A novel TOX3-WDR5-ABCG2 signaling axis regulates the progression of colorectal cancer by accelerating stem-like traits and chemoresistance.

The eradication of cancer stem cells (CSCs) with drug resistance confers the probability of local tumor control after chemotherapy or targeted therapy. As the main drug resistance marker, ABCG2 is also critical for colorectal cancer (CRC) evolution, in particular cancer stem-like traits expansion. Hitherto, the knowledge about the expression regulation of ABCG2, in particular its upstream transcriptional regulatory mechanisms, remains limited in cancer, including CRC. Here, ABCG2 was found to be markedly up-regulated in CRC CSCs (cCSCs) expansion and chemo-resistant CRC tissues and closely associated with CRC recurrence. Mechanistically, TOX3 was identified as a specific transcriptional factor to drive ABCG2 expression and subsequent cCSCs expansion and chemoresistance by binding to -261 to -141 segments of the ABCG2 promoter region. Moreover, we found that TOX3 recruited WDR5 to promote tri-methylation of H3K4 at the ABCG2 promoter in cCSCs, which further confers stem-like traits and chemoresistance to CRC by co-regulating the transcription of ABCG2. In line with this observation, TOX3, WDR5, and ABCG2 showed abnormal activation in chemo-resistant tumor tissues of in situ CRC mouse model and clinical investigation further demonstrated the comprehensive assessment of TOX3, WDR5, and ABCG2 could be a more efficient strategy for survival prediction of CRC patients with recurrence or metastasis. Thus, our study found that TOX3-WDR5/ABCG2 signaling axis plays a critical role in regulating CRC stem-like traits and chemoresistance, and a combination of chemotherapy with WDR5 inhibitors may induce synthetic lethality in ABCG2-deregulated tumors.

Selective binding and periodic arrangement of magic boron clusters on monolayer borophene.

The synthesis and characterization of small boron clusters with unique size and regular arrangement are crucial for boron chemistry and two-dimensional borophene materials. In this study, together with theoretical calculations, the joint molecular beam epitaxy and scanning tunneling microscopy experiments achieve the formation of unique B5 clusters on monolayer borophene (MLB) on a Cu(111) surface. The B5 clusters tend to selectively bind to specific sites of MLB with covalent boron-boron bonds in the periodic arrangement, which can be ascribed to the charge distribution and electron delocalization character of MLB and also prohibits nearby co-adsorption of B5 clusters. Furthermore, the close-packed adsorption of B5 clusters would facilitate the synthesis of bilayer borophene, exhibiting domino effect-like growth mode. The successful growth and characterization of uniform boron clusters on a surface enrich the boron-based nanomaterials and reveal the essential role of small clusters during the growth of borophene.

Intercalant-induced V t2g orbital occupation in vanadium oxide cathode toward fast-charging aqueous zinc-ion batteries.

Intercalation-type layered oxides have been widely explored as cathode materials for aqueous zinc-ion batteries (ZIBs). Although high-rate capability has been achieved based on the pillar effect of various intercalants for widening interlayer space, an in-depth understanding of atomic orbital variations induced by intercalants is still unknown. Herein, we design an NH4+-intercalated vanadium oxide (NH4+-V2O5) for high-rate ZIBs, together with deeply investigating the role of the intercalant in terms of atomic orbital. Besides extended layer spacing, our X-ray spectroscopies reveal that the insertion of NH4+ could promote electron transition to 3dxy state of V t2g orbital in V2O5, which significantly accelerates the electron transfer and Zn-ion migration, further verified by DFT calculations. As results, the NH4+-V2O5 electrode delivers a high capacity of 430.0 mA h g-1 at 0.1 A g-1, especially excellent rate capability (101.0 mA h g-1 at 200 C), enabling fast charging within 18 s. Moreover, the reversible V t2g orbital and lattice space variation during cycling are found via ex-situ soft X-ray absorption spectrum and in-situ synchrotron radiation X-ray diffraction, respectively. This work provides an insight at orbital level in advanced cathode materials.

Identification of Synergies in Fe, Co-Coordinated Polyphthalocyanines Scaffolds for Electrochemical CO2 Reduction Reaction.

