Phase-Pure α-Sn Quantum Material on Si Seeded by a 2 nm-Thick Ge Layer.

α-Sn, a new elemental topological quantum material, has drawn substantial attention lately. Unique transport properties and intriguing spintronics applications of α-Sn are demonstrated, resurrecting this material from its notorious "tin pest" infamy. With a diamond cubic crystal structure, group-IV α-Sn holds the potential for integrated topological quantum devices on Si. However, directly growing α-Sn on Si is still challenging due to the ≈20% lattice mismatch. Here, a new method is demonstrated to grow 200 nm-thick α-Sn microstructures on a 2 nm-thick Ge seed layer on Si substrate by physical vapor deposition. In situ Raman spectroscopy reveals that the as-deposited ß-Sn melts upon rapid thermal annealing at 350-450 °C and solidifies to α-Sn after cooling back to room temperature, seeded by heterogeneous nucleation on the Ge layer. Cooling condition and HCl etching are tuned to achieve phase-pure α-Sn microstructures toward quantum devices. Approximately 1 at.% Ge is alloyed into α-Sn due to diffusion from the Ge seed layer, which helps stabilize α-Sn thermodynamically to facilitate device processing. A compressive strain is incorporated into these α-Sn microstructures, making them 3D topological Dirac semimetals for integrated quantum devices on Si.

Understanding the cognitive and neuroimaging bases underlying the detrimental impact of sleep deprivation on reciprocity.

Although the impact of sleep loss on social behaviors has been widely observed in recent years, the mechanisms underpinning these impacts remain unclear. In this study, we explored the detrimental effects of sleep deprivation on reciprocity behavior as well as its underlying psychological and neuroimaging mechanisms by combining sleep manipulation, an interpersonal interactive game, computational modeling and neuroimaging. Our results suggested that after sleep deprivation, individuals showed reduced reciprocity behavior, mainly due to their reduced weights on communal concern when making social decisions. At neural level, we demonstrated that sleep deprivation's effects were observed in the precuneus (hyperactivity) and temporoparietal junction, dorsal lateral prefrontal cortex (DLPFC) (both hypoactivity), and reduced reciprocity was also accounted for by increased precuneus-thalamus connectivity and DLPFC-thalamus connectivity. Our findings contributed to the understanding of the psychological and neuroimaging bases underlying the deleterious impact of sleep deprivation on social behaviors.

The psychological, computational, and neural foundations of indebtedness.

Receiving a favor from another person may induce a negative feeling of indebtedness for the beneficiary. In this study, we explore these hidden costs by developing and validating a conceptual model of indebtedness across three studies that combine a large-scale online questionnaire, an interpersonal game, computational modeling, and neuroimaging. Our model captures how individuals perceive the altruistic and strategic intentions of the benefactor. These inferences produce distinct feelings of guilt and obligation that together comprise indebtedness and motivate reciprocity. Perceived altruistic intentions convey care and communal concern and are associated with activity in insula, ventromedial prefrontal cortex and dorsolateral prefrontal cortex, while inferred strategic intentions convey expectations of future reciprocity and are associated with activation in temporal parietal junction and dorsomedial prefrontal cortex. We further develop a neural utility model of indebtedness using multivariate patterns of brain activity that captures the tradeoff between these feelings and reliably predicts reciprocity behavior.

Calycosin inhibits hepatocyte apoptosis in acute liver failure by suppressing the TLR4/NF-κB pathway: An in vitro study.

