Sydney E. , Shin Soo K. , Kinder Holly A. , Kumar Anil , Platt Simon R. , Ahn Jeongyoun , Duberstein Kylee J. , Rothrock Michael J. , Callaway Todd R. , Xie Jin , West Franklin D. , Park Hea Jin
Published: February 2023

Impaired gut homeostasis is associated with stroke often presenting with leaky gut syndrome and increased gut, brain, and systemic inflammation that further exacerbates brain damage. We previously reported that intracisternal administration of Tanshinone IIA-loaded nanoparticles (Tan IIA-NPs) and transplantation of induced pluripotent stem cell-derived neural stem cells (iNSCs) led to enhanced neuroprotective and regenerative activity and improved recovery in a pig stroke model. We hypothesized that Tan IIA-NP + iNSC combination therapy-mediated stroke recovery may also have an impact on gut inflammation and integrity in the stroke pigs. Ischemic stroke was induced, and male Yucatan pigs received PBS + PBS (Control, n = 6) or Tan IIA-NP + iNSC (Treatment, n = 6) treatment. The Tan IIA-NP + iNSC treatment reduced expression of jejunal TNF-α, TNF-α receptor1, and phosphorylated IkBα while increasing the expression of jejunal occludin, claudin1, and ZO-1 at 12 weeks post-treatment (PT). Treated pigs had higher fecal short-chain fatty acid (SCFAs) levels than their counterparts throughout the study period, and fecal SCFAs levels were negatively correlated with jejunal inflammation. Interestingly, fecal SCFAs levels were also negatively correlated with brain lesion volume and midline shift at 12 weeks PT. Collectively, the anti-inflammatory and neuroregenerative treatment resulted in increased SCFAs levels, tight junction protein expression, and decreased inflammation in the gut.
Different risk factors distinguish myalgic encephalomyelitis/chronic fatigue syndrome from severe fatigue
Authors: Palacios Natalia , Molsberry Samantha , Fitzgerald Kathryn C. , Komaroff Anthony L.
Published: February 2023

Fatigue is a common reason that patients seek medical care. Only a fraction of these patients meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). To determine if ME/CFS is just a more extreme form of fatigue, or a qualitatively different condition, we assessed whether risk factors for ME/CFS and for Severe Fatigue were similar. An email questionnaire that inquired about symptoms of Severe Fatigue and ME/CFS was completed by 41,802 US female nurses from whom detailed medical and lifestyle information had been collected since 1989: 102 met criteria for ME/CFS, 522 had Severe Fatigue, and 41,178 individuals were without significant chronic fatigue. We used Cox proportional hazards regression to estimate the Hazard Ratio (HR) of Severe Fatigue and of ME/CFS with each of several potential risk factors, according to the level of exposure to each risk factor. The risk of Severe Fatigue was significantly increased among participants who were older, had a higher BMI in adulthood, used hormone therapy, had increased alcohol intake and decreased caffeine intake. In contrast, these risk factor associations were not seen in people with ME/CFS. A self-reported past history of acute infectious mononucleosis was associated with a non-significantly increased Hazard Ratio of later ME/CFS (HR 1.77, 0.87–3.61) and, to a lesser extent, of Severe Fatigue (HR 1.28, 0.98–1.66). The different contribution of various risk factors to Severe Fatigue and ME/CFS suggests that ME/CFS has a qualitatively different underlying biology from the more common state of Severe Fatigue.
Activation of the rostral nucleus accumbens shell by optogenetics induces cataplexy-like behavior in orexin neuron-ablated mice
Authors: Kawashima Shigetaka , Lou Fan , Kusumoto-Yoshida Ikue , Hao Liying , Kuwaki Tomoyuki
Published: February 2023