The synergistic interaction between the isolated metal sites promoted the electrocatalytic activity of the catalysts. However, the structural heterogeneity of the isolated sites makes it challenging to evaluate this effect accurately. In this work, metal-coordinated polyphthalocyanine molecules (Fe-PPc, Co-PPc, FeCo-PPc) with long-range ordered and precise coordination structures are used as a platform to study the synergies of different isolated metal sites in the electrochemical CO2 reduction reaction. The combination means of experimental and theoretical calculation clearly reveal that the coexistence of Fe and Co sites in PPc significantly enhances the conjugation effect of the macrocycle. This enhancement subsequently causes the metal sites to lose more electrons, thereby improving their adsorption of CO2 and facilitating the formation of intermediate *COOH on them. As a result, FeCo-PPc achieves a CO partial current density of about 57.4 mA/cm2 with a high turnover frequency of over 49000 site-1 h-1 at -0.9 V (vs RHE).

Neoadjuvant camrelizumab plus apatinib for locally advanced microsatellite instability-high or mismatch repair-deficient colorectal cancer (NEOCAP): a single-arm, open-label, phase 2 study.

BACKGROUND: PD-1 blockade is highly efficacious for mismatch repair-deficient colorectal cancer in both metastatic and neoadjuvant settings. We aimed to explore the activity and safety of neoadjuvant therapy with PD-1 blockade plus an angiogenesis inhibitor and the feasibility of organ preservation in patients with locally advanced mismatch repair-deficient colorectal cancer. METHODS: We initiated a single-arm, open-label, phase 2 trial (NEOCAP) at Sun Yat-sen University Cancer Center and the Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China. Patients aged 18-75 years with untreated mismatch repair-deficient or microsatellite instability-high or POLE/POLD1-mutated locally advanced colorectal cancer (cT3 or N+ for rectal cancer, and T3 with invasion ≥5mm or T4, with or without N+ for colon cancer) and an Eastern Cooperative Oncology Group performance score of 0-1 were enrolled and given 200 mg camrelizumab intravenously on day 1 and 250 mg apatinib orally from day 1-14, every 3 weeks for 3 months followed by surgery or 6 months if patients did not have surgery. Patients who had a clinical complete response did not undergo surgery and proceeded with a watch-and-wait approach. The primary endpoint was the proportion of patients with a pathological or clinical complete response. Eligible enrolled patients who received at least one cycle of neoadjuvant treatment and had at least one tumour response assessment following the baseline assessment were included in the activity analysis, and patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04715633) and is ongoing. FINDINGS: Between Sept 29, 2020, and Dec 15, 2022, 53 patients were enrolled; one patient was excluded from the activity analysis because they were found to be mismatch repair-proficient and microsatellite-stable. 23 (44%) patients were female and 29 (56%) were male. The median follow-up was 16·4 (IQR 10·5-23·5) months. 28 (54%; 95% CI 35-68) patients had a clinical complete response and 24 of these patients were managed with a watch-and-wait approach, including 20 patients with colon cancer and multiple primary colorectal cancer. 23 (44%) of 52 patients underwent surgery for the primary tumour, and 14 (61%; 95% CI 39-80) had a pathological complete response. 38 (73%; 95% CI 59-84) of 52 patients had a complete response. Grade 3-5 adverse events occurred in 20 (38%) of 53 patients; the most common were increased aminotransferase (six [11%]), bowel obstruction (four [8%]), and hypertension (four [8%]). Drug-related serious adverse events occurred in six (11%) of 53 patients. One patient died from treatment-related immune-related hepatitis. INTERPRETATION: Neoadjuvant camrelizumab plus apatinib show promising antitumour activity in patients with locally advanced mismatch repair-deficient or microsatellite instability-high colorectal cancer. Immune-related adverse events should be monitored with the utmost vigilance. Organ preservation seems promising not only in patients with rectal cancer, but also in those with colon cancer who have a clinical complete response. Longer follow-up is needed to assess the oncological outcomes of the watch-and-wait approach. FUNDING: The National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, and the Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Analyzing the Active Site and Predicting the Overall Activity of Alloy Catalysts.