BACKGROUND: Acute liver failure (ALF) is a serious liver disease that is difficult to treat owing to its unclear pathogenesis. This study aimed to investigate the roles and molecular mechanisms of calycosin (CA) in ALF. METHODS: In this study, the roles and mechanism of CA in ALF were explored using an in vitro lipopolysaccharide (LPS)-induced ALF cell model. Additionally, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide assay was used to assess the effect of CA on the activity of LPS-induced L02 human liver epithelial cells, and flow cytometry was used to detect apoptosis in L02 cells. Expression levels of apoptosis-related genes, Bax and Bcl-2, were measured using reverse transcription-quantitative polymerase chain reaction and Western blot analysis. Expression levels of inflammatory factors in LPS-induced L02 cells were measured using an enzyme-linked immunosorbent assay. Additionally, the effect of CA on ALF was inhibited via transfection of a toll-like receptor 4 (TLR4)-plasmid to elucidate the relationship between CA and TLR4/nuclear factor (NF)-κB signaling pathway in ALF. RESULTS: CA had no toxic effects on L02 cells, but enhanced the activity of LPS-induced L02 cells in a dose-dependent manner. Apoptosis and inflammatory factor release was increased in ALF, activating the TLR4/NF-κB signaling pathway. However, CA treatment inhibited the apoptosis and release of inflammatory factors. Further mechanistic studies revealed that the upregulation of TLR4 expression reversed the alleviating effects of CA on inflammation and apoptosis in LPS-induced L02 cells. CONCLUSION: CA alleviates inflammatory damage in LPS-induced L02 cells by inhibiting the TLR4/NF-κB pathway and may be a promising therapeutic agent for ALF treatment.

Synergistic Photon Management and Strain-Induced Band Gap Engineering of Two-Dimensional MoS2 Using Semimetal Composite Nanostructures.

2D MoS2 attracts increasing attention for its application in flexible electronics and photonic devices. For 2D material optoelectronic devices, the light absorption of the molecularly thin 2D absorber would be one of the key limiting factors in device efficiency, and conventional photon management techniques are not necessarily compatible with them. In this study, we show two semimetal composite nanostructures deposited on 2D MoS2 for synergistic photon management and strain-induced band gap engineering: (1) the pseudo-periodic Sn nanodots, (2) the conductive SnOx (x < 1) core-shell nanoneedle structures. Without sophisticated nanolithography, both nanostructures are self-assembled from physical vapor deposition. Optical absorption enhancement spans from the visible to the near-infrared regime. 2D MoS2 achieves >8× optical absorption enhancement at λ = 700-940 nm and 3-4× at λ = 500-660 nm under Sn nanodots, and 20-30× at λ = 700-900 nm under SnOx (x < 1) nanoneedles. The enhanced absorption in MoS2 results from strong near-field enhancement and reduced MoS2 band gap due to the tensile strain induced by the Sn nanostructures, as confirmed by Raman and photoluminescence spectroscopy. Especially, we demonstrate that up to 3.5% biaxial tensile strain is introduced to 2D MoS2 using conductive nanoneedle-structured SnOx (x < 1), which reduces the band gap by ∼0.35 eV to further enhance light absorption at longer wavelengths. To the best of our knowledge, this is the first demonstration of a synergistic triple-functional photon management, stressor, and conductive electrode layer on 2D MoS2. Such synergistic photon management and band gap engineering approach for extended spectral response can be further applied to other 2D materials for future 2D photonic devices.

The single- and dual-brain mechanisms underlying the adviser's confidence expression strategy switching during influence management.

Effective influence management during advice-giving requires individuals to express confidence in the advice properly and switch timely between the 'competitive' strategy and the 'defensive' strategy. However, how advisers switch between these two strategies, and whether and why there exist individual differences during this process remain elusive. We used an advice-giving game that manipulated incentive contexts (Incentivized/Non-Incentivized) to induce the adviser's confidence expression strategy switching and measured the brain activities of adviser and advisee concurrently using functional near-infrared spectroscopy (fNIRS). Behaviorally, we observed individual differences in strategy switching. Some advisers applied the 'defensive' strategy when incentivized and the 'competitive' strategy when not incentivized, while others applied the 'competitive' strategy when incentivized and the 'defensive' strategy when not incentivized. This effect was mediated by the adviser's perceived stress in each condition and was reflected by the frequencies of advice-taking in the advisees. Neurally, brain activation in the dorsolateral prefrontal cortex (DLPFC) supported strategy switching, as well as interpersonal neural synchronization (INS) in the temporoparietal junction (TPJ) that supported influence management. This two-in-one process, i.e., confidence expression strategy switching and the corresponding influence management, was linked and modulated by the strength of DLPFC-TPJ functional connectivity in the adviser. We further developed a descriptive model that contributed to understanding the adviser's strategy switching during influence management.

Understanding guilt-related interpersonal dysfunction in obsessive-compulsive personality disorder through computational modeling of two social interaction tasks.