Cataplexy is one of the symptoms of type 1 narcolepsy, characterized by a sudden loss of muscle tone. It can be seen as a behavioral index of salience, predominantly positive emotion, since it is triggered by laughter in humans and palatable foods in mice. In our previous study using chemogenetic techniques in narcoleptic mice (orexin neuron-ablated mice), we found that the rostral nucleus accumbens (NAc) shell is needed for chocolate-induced cataplexy. In this study, we investigated whether a short-lasting stimulation/inhibition of the NAc by optogenetics led to a similar result. Photo-illumination to the NAc in the channel rhodopsin-expressing mice showed a higher incidence (34.9 ± 5.1%) of cataplexy-like behavior than the control mice (17.8 ± 3.1%, P = 0.0056). Meanwhile, inactivation with archaerhodopsin did not affect incidence. The episode duration of cataplexy-like behavior was not affected by activation or inactivation. Immunohistochemical analysis revealed that photo-illumination activated channel rhodopsin-expressing NAc shell neurons. Thus, activation of the NAc, whether transient (light stimulation) or longer-lasting (chemical stimulation in our previous study), facilitates cataplexy-like behaviors and contributes to the induction but not maintenance in them. On the other hand, our study's result from optogenetic inhibition of the NAc (no effect) was different from chemogenetic inhibition (reduction of cataplexy-like behavior) in our previous study. We propose that the initiation of cataplexy-like behavior is facilitated by activation of the NAc, while NAc-independent mechanisms determine the termination of the behavior.
Study of snow cover/depth evolution characteristics in Tianshan region of China based on geographical partition
Authors: Qiao Wei , Xie Liangfu , Zhang Jiabing , Qin Yongjun , Liu Xuejun
Published: February 2023

Based on the digital elevation data, snow depth and snow cover remote sensing data, this paper divides six snow evolution areas and geographical partitions, extracts the geographical partitions of each evolution area and obtains the geographical characteristics of the evolution area for analysis. The results show that: (1) From 2003 to 2017, the average snow area decreased at a rate of − 0.004, and the average snow depth increased at a rate of 0.03. (2) The snow in the middle altitude hill with shady gentle slope area is the most obvious in the seasonal evolution, and the percentage of this region in the seasonal snow evolution area is 5.46%, the snow depth in the middle altitude hill with sunny and gentle slopes area increased and decreased significantly in the past 15 years, and the percentage of this region in the SD significant changes evolution area was 6.32%. The snow in the low relief middle altitude mountain with shady and moderate slope area not only shows obvious seasonal evolution, but also increases and decreases significantly in snow depth. And the percentage of this region in the seasonal snow significant evolution area is 5.82%. (3) The geographical partitions with the largest area in all evolution areas is the middle altitude hill with sunny and gentle slopes area (4.75%). (4) The geographical partition with the largest variation of snow depth in Tianshan region is the low relief middle altitude mountain with shady and moderate slope area (12.02 cm). (5) The snow accumulation and melting are obvious in the range of 1000–3500 m above altitude, different geomorphology types lead to obvious differences in snow characteristics. The snow melting is most obvious in the gentle slope area of the low topographic relief geomorphology types, and the snow accumulation is most obvious in the steep slope area of the middle relief geomorphology types.
Political ideology and moral dilemmas in public good provision
Authors: Hoenig Laura C. , Pliskin Ruthie , De Dreu Carsten K. W.
Published: February 2023

Individuals often face dilemmas in which non-cooperation serves their self-interest and cooperation favors society at large. Cooperation is often considered the moral choice because it creates equality and fairness among citizens. Accordingly, individuals whose political ideology attaches greater value to equality than to agency and self-reliance should not only cooperate on more rather than less efficient public goods, but also more on public goods from which individuals benefit equally rather than unequally. We examine this possibility by comparing ideologically left-leaning and right-leaning individuals’ cooperation on multiple public goods that varied in efficiency and (in)equality in returns. We find that left-leaning individuals cooperate more than right-leaning ones, but only on public goods that benefit everyone equally, and not more on public goods that generate inequalities. Left-leaning individuals also trust and expect others to cooperate more on equal- versus unequal-returns public goods, while self-identified right-leaning individuals do not differentiate between these. Interestingly, ideology does not predict which public good is deemed more morally appropriate to cooperate on. Results combined specify when and why self-identified leftists can(not) be expected to cooperate more than rightists and reveal how moral decision-making depends on structural elements of the public good provision problems that citizens face.
Fine-grained multi-focus image fusion based on edge features
Authors: Tian Bin , Yang Lichun , Dang Jianwu
Published: February 2023