As one of the potential catalysts, disordered solid solution alloys can offer a wealth of catalytic sites. However, accurately evaluating their activity localization structure and overall activity from each individual site remains a formidable challenge. Herein, an approach based on density functional theory and machine learning was used to obtain a large number of sites of the Pt-Ru alloy as the model multisite catalyst for the hydrogen evolution reaction. Subsequently, a series of statistical approaches were employed to unveil the relationship between the geometric structure and overall activity. Based on the radial frequency distribution of metal elements and the distribution of ΔGH, we have identified the surface and subsurface sites occupied by Pt and Ru, respectively, as the most active sites. Particularly, the concept of equivalent site ratio predicts that the overall activity is highest when the Ru content is 20-30%. Furthermore, a series of Pt-Ru alloys were synthesized to validate the proposed theory. This provides crucial insights into understanding the origin of catalytic activity in alloys and thus will better guide the rational development of targeted multisite catalysts.

Critical Role of Aromatic C(sp2)-H in Boosting Lithium-Ion Storage.

Exploring high-sloping-capacity carbons is of great significance in the development of high-power lithium-ion batteries/capacitors (LIBs/LICs). Herein, an ion-catalyzed self-template method is utilized to synthesize the hydrogen-rich carbon nanoribbon (HCNR), achieving high specific and rate capacity (1144.2/471.8 mAh g-1 at 0.1/2.5 A g-1). The Li+ storage mechanism of the HCNR is elucidated by in situ spectroscopic techniques. Intriguingly, the protonated aromatic sp2-hybridized carbon (C(sp2)-H) can provide additional active sites for Li+ uptake via reversible rehybridization to sp3-C, which is the origin of the high sloping capacity. The presence of this sloping feature suggests a highly capacitance-dominated storage process, characterized by rapid kinetics that facilitates superior rate performance. For practical usage, the HCNR-based LIC device can deliver high energy/power densities of 198.3 Wh kg-1/17.9 kW kg-1. This work offers mechanistic insights on the crucial role of aromatic C(sp2)-H in boosting Li+ storage and opens up new avenues to develop such sloping-type carbons for high-performance rechargeable batteries/capacitors.

Metal-Sulfur Interfaces as the Primary Active Sites for Catalytic Hydrogenations.

The determination of catalytically active sites is crucial for understanding the catalytic mechanism and providing guidelines for the design of more efficient catalysts. However, the complex structure of supported metal nanocatalysts (e.g., support, metal surface, and metal-support interface) still presents a big challenge. In particular, many studies have demonstrated that metal-support interfaces could also act as the primary active sites in catalytic reactions, which is well elucidated in oxide-supported metal nanocatalysts but is rarely reported in carbon-supported metal nanocatalysts. Here, we fill the above gap and demonstrate that metal-sulfur interfaces in sulfur-doped carbon-supported metal nanocatalysts are the primary active sites for several catalytic hydrogenation reactions. A series of metal nanocatalysts with similar sizes but different amounts of metal-sulfur interfaces were first constructed and characterized. Taking Ir for quinoline hydrogenation as an example, it was found that their catalytic activities were proportional to the amount of the Ir-S interface. Further experiments and density functional theory (DFT) calculations suggested that the adsorption and activation of quinoline occurred on the Ir atoms at the Ir-S interface. Similar phenomena were found in p-chloronitrobenzene hydrogenation over the Pt-S interface and benzoic acid hydrogenation over the Ru-S interface. All of these findings verify the predominant activity of metal-sulfur interfaces for catalytic hydrogenation reactions and contribute to the comprehensive understanding of metal-support interfaces in supported nanocatalysts.

A Volcano Correlation between Catalytic Activity for Sulfur Reduction Reaction and Fe Atom Count in Metal Center.