BACKGROUND: Obsessive-compulsive personality disorder (OCPD) is a high-prevalence personality disorder characterized by subtle but stable interpersonal dysfunction. There have been only limited studies addressing the behavioral patterns and cognitive features of OCPD in interpersonal contexts. The purpose of this study was to investigate how behaviors differ between OCPD individuals and healthy controls (HCs) in the context of guilt-related interpersonal responses. METHOD: A total of 113 participants were recruited, including 46 who were identified as having OCPD and 67 HCs. Guilt-related interpersonal responses were manipulated and measured with two social interactive tasks: the Guilt Aversion Task, to assess how anticipatory guilt motivates cooperation; and the Guilt Compensation Task, to assess how experienced guilt induces compensation behaviors. The guilt aversion model and Fehr-Schmidt inequity aversion model were adopted to analyze decision-making in the Guilt Aversion Task and the Guilt Compensation Task, respectively. RESULTS: Computational model-based results demonstrated that, compared with HCs, the OCPD group exhibited less guilt aversion when making cooperative decisions as well as less guilt-induced compensation after harming others. CONCLUSION: Our findings indicate that individuals with OCPD tend to be less affected by guilt than HCs. These impairments in guilt-related responses may prevent adjustments in behaviors toward compliance with social norms and thus result in interpersonal dysfunctions.

Understanding an implicated causality: The brain network for processing concessive relations.

Concessive relations, often indicated by conjunction words such as although, are semantically and pragmatically more complex than causal relations (expressed using because), as they involve more semantic features such as implicated meaning and negation. However, it remains unclear how linguistic-level complexity is manifested through different brain activities and functional connectivities. This fMRI study investigated how the neural underpinnings of concessive relations differ from those of causal relations. Pragmatically congruent and incongruent words were embedded in causal as well as concessive sentences. The whole-brain analysis revealed that relative to because-congruent sentences, although-congruent sentences evoked increased activations in a left network including IFG, bilateral MFG, mPFC, pMTG, and TPJ. DCM analysis showed that while the functional connectivity from IFG to MFG was commonly involved in processing concessive and causal relations, functional connectivities from pMTG to IFG and from pMTG to TPJ were involved in processing causal and concessive relations, respectively.

Neural mechanisms of the mood effects on third-party responses to injustice after unfair experiences.

Behavioral decision theory argues that humans can adjust their third-party responses (e.g., punishment and compensation) to injustice by integrating unfair experiences. Typically, the mood plays an important role in such a decision-making process. However, the underlying neurocognitive bases remain largely unclear. We first employ a modified third-party justice game in which an allocator split an amount of money between oneself and a receiver. The participants can reapportion the money as observers by choosing from the following three costly options: compensate the receiver, accept the current allocation, or punish the allocator. Then, a second-party pseudo interaction is conducted where participants receive more (i.e., advantageous unfair experience) or less (i.e., disadvantageous unfair experience) than others. Finally, participants perform the third-party justice game again after unfair experiences. Here, we use functional near-infrared spectroscopy (fNIRS) to measure participants' brain activities during third-party responses to injustice. We find participants compensate more to the receiver after advantageous unfair experience, which involved enhanced positive emotion, weakened sense of unfairness, and is linked with increased activity in the right dorsolateral prefrontal cortex (rDLPFC). In contrast, participants punish more on the allocator after disadvantageous unfair experience, which might primarily stem from their negative emotional responses, strong sense of unfairness, and is associated with significantly decreased activity in the rDLPFC. Our results suggest that third-party compensation and punishment involved differential psychological and neural bases. Our findings highlight the crucial roles of second-party unfair experiences and the corresponding mood responses in third-party responses to unfairness, and unravel the intermediate neural architecture.

Oceanospirillum sediminis sp. nov., Isolated From Coastal Sediment in the Yellow Sea.