Multi-focus image fusion is a process of fusing multiple images of different focus areas into a total focus image, which has important application value. In view of the defects of the current fusion method in the detail information retention effect of the original image, a fusion architecture based on two stages is designed. In the training phase, combined with the polarized self-attention module and the DenseNet network structure, an encoder-decoder structure network is designed for image reconstruction tasks to enhance the original information retention ability of the model. In the fusion stage, combined with the encoded feature map, a fusion strategy based on edge feature map is designed for image fusion tasks to enhance the attention ability of detail information in the fusion process. Compared with 9 classical fusion algorithms, the proposed algorithm has achieved advanced fusion performance in both subjective and objective evaluations, and the fused image has better information retention effect on the original image.
Meta-analysis of NAD(P)(H) quantification results exhibits variability across mammalian tissues
Authors: Azouaoui Dassine , Choinière Michael René , Khan Momtafin , Sayfi Shahab , Jaffer Simran , Yousef Selvia , Patten David A. , Green Alexander E. , Menzies Keir J.
Published: February 2023

Nicotinamide Adenine Dinucleotide (NAD+) plays an important role in energy metabolism and signaling pathways controlling crucial cellular functions. The increased interest in NAD+ metabolism and NAD+-boosting therapies has reinforced the necessity for accurate NAD+ quantification. To examine the published NAD(P)(H) measures across mammalian tissues, we performed a meta-analysis of the existing data. An Ovid MEDLINE database search identified articles with NAD(P)(H) quantification results obtained from mammalian tissues published between 1961 and 2021. We screened 4890 records and extracted quantitative data, as well as the quantification methods, pre-analytical conditions, and subject characteristics. The extracted physiological NAD(P)(H) concentrations in various tissues from mice, rats, and humans, revealed an important inter- and intra-method variability that extended to recent publications. This highlights the relatively poor potential for cross-experimental analyses for NAD(P)(H) quantitative data and the importance of standardization for NAD(P)(H) quantification methods and pre-analytical procedures for future preclinical and clinical studies.
DeepInsight-3D architecture for anti-cancer drug response prediction with deep-learning on multi-omics
Authors: Sharma Alok , Lysenko Artem , Boroevich Keith A. , Tsunoda Tatsuhiko
Published: February 2023

Modern oncology offers a wide range of treatments and therefore choosing the best option for particular patient is very important for optimal outcome. Multi-omics profiling in combination with AI-based predictive models have great potential for streamlining these treatment decisions. However, these encouraging developments continue to be hampered by very high dimensionality of the datasets in combination with insufficiently large numbers of annotated samples. Here we proposed a novel deep learning-based method to predict patient-specific anticancer drug response from three types of multi-omics data. The proposed DeepInsight-3D approach relies on structured data-to-image conversion that then allows use of convolutional neural networks, which are particularly robust to high dimensionality of the inputs while retaining capabilities to model highly complex relationships between variables. Of particular note, we demonstrate that in this formalism additional channels of an image can be effectively used to accommodate data from different omics layers while implicitly encoding the connection between them. DeepInsight-3D was able to outperform other state-of-the-art methods applied to this task. The proposed improvements can facilitate the development of better personalized treatment strategies for different cancers in the future.
Gut microbiome composition associates with corticosteroid treatment, morbidity, and senescence in Chinook salmon (Oncorhynchus tshawytscha)
Authors: Couch Claire E. , Neal William T. , Herron Crystal L. , Kent Michael L. , Schreck Carl B. , Peterson James T.
Published: February 2023

Pacific salmon experience prolonged elevation in corticosteroid hormones during important life history events including migration, reproduction, and senescence. These periods of elevated corticosteroids correspond with changes to immunity and energy metabolism; therefore, fish may be particularly vulnerable to mortality at these times. Recent studies found that stress-induced cortisol release associated with microbial community shifts in salmonids, raising the question of how longer-term corticosteroid dynamics that accompany life history transitions affect salmonid microbiomes. In this work, we experimentally evaluated the relationships between gut microbiome composition, chronically elevated corticosteroids, and mortality in juvenile Chinook salmon (Oncorhynchus tshawytscha). We found that treatment with slow-release implants of the corticosteroids cortisol or dexamethasone resulted in changes to the gut microbiome. Morbidity was also associated with microbiome composition, suggesting that the gut microbiome reflects individual differences in susceptibility to opportunistic pathogens. Additionally, we analyzed a small number of samples from adult fish at various stages of senescence. Results from these samples suggest that microbiome composition associated with gut integrity, and that the microbial communities of corticosteroid treated juveniles shift in composition toward those of senescent adults. Overall, findings from this work indicate that the gut microbiome correlates with mortality risk during periods of chronic corticosteroid elevation.
Bioinformatics construction and experimental validation of a cuproptosis-related lncRNA prognostic model in lung adenocarcinoma for immunotherapy response prediction
Authors: Li Linfeng , Cai Qidong , Wu Zeyu , Li Xizhe , Zhou Wolong , Lu Liqing , Yi Bin , Chang Ruimin , Zhang Heng , Cheng Yuanda , Zhang Chunfang , Zhang Junjie
Published: February 2023