Sulfur reduction reaction (SRR) facilitates up to 16 electrons, which endows lithium-sulfur (Li-S) batteries with a high energy density that is twice that of typical Li-ion batteries. However, its sluggish reaction kinetics render batteries with only a low capacity and cycling life, thus remaining the main challenge to practical Li-S batteries, which require efficient electrocatalysts of balanced atom utilization and site-specific requirements toward highly efficient SRR, calling for an in-depth understanding of the atomic structural sensitivity for the catalytic active sites. Herein, we manipulated the number of Fe atoms in iron assemblies, ranging from single Fe atom to diatomic and triatomic Fe atom groupings, all embedded within a carbon matrix. This led to the revelation of a "volcano peak" correlation between SRR catalytic activity and the count of Fe atoms at the active sites. Utilizing operando X-ray absorption and X-ray diffraction spectroscopies, we observed that polysulfide adsorption-desorption and electrochemical conversion kinetics varied up and down with the incremental addition of even a single iron atom to the catalyst's metal center. Our results demonstrate that the metal center with exactly two iron atoms represents the optimal configuration, maximizing atom utility and adeptly handling the conversion of varied intermediate sulfur species, rendering the Li-S battery with a high areal capacity of 23.8 mAh cm-2 at a high sulfur loading of 21.8 mg cm-2. Our results illuminate the pivotal balance between atom utilization and site-specific requirements for optimal electrocatalytic performance in SRR and diverse electrocatalytic reactions.

Highly Crystalline Iridium-Nickel Nanocages with Subnanopores for Acidic Bifunctional Water Splitting Electrolysis.

Developing efficient bifunctional materials is highly desirable for overall proton membrane water splitting. However, the design of iridium materials with high overall acidic water splitting activity and durability, as well as an in-depth understanding of the catalytic mechanism, is challenging. Herein, we successfully developed subnanoporous Ir3Ni ultrathin nanocages with high crystallinity as bifunctional materials for acidic water splitting. The subnanoporous shell enables Ir3Ni NCs optimized exposure of active sites. Importantly, the nickel incorporation contributes to the favorable thermodynamics of the electrocatalysis of the OER after surface reconstruction and optimized hydrogen adsorption free energy in HER electrocatalysis, which induce enhanced intrinsic activity of the acidic oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). Together, the Ir3Ni nanocages achieve 3.72 A/mgIr(η=350 mV) and 4.47 A/mgIr(η=40 mV) OER and HER mass activity, which are 18.8 times and 3.3 times higher than that of commercial IrO2 and Pt, respectively. In addition, their highly crystalline identity ensures a robust nanostructure, enabling good catalytic durability during the oxygen evolution reaction after surface oxidation. This work provides a new revenue toward the structural design and insightful understanding of metal alloy catalytic mechanisms for the bifunctional acidic water splitting electrocatalysis.

Reticular Ratchets for Directing Electrochemiluminescence.

Electrochemiluminescence (ECL) involves charge transfer between electrochemical redox intermediates to produce an excited state for light emission. Ensuring precise control of charge transfer is essential for decoding ECL fundamentals, yet guidelines on how to achieve this for conventional emitters remain unexplored. Molecular ratchets offer a potential solution, as they enable the directional transfer of energy or chemicals while impeding the reverse movement. Herein, we designed 10 pairs of imine-based covalent organic frameworks as reticular ratchets to delicately manipulate the intrareticular charge transfer for directing ECL transduction from electric and chemical energies. Aligning the donor and acceptor (D-A) directions with the imine dipole effectively facilitates charge migration, whereas reversing the D-A direction impedes it. Notably, the ratchet effect of charge transfer directionality intensified with increasing D-A contrast, resulting in a remarkable 680-fold improvement in the ECL efficiency. Furthermore, dipole-controlled exciton binding energy, electron/hole decay kinetics, and femtosecond transient absorption spectra identified the electron transfer tendency from the N-end toward the C-end of reticular ratchets during ECL transduction. An exponential correlation between the ECL efficiency and the dipole difference was discovered. Our work provides a general approach to manipulate charge transfer and design next-generation electrochemical devices.

Breaking Low-Strain and Deep-Potassiation Trade-Off in Alloy Anodes via Bonding Modulation for High-Performance K-Ion Batteries.