A novel Gram-negative, motile, aerobic, spiral-shaped bacterium designated D5T, was isolated from a coastal sediment collected in the Yellow Sea. Optimal growth occurred at 30 °C, pH 7.0-8.0 and in the presence of 1-3% (w/v) NaCl. Strain D5T contained ubiquinone 8 (Q-8) as the predominant respiratory quinone. The major fatty acids (> 10%) were C16:0, C16:1 ω7c/C16:1 ω6c and C18:1w7c/C18:1w6c. The main polar lipids were phosphatidylglycerol and phosphatidylethanolamine. The draft genome is 5.6 Mb in length, and DNA G + C content is 47.2 mol%. 16S rRNA gene sequences showed that strain D5T is most closely related to Oceanospirillum beijerinckii NBRC 15445T (97.8%, sequence similarity). However, the digital DNA-DNA hybridization (dDDH) value and average nucleotide identity (ANI) between strain D5T and O. beijerinckii is only 27.8% and 77.1%. Phylogenetic trees based on 16S rRNA gene sequences and whole genomes all indicated that strain D5T formed a separate branch in the genus Oceanospirillum. Combined results of the polyphasic analyses suggested that strain D5T represents a novel species in the genus Oceanospirillum, for which the name Oceanospirillum sediminis sp. nov. is proposed. The type strain is D5T (= MCCC 1K06061T = KCTC 62987T).

Benefits from Shortening Viral Shedding by Traditional Chinese Medicine Treatment for Moderate COVID-19: An Observational Study.

Traditional Chinese medicine (TCM) treatment for the coronavirus disease 2019 (COVID-19) can improve clinical symptoms, but it is not clear whether it can shorten viral shedding. This is an observational study including 97 patients with COVID-19 who were consecutively admitted to the Jiangxia Fangcang hospital in Wuhan (Hubei, China) from January 15, 2020, to March 10, 2020. All patients were treated with TCM, and we assessed the patients daily and collected clinical information via a diary card. The primary endpoint was the time to achieve a negative result for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) RT-PCR. The final analysis included 92 patients. The median time to negative oropharyngeal swab for all the participants was 22 days (IQR 15-30). The participants were divided into three groups according to time from symptom onset to start of TCM treatment: within 7 days group (early treatment group), 8-14 days group (middle treatment group), and over 14 days group (late treatment group). The median time to negative oropharyngeal swab for the early treatment group was 14 days (IQR 12-17) and for the middle and late treatment groups was statistically shorter than 20 days (IQR 18-22) and 30 days (IQR 25-34), respectively. In univariate Cox proportional hazards regression analysis, the incidence of negative oropharyngeal swab for the early and middle treatment groups was 7.674 times and 3.609 times statistically higher than the late treatment group, respectively; whereas in multivariate Cox proportional hazards regression analysis, the incidence for the early and middle treatment groups was 18.093 times and 5.804 times statistically higher than the late treatment group, respectively. In patients with moderate COVID-19, those who had no cough, no dyspnea, and those who received TCM treatment earlier could achieve nucleic acid negative sooner by shortening viral shedding.

The mutuality of social emotions: How the victim's reactive attitude influences the transgressor's emotional responses.

Would a transgressor be guiltier or less after receiving the victim's forgiving or blaming attitude? Everyday intuitions and empirical evidence are mixed in this regard, leaving how interpersonal attitudes shape the transgressor's reactive social emotions an open question. We combined a social interactive game with multivariate pattern analysis of fMRI data to address this question. Participants played an interactive game in an fMRI scanner where their incorrect responses could cause either high or low pain stimulation to an anonymous co-player. Following incorrect responses, participants were presented with the co-player's (i.e., the victim's) attitude towards the harm (Blame, Forgive, or Neutral). Behaviorally, the victim's attitude and the severity of harm interactively modulated the transgressor's social emotions, with expectation violation serving as a mediator. While unexpected forgiveness following severe harm amplified the participants' guilt, unexpected blame following minor harm reduced the participants' guilt and increased their anger. This role of expectation violation was supported by multivariate pattern analysis of fMRI, revealing a shared neural representation in ventral striatum in the processing of victim's attitude-induced guilt and anger. Moreover, we identified a neural re-appraisal process of guilt in the transgressor, with the involvement of area related to self-conscious processing (i.e., perigenual anterior cingulate cortex) before knowing the victim's attitude transiting to the involvement of other-regarding related area (i.e., temporoparietal junction) after knowing the victim's attitude. These findings uncover the neurocognitive bases underlying the transgressor's social emotional responses, and highlight the importance of the mutuality of social emotions.