Cuproptosis is a newly form of cell death. Cuproptosis related lncRNA in lung adenocarcinoma (LUAD) has also not been fully elucidated. In the present study, we aimed to construct a prognostic signature based on cuproptosis-related lncRNA in LUAD and investigate its association with immunotherapy response. The RNA-sequencing data, clinical information and simple nucleotide variation of LUAD patients were obtained from TCGA database. The LASSO Cox regression was used to construct a prognostic signature. The CIBERSORT, ESTIMATE and ssGSEA algorithms were applied to assess the association between risk score and TME. TIDE score was applied to reflect the efficiency of immunotherapy response. The influence of overexpression of lncRNA TMPO-AS1 on A549 cell was also assessed by in vitro experiments. The lncRNA prognostic signature included AL606834.1, AL138778.1, AP000302.1, AC007384.1, AL161431.1, TMPO-AS1 and KIAA1671-AS1. Low-risk group exhibited much higher immune score, stromal score and ESTIMATE score, but lower tumor purity compared with high-risk groups. Also, low-risk group was associated with a much higher score of immune cells and immune related function sets, indicating an immune activation state. Low-risk patients had relative higher TIDE score and lower TMB. External validation using IMvigor210 immunotherapy cohort demonstrated that low-risk group had a better prognosis and might more easily benefit from immunotherapy. Overexpression of lncRNA TMPO-AS1 promoted the proliferation, migration and invasion of A549 cell line. The novel cuproptosis-related lncRNA signature could predict the prognosis of LUAD patients, and helped clinicians stratify patients appropriate for immunotherapy and determine individual therapeutic strategies.
Development and application of a new biological nano-selenium fermentation broth based on Bacillus subtilis SE201412
Authors: Huang Sisi , Yu Kan , Wen Liang , Long Xiaoling , Sun Jin , Liu Quxiao , Zheng Zhuo , Zheng Wei , Luo Hongmei , Liu Jinlong
Published: February 2023

In order to improve the functionality and additional value of agricultural products, this study developing nano-selenium fermentation broth and established a new application strategy of bio-nano-selenium by screening and identifying selenium-rich microorganisms. We isolated a new strain from tobacco waste and named it Bacillus subtilis SE201412 (GenBank accession no. OP854680), which could aerobically grow under the condition of 66,000 mg L−1 selenite concentration, and could convert 99.19% of selenite into biological nano-selenium (BioSeNPs) within 18 h. Using strain SE201412, we industrially produced the different concentrations of fermentation broth containing 5000–3000 mg L−1 pure selenium for commercial use. The synthesized selenium nanoparticles (SeNPs) were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). TEM and SEM results showed that SeNPs were distributed outside cells. NTA assay of fermentation broth indicated that the nanoparticles were spherical with an average particle size of 126 ± 0.5 nm. Toxicity test revealed that the median lethal dose (LD50) of the fermentation broth to mice was 2710 mg kg−1, indicating its low toxicity and high safety. In addition, we applied BioSeNP fermentation broth to rice and wheat through field experiments. The results showed that the application of fermentation broth significantly increased the total selenium content and organic selenium percentage in rice and wheat grains. Our findings provide valuable reference for the development of BioSeNPs with extensive application prospects.
Reversal of aging-associated increase in myelopoiesis and expression of alarmins by angiotensin-(1–7)
Authors: Chittimalli Kishore , Jahan Jesmin , Sakamuri Anil , Weyrick Hope , Winkle Wink , Adkins Steven , Vetter Stefan W. , Jarajapu Yagna P. R.
Published: February 2023