Alloy anode materials have garnered unprecedented attention for potassium storage due to their high theoretical capacity. However, the substantial structural strain associated with deep potassiation results in serious electrode fragmentation and inadequate K-alloying reactions. Effectively reconciling the trade-off between low-strain and deep-potassiation in alloy anodes poses a considerable challenge due to the larger size of K-ions compared to Li/Na-ions. In this study, we propose a chemical bonding modulation strategy through single-atom modification to address the volume expansion of alloy anodes during potassiation. Using black phosphorus (BP) as a representative and generalizing to other alloy anodes, we established a robust P-S covalent bonding network via sulfur doping. This network exhibits sustained stability across discharge-charge cycles, elevating the modulus of K-P compounds by 74%, effectively withstanding the high strain induced by the potassiation process. Additionally, the bonding modulation reduces the formation energies of potassium phosphides, facilitating a deeper potassiation of the BP anode. As a result, the modified BP anode exhibits a high reversible capacity and extended operational lifespan, coupled with a high areal capacity. This work introduces a new perspective on overcoming the trade-off between low-strain and deep-potassiation in alloy anodes for the development of high-energy and stable potassium-ion batteries.

Cetuximab plus FOLFOXIRI versus cetuximab plus FOLFOX as conversion regimen in RAS/BRAF wild-type patients with initially unresectable colorectal liver metastases (TRICE trial): A randomized controlled trial.

BACKGROUND: It remains unclear whether intensification of the chemotherapy backbone in tandem with an anti-EGFR can confer superior clinical outcomes in a cohort of RAS/BRAF wild-type colorectal cancer (CRC) patients with initially unresectable colorectal liver metastases (CRLM). To that end, we sought to comparatively evaluate the efficacy and safety of cetuximab plus FOLFOXIRI (triplet arm) versus cetuximab plus FOLFOX (doublet arm) as a conversion regimen (i.e., unresectable to resectable) in CRC patients with unresectable CRLM. METHODS AND FINDINGS: This open-label, randomized clinical trial was conducted from April 2018 to December 2022 in 7 medical centers across China, enrolling 146 RAS/BRAF wild-type CRC patients with initially unresectable CRLM. A stratified blocked randomization method was utilized to assign patients (1:1) to either the cetuximab plus FOLFOXIRI (n = 72) or cetuximab plus FOLFOX (n = 74) treatment arms. Stratification factors were tumor location (left versus right) and resectability (technically unresectable versus ≥5 metastases). The primary outcome was the objective response rate (ORR). Secondary outcomes included the median depth of tumor response (DpR), early tumor shrinkage (ETS), R0 resection rate, progression-free survival (PFS), overall survival (not mature at the time of analysis), and safety profile. Radiological tumor evaluations were conducted by radiologists blinded to the group allocation. Primary efficacy analyses were conducted based on the intention-to-treat population, while safety analyses were performed on patients who received at least 1 line of chemotherapy. A total of 14 patients (9.6%) were lost to follow-up (9 in the doublet arm and 5 in the triplet arm). The ORR was comparable following adjustment for stratification factors, with 84.7% versus 79.7% in the triplet and doublet arms, respectively (odds ratio [OR] 0.70; 95% confidence intervals [CI] [0.30, 1.67], Chi-square p = 0.42). Moreover, the ETS rate showed no significant difference between the triplet and doublet arms (80.6% (58/72) versus 77.0% (57/74), OR 0.82, 95% CI [0.37, 1.83], Chi-square p = 0.63). Although median DpR was higher in the triplet therapy group (59.6%, interquartile range [IQR], [50.0, 69.7] versus 55.0%, IQR [42.8, 63.8], Mann-Whitney p = 0.039), the R0/R1 resection rate with or without radiofrequency ablation/stereotactic body radiation therapy was comparable with 54.2% (39/72) of patients in the triplet arm versus 52.7% (39/74) in the doublet arm. At a median follow-up of 26.2 months (IQR [12.8, 40.5]), the median PFS was 11.8 months in the triplet arm versus 13.4 months in the doublet arm (hazard ratio [HR] 0.74, 95% CI [0.50, 1.11], Log-rank p = 0.14). Grade ≥ 3 events were reported in 47.2% (35/74) of patients in the doublet arm and 55.9% (38/68) of patients in the triplet arm. The triplet arm was associated with a higher incidence of grade ≥ 3 neutropenia (44.1% versus 27.0%, p = 0.03) and diarrhea (5.9% versus 0%, p = 0.03). The primary limitations of the study encompass the inherent bias in subjective surgical decisions regarding resection feasibility, as well as the lack of a centralized assessment for ORR and resection. CONCLUSIONS: The combination of cetuximab with FOLFOXIRI did not significantly improve ORR compared to cetuximab plus FOLFOX. Despite achieving an enhanced DpR, this improvement did not translate into improved R0 resection rates or PFS. Moreover, the triplet arm was associated with an increase in treatment-related toxicity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03493048.