Testosterone reduces generosity through cortical and subcortical mechanisms.

Recent evidence has linked testosterone, a major sex hormone, to selfishness in economic decision-making. Here, we aimed to investigate the neural mechanisms through which testosterone reduces generosity by combining functional MRI with pharmacological manipulation among healthy young males in a double-blind, placebo-controlled, between-subject design. After testosterone or placebo gel administration, participants performed a social discounting task in which they chose between selfish options (benefiting only the participant) and generous options (providing also some benefit to another person at a particular social distance). At the behavioral level, testosterone reduced generosity compared to the placebo. At the neural level (n = 60), the temporoparietal junction (TPJ) encoded the other-regarding value of the generous option during generous choices, and this effect was attenuated by testosterone, suggesting that testosterone reduced the consideration of other's welfare as underpinned by TPJ activity. Moreover, TPJ activity more strongly reflected individual differences in generosity in the placebo than the testosterone group. Furthermore, testosterone weakened the relation between the other-regarding value of generous decisions and connectivity between the TPJ and a region extending from the insula into the striatum. Together, these findings suggest that a network encompassing both cortical and subcortical components underpins the effects of testosterone on social preferences.

Anti-perimenopausal osteoporosis effects of Erzhi formula via regulation of bone resorption through osteoclast differentiation: A network pharmacology-integrated experimental study.

ETHNOPHARMACOLOGICAL RELEVANCE: Erzhi formula (EZF) consists of Ecliptae herba (EH) and Fructus Ligustri Lucidi (FLL) at a ratio 1:1, and constitutes a well-known formula in China that is commonly used for treating menopausal diseases. AIM OF THE STUDY: In this study, we explored the pharmacologic actions and potential molecular mechanisms underlying EZF's action in preventing and treating osteoporosis. MATERIALS AND METHODS: The active components and related targets of EZF's anti-osteoporotic effects were predicted by network pharmacology, and functional enrichment analysis was also performed. We then used an osteoporosis model of ovariectomized (OVX) mice to detect the effects of EZF on osteoporosis. RESULTS: The results from network pharmacology identified a total of 10 active ingredients from EH and 13 active ingredients from FLL that might affect 65 potential therapeutic targets. GO enrichment analysis revealed that EZF affected bone tissue primarily via hormone (particularly estradiol)-related pathways and bone resorption by osteoclast differentiation. KEGG analysis demonstrated that bone-related factors such as Runt-related transcription factor 2 (Runx2), Ca2, estrogen receptor1 (ESR1), androgen receptors (AR), and TNFα served as the primary targets during osteoclastic differentiation. In vivo experiments showed that the formula significantly improved the diminution in estrogen and the subsequent uterine atrophy induced by ovariectomy (P < 0.01 or 0.05), implying that the EZF exerted its actions via regulation of estradiol and the nourishing effects of the uterus in OVX mice. Dual-energy X-ray absorptiometry and micro-CT showed that EZF significantly inhibited bone loss and improved bone micro-architecture by statistically increasing the number of bone trabeculae and decreasing the separation of bone trabeculae in OVX mice (P < 0.01 or 0.05); EZF also inhibited bone loss and enhanced bone-fracture load. Furthermore, we confirmed that EZF reduced the calcium concentrations, augmented protein and mRNA levels for Runx2 in the bone marrow, and reduced PPARγ levels. RANKL-a key downstream regulatory protein of many targets that was referred to in our results of network pharmacology as being involved in the regulation of osteoclastogenesis-was significantly diminished by EZF; it also elevated OPG content. In addition, we used monocytes of bone-marrow origin to detect the effects of the potential components of EZF on osteoclast differentiation and found that wedelolactone, oleanolic acid, echinocystic acid, luteolin, and luteolin-7-o-glucoside significantly inhibited osteoclast differentiation from monocytes induced by 25 ng/mL MCSF and 50 ng/mL RANKL (P < 0.01 or 0.05). CONCLUSIONS: Our present study indicated that EZF significantly inhibited the bone loss induced by OVX in mice by its regulation of estradiol combined with the nourishing effect of the uterus, and that it also attenuated bone resorption by decreasing the RANKL/OPG ratio so as to inhibit osteoclast maturation.