Aging is associated with chronic systemic inflammation largely due to increased myelopoiesis, which in turn increases risk for vascular disease. We have previously shown evidence for the therapeutic potential of Angiotensin-(1–7) (Ang-(1–7)) in reversing vasoreparative dysfunction in aging. This study tested the hypothesis that ischemic vascular repair in aging by Ang-(1–7) involves attenuation of myelopoietic potential in the bone marrow and decreased mobilization of inflammatory cells. Young or Old male mice of age 3–4 and 22–24 months, respectively, received Ang-(1–7) (1 µg/kg/min, s.c.) for four weeks. Myelopoiesis was evaluated in the bone marrow (BM) cells by carrying out the colony forming unit (CFU-GM) assay followed by flow cytometry of monocyte-macrophages. Expression of pro-myelopoietic factors and alarmins in the hematopoietic progenitor-enriched BM cells was evaluated. Hindlimb ischemia (HLI) was induced by femoral ligation, and mobilization of monocytes into the blood stream was determined. Blood flow recovery was monitored by Laser Doppler imaging and infiltration of inflammatory cells was evaluated by immunohistochemistry. BM cells from Old mice generated a higher number of monocytes (Ly6G-CD11b+Ly6Chi) and M1 macrophages (Ly6ChiF4/80+) compared to that of Young, which was reversed by Ang-(1–7). Gene expression of selected myelopoietic factors, alarmins (S100A8, S100A9, S100A14 and HMGb1) and the receptor for alarmins, RAGE, was higher in the Old hematopoietic progenitor-enriched BM cells compared to the Young. Increased expressions of these factors were decreased by Ang-(1–7). Ischemia-induced mobilization of monocytes was higher in Old mice with decreased blood flow recovery and increased infiltration of monocyte-macrophages compared to the Young, all of which were reversed by Ang-(1–7). Enhanced ischemic vascular repair by Ang-(1–7) in aging is largely by decreasing the generation and recruitment of inflammatory monocyte-macrophages to the areas of ischemic injury. This is associated with decreased alarmin signaling in the BM-hematopoietic progenitor cells.
Effects of percutaneous transluminal angioplasty and associated factors in access hand oxygenation in patients undergoing hemodialysis
Authors: Sugiyama Tomoko , Ito Kiyonori , Ookawara Susumu , Shimoyama Hirofumi , Shindo Mitsutoshi , Hirata Momoko , Shimoyama Hiromi , Nakazato Yuichi , Morishita Yoshiyuki
Published: February 2023

In hemodialysis (HD) patients with arteriovenous fistula (AVF), changes in systemic or peripheral tissue circulation occur non-physiologically via the presence of AVF; however, associations between blood flow and tissue oxygenation in the brain and access hand are uncertain. In this study, 85 HD patients with AVF were included and evaluated for changes in flow volume (FV) and regional oxygen saturation (rSO2) in the brain and hands with AVF before and after percutaneous transluminal angioplasty (PTA). Furthermore, we evaluated the factors that determine access hand rSO2 without stenosis after PTA. Brachial arterial FV increased after PTA (p < 0.001), and carotid FV decreased (p = 0.008). Access hand rSO2 significantly decreased after PTA (p < 0.001), but cerebral rSO2 did not significantly change (p = 0.317). In multivariable linear regression analysis of factors associated with access hand rSO2, serum creatinine (standardized coefficient: 0.296) and hemoglobin (standardized coefficient: 0.249) were extracted as independent factors for access hand rSO2. In conclusion, a decrease in access hand oxygenation and maintenance of cerebral oxygenation were observed throughout PTA. To maintain access hand oxygenation, it is important to adequately manage Hb level and maintain muscle mass, in addition to having an AVF with appropriate blood flow.
Evolving scattering networks for engineering disorder
Authors: Yu Sunkyu
Published: February 2023

Network science provides a powerful tool for unraveling the complexities of social, technological and biological systems. Constructing networks using wave phenomena is also of great interest in devising advanced hardware for machine learning, as shown in optical neural networks. Although most wave-based networks have employed static network models, the impact of evolving models in network science provides strong motivation to apply dynamical network modeling to wave physics. Here the concept of evolving scattering networks for scattering phenomena is developed. The network is defined by links, node degrees and their evolution processes modeling multi-particle interferences, which directly determine scattering from disordered materials. I demonstrate the concept by examining network-based material classification, microstructure screening and preferential attachment in evolutions, which are applied to stealthy hyperuniformity. The results enable independent control of scattering from different length scales, revealing superdense material phases in short-range order. The proposed concept provides a bridge between wave physics and network science to resolve multiscale material complexities and open-system material design.