Realization of the Giant Pyroelectric Response via Modulated Polar Structures.

Among pyroelectric materials, Bi0.5Na0.5TiO3 (BNT)-based relaxors are particularly noteworthy due to their significant polarization fluctuation near the depolarization temperature (Td), resulting in a large pyroelectric response. What has been overlooked is the dynamic behavior of inherent polar structures, particularly the temperature-dependent evolution of polar nanoregions (PNRs), which significantly impacts the pyroelectric behavior. Herein, based on the large pyroelectric response origination (the ferroelectric-relaxor phase transition), the mixed nonergodic and ergodic relaxor (NR+ER) critical state is constructed, which is believed to trigger the easily fluctuating polarization state with excellent pyroelectric response. Composition engineering (with Li+, Sr2+, and Ta5+) strategically controls the relaxor process and modulates the dynamic behavior of inherent polar structures by the random field effect. The pyroelectric coefficient of more than 1441 µCm-2K-1 at room temperature (RT), more than 9221 µCm-2K-1 (RT), and ≈107911 µCm-2K-1 (Td) are achieved in the Li+-doped sample, the Sr2+-doped sample, and the (Li++Ta5+) co-doped sample, respectively. This work earns the highest RT pyroelectric coefficient in BNT-based relaxors, which is suitable for pyroelectric applications. Furthermore, it provides a strategy for modulating the pyroelectric performance of BNT-based relaxors.

Universal Intercalation/Alloying Hybrid Mechanism with -ICOHP Criterion in MAX Toward Steadily Ascending Lithium-Ion Batteries.

Profiting from the unique atomic laminated structure, metallic conductivity, and superior mechanical properties, transition metal carbides and nitrides named MAX phases have shown great potential as anodes in lithium-ion batteries. However, the complexity of MAX configurations poses a challenge. To accelerate such application, a minus integrated crystal orbital Hamilton populations descriptor is innovatively proposed to rapidly evaluate the lithium storage potential of various MAX, along with density functional theory computations. It confirms that surface A-element atoms bound to lithium ions have odds of escaping from MAX. Interestingly, the activated A-element atoms enhance the reversible uptake of lithium ions by MAX anodes through an efficient alloying reaction. As an experimental verification, the charge compensation and SnxLiy phase evolution of designed Zr2SnC MAX with optimized structure is visualized via in situ synchrotron radiation XRD and XAFS technique, which further clarifies the theoretically expected intercalation/alloying hybrid storage mechanism. Notably, Zr2SnC electrodes achieve remarkably 219.8% negative capacity attenuation over 3200 cycles at 1 A g-1. In principle, this work provides a reference for the design and development of advanced MAX electrodes, which is essential to explore diversified applications of the MAX family in specific energy fields.

N-methyl Formamide Electrolyte Additive Enabling Highly Reversible Zn Anodes.

Parasitic side reactions and dendrites formation hinder the application of aqueous zinc ion batteries due to inferior cycling life and low reversibility. Against this background, N-methyl formamide (NMF), a multi-function electrolyte additive is applied to enhance the electrochemical performance. Studied via advanced synchrotron radiation spectroscopy and DFT calculations, the NMF additive simultaneously modifies the Zn2+ solvation structure and ensures uniform zinc deposition, thus suppressing both parasitic side reactions and dendrite formation. More importantly, an ultralong cycling life of 3115 h in the Zn||Zn symmetric cell at a current density of 0.5 mA cm-2 is achieved with the NMF additive. Practically, the Zn||PANI full cell utilizing NMF electrolyte shows better rate and cycling performance compared to the pristine ZnSO4 aqueous electrolyte. This work provides useful insights for the development of high-performance aqueous metal batteries.

MFR-DTA: a multi-functional and robust model for predicting drug-target binding affinity and region.