Bach2 Deficiency Promotes Intestinal Epithelial Regeneration by Accelerating DNA Repair in Intestinal Stem Cells.

Epithelial regeneration is critical for barrier maintenance and organ function after intestinal injury, although the repair mechanisms are unclear. Here, we found that Bach2 deficiency promotes intestinal epithelial cell proliferation during homeostasis. Moreover, genetic inactivation of Bach2 in mouse intestinal epithelium facilitated crypt regeneration after irradiation, resulting in a reduction in mortality. RNA-sequencing analysis of isolated crypts revealed that Bach2 deficiency altered the expression of numerous genes, including those regulating double-strand break repair. Mechanistic characterizations indicated that Bach2 deletion facilitated DNA repair in intestinal crypt cells, as evidenced by faster resolution of γ-H2AX and 53BP1 foci in Bach2-/- crypt cells, compared with Bach2+/+ control. Together, our studies highlight that Bach2 deficiency promotes intestinal regeneration by accelerating DNA repair in intestinal stem cells after radiation damage.

Right Temporoparietal Junction Underlies Avoidance of Moral Transgression in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is characterized by a core difference in theory-of-mind (ToM) ability, which extends to alterations in moral judgment and decision-making. Although the function of the right temporoparietal junction (rTPJ), a key neural marker of ToM and morality, is known to be atypical in autistic individuals, the neurocomputational mechanisms underlying its specific changes in moral decision-making remain unclear. Here, we addressed this question by using a novel fMRI task together with computational modeling and representational similarity analysis (RSA). ASD participants and healthy control subjects (HCs) decided in public or private whether to incur a personal cost for funding a morally good cause (Good Context) or receive a personal gain for benefiting a morally bad cause (Bad Context). Compared with HC, individuals with ASD were much more likely to reject the opportunity to earn ill gotten money by supporting a bad cause than were HCs. Computational modeling revealed that this resulted from heavily weighing benefits for themselves and the bad cause, suggesting that ASD participants apply a rule of refusing to serve a bad cause because they evaluate the negative consequences of their actions more severely. Moreover, RSA revealed a reduced rTPJ representation of the information specific to moral contexts in ASD participants. Together, these findings indicate the contribution of rTPJ in representing information concerning moral rules and provide new insights for the neurobiological basis underpinning moral behaviors illustrated by a specific difference of rTPJ in ASD participants.SIGNIFICANCE STATEMENT Previous investigations have found an altered pattern of moral behaviors in individuals with autism spectrum disorder (ASD), which is closely associated with functional changes in the right temporoparietal junction (rTPJ). However, the specific neurocomputational mechanisms at play that drive the altered function of the rTPJ in moral decision-making remain unclear. Here, we show that ASD individuals are more inflexible when following a moral rule although an immoral action can benefit themselves, and experience an increased concern about their ill-gotten gains and the moral cost. Moreover, a selectively reduced rTPJ representation of information concerning moral rules was observed in ASD participants. These findings deepen our understanding of the neurobiological roots that underlie atypical moral behaviors in ASD individuals.

Organoid modelling identifies that DACH1 functions as a tumour promoter in colorectal cancer by modulating BMP signalling.

BACKGROUND: Dachshund homologue 1 (DACH1) is highly expressed in LGR5+ intestinal stem cells and colorectal tumours. However, the roles of DACH1 in intestinal cell stemness and colorectal tumorigenesis remain largely undefined. METHODS: We used immunohistochemistry, western blotting and quantitative real-time PCR to analyse DACH1 expression in colorectal cancer (CRC) samples. CRISPR/Cas9 gene editing and lentiviral vector-mediated overexpression and shRNA-mediated knockdown of DACH1 were utilized to modulate DACH1 expression in cell lines and organoids. An intestinal organoid-based functional model was analysed, and cancer cell colony formation, sphere formation assays and murine xenotransplants were performed to reveal the role of DACH1 in CRC cell proliferation, stemness and tumorigenesis. Immunofluorescence, co-immunoprecipitation, RNA interference and microarray data analyses were conducted to demonstrate the association between DACH1 and the bone morphogenetic protein (BMP) signalling pathway. FINDINGS: DACH1 is specifically expressed in discrete crypt base cells, and increased DACH1 expression was found in all stages of CRC. Moreover, the high expression of DACH1 independently predicted poor prognosis. In colon cancer cells, shRNA-mediated suppression of DACH1 inhibited cell growth in vitro and in vivo. By studying the intestinal organoid-based functional model, we found that depletion of DACH1 reduced the organoid formation efficiency and tumour organoid size. DACH1 overexpression stimulated both colonsphere formation and tumour organoid formation in the context of dysregulated BMP signalling. Mechanistic characterizations indicated that overexpression of DACH1 affects a subset of stem cell signature genes implicated in stem cell proliferation and maintenance through the suppression of BMP signalling via SMAD4. INTERPRETATION: Together, our study highlights DACH1 as an integral regulator of BMP signalling during intestinal tumorigenesis, and DACH1 could be a potential prognostic marker and therapeutic target for colorectal cancer patients.

Affective evaluation of others' altruistic decisions under risk and ambiguity.

Gratitude arises when one is the target of an altruistic decision, particularly when this decision incurs cost to the agent. Here we examined how individuals evaluate others' altruistic decisions under risky (uncertainty with known probabilities) and ambiguous (uncertainty with unknown probabilities) costs and respond with gratitude and reciprocity. Participants played an interactive game in an fMRI scanner in which they would receive painful electric shocks. An anonymous co-player either intentionally (Human conditions) or unintentionally (Computer conditions) decided whether to help the participant reduce half of the pain by undertaking an amount of pain (i.e., cost) with varying level of uncertainty (Certain vs. Risky vs. Ambiguous). Participants could then transfer monetary points to the co-player knowing that the co-player was unaware of this transfer. Behaviorally, monetary allocation and gratitude rating increased as the uncertainty level of cost increased in Human conditions; these effects were reduced in Computer conditions. The effect of cost uncertainty on gratitude was mediated by the perceived kind intention behind the help. FMRI revealed both shared and differential neurocognitive substrates for evaluating the benefactor's altruistic decisions under risk and ambiguity: both were associated with fear- and anxiety-related processes, involving right lateral orbitofrontal cortex and anterior insula; ambiguity additionally recruited mentalizing- and conflict monitoring-related processes, involving dorsal medial prefrontal cortex and dorsal anterior cingulate cortex. These findings underscore the crucial role of social uncertainty perception in the generation of gratitude.

Phytochrome-interacting factors regulate seedling growth through ABA signaling.

There is a growing body of evidence that abscisic acid (ABA) and the phytochrome-interacting factor (PIF) family of transcription factors interact in light signaling, the regulation of plant growth development, and adaptation to environmental stimuli. In this study, we investigate the role that PIFs play in the regulation of ABA signaling in Arabidopsis thaliana seedlings grown under long-day conditions. We showed that PIFs positively regulate ABA signaling in post-germination seedling growth. We analyzed the DNA-binding sites for PIF3 and PIF5 by DNA-affinity purification sequencing (DAP-seq) genome-wide. The DAP-seq data showed that G-box motif is the direct binding site of PIF3 and PIF5, and a number of ABA responsive genes are potential targets of PIFs, including PYL3, PYL6, PYL12, SnRK2.2, CPK4, CPK6, ABI5, ABF3, and KIN1. Our results provide a basis for understanding the mechanism for PIFs in regulating ABA signal transduction.

Patient-Derived Organoids Predict Chemoradiation Responses of Locally Advanced Rectal Cancer.

Accumulating evidence indicates that patient-derived organoids (PDOs) can predict drug responses in the clinic, but the ability of PDOs to predict responses to chemoradiation in cancer patients remains an open question. Here we generate a living organoid biobank from patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation (NACR) enrolled in a phase III clinical trial. Our co-clinical trial data confirm that rectal cancer organoids (RCOs) closely recapitulate the pathophysiology and genetic changes of corresponding tumors. Chemoradiation responses in patients are highly matched to RCO responses, with 84.43% accuracy, 78.01% sensitivity, and 91.97% specificity. These data imply that PDOs predict LARC patient responses in the clinic and may represent a companion diagnostic tool in rectal cancer treatment.