MOTIVATION: Recently, deep learning has become the mainstream methodology for drug-target binding affinity prediction. However, two deficiencies of the existing methods restrict their practical applications. On the one hand, most existing methods ignore the individual information of sequence elements, resulting in poor sequence feature representations. On the other hand, without prior biological knowledge, the prediction of drug-target binding regions based on attention weights of a deep neural network could be difficult to verify, which may bring adverse interference to biological researchers. RESULTS: We propose a novel Multi-Functional and Robust Drug-Target binding Affinity prediction (MFR-DTA) method to address the above issues. Specifically, we design a new biological sequence feature extraction block, namely BioMLP, that assists the model in extracting individual features of sequence elements. Then, we propose a new Elem-feature fusion block to refine the extracted features. After that, we construct a Mix-Decoder block that extracts drug-target interaction information and predicts their binding regions simultaneously. Last, we evaluate MFR-DTA on two benchmarks consistently with the existing methods and propose a new dataset, sc-PDB, to better measure the accuracy of binding region prediction. We also visualize some samples to demonstrate the locations of their binding sites and the predicted multi-scale interaction regions. The proposed method achieves excellent performance on these datasets, demonstrating its merits and superiority over the state-of-the-art methods. AVAILABILITY AND IMPLEMENTATION: https://github.com/JU-HuaY/MFR.

Temporal compressive edge imaging enabled by a lensless diffuser camera.

Lensless imagers based on diffusers or encoding masks enable high-dimensional imaging from a single-shot measurement and have been applied in various applications. However, to further extract image information such as edge detection, conventional post-processing filtering operations are needed after the reconstruction of the original object images in the diffuser imaging systems. Here, we present the concept of a temporal compressive edge detection method based on a lensless diffuser camera, which can directly recover a time sequence of edge images of a moving object from a single-shot measurement, without further post-processing steps. Our approach provides higher image quality during edge detection, compared with the "conventional post-processing method." We demonstrate the effectiveness of this approach by both numerical simulation and experiments. The proof-of-concept approach can be further developed with other image post-processing operations or versatile computer vision assignments toward task-oriented intelligent lensless imaging systems.

Terahertz-triggered ultrafast nonlinear optical activities in two-dimensional centrosymmetric PtSe2.

The nonlinear mechanisms of polarization and optical fields can induce extensive responses in materials. In this study, we report on two kinds of nonlinear mechanisms in the topological semimetal PtSe2 crystal under the excitation of intense terahertz (THz) pulses, which are manipulated by the real and imaginary parts of the nonlinear susceptibility of PtSe2. Regarding the real part, the broken inversion symmetry of PtSe2 is achieved through a THz-electric-field polarization approach, which is characterized by second harmonic generation (SHG) measurements. The transient THz-laser-induced SHG signal occurs within 100 fs and recombines to the equilibrium state within 1 ps, along with a high signal-to-noise ratio (∼51 dB) and a high on/off ratio (∼102). Regarding the imaginary part, a nonlinear absorption change can be generated in the media. We reveal a THz-induced absorption enhancement in PtSe2 via nonlinear transmittance measurements, and the sheet conductivity can be modulated up to 42% by THz electric fields in our experiment. Therefore, the THz-induced ultrafast nonlinear photoresponse reveals the application potential of PtSe2 in photonic and optoelectronic devices in the THz technology.

Synthesis of Carboranylated Dihydropyrrolo[1,2-a]quinoxalines and Dihydroindolo[1,2-a]quinoxalines by BF3·OEt2-Catalyzed Heterocyclization of C-Formyl-o-carboranes and Investigation of Their Oxidation Stability.

A BF3·OEt2-catalyzed synthesis of carboranylated dihydropyrrolo[1,2-a]quinoxalines and dihydroindolo[1,2-a]quinoxalines in 30-99% yields is presented through the heterocyclization of various C-modified C-formyl-o-carboranes with 1-(2-aminophenyl)-pyrroles/indoles. A systematic comparative investigation of their oxidation stability in air confirmed that 4-carboranyl-4,5-dihydropyrrolo[1,2-a]quinoxaline had better stability than the 4-phenyl analogue. A cage-deboronation reaction for N-acetyl-substituted carboranylated dihydropyrrolo[1,2-a]quinoxaline produced the corresponding 7,8-nido-carborane cesium salt. A kinetic resolution was also realized to obtain an optically pure carboranylated N-heterocycle scaffold bearing a carborane cage carbon-bonded chiral stereocenter.