Thalamocortical contributions to working memory processes during the n-back task.

Working memory allows individuals to temporally maintain and manipulate information that is no longer accessible from the sensorium. Whereas prior studies have detailed frontoparietal contributions to working memory processes, less emphasis has been placed on subcortical regions, in particular the human thalamus. The thalamus has a complex anatomy that consists of several distinct nuclei, many of which have dense anatomical connectivity with frontoparietal regions, and thus might play an important yet underspecified role for working memory. The goal of our study is to characterize the detailed functional neuroanatomy of the human thalamus and thalamocortical interactions during the n-back task. To that end, we analyzed an n-back fMRI dataset consisting of 395 subjects from the Human Connectome Project (HCP). We found that thalamic nuclei in the anterior, medial, ventral lateral, and posterior medial thalamus showed stronger evoked responses in response to higher working memory load. Activity in most thalamic nuclei were only modulated by working memory load, but not by categorical membership of the memorized stimuli, suggesting that thalamic function supports domain-general processing for working memory. To determine whether thalamocortical interactions contribute to cortical activity for working memory, we employed an activity flow mapping analysis to test whether thalamocortical interactions can predict cortical task activity patterns. In support, this data-driven thalamocortical interaction model explained a significant amount of variance in the observed cortical activity patterns modulated by working memory load. Our results suggest that the anterior, medial, and posterior medial thalamus, and their associated thalamocortical interactions, contribute to the modulations of distributed cortical activity during working memory.

The hybrid oncolytic peptide NTP-385 potently inhibits adherent cancer cells by targeting the nucleus.

The use of oncolytic peptides with activity against a wide range of cancer entities as a new and promising cancer therapeutic strategy has drawn increasing attention. The oncolytic peptide LTX-315 derived from bovine lactoferricin (LfcinB) was found to be highly effective against suspension cancer cells, but not adherent cancer cells. In this study, we tactically fused LTX-315 with rhodamine B through a hybridization strategy to design and synthesize a series of nucleus-targeting hybrid peptides and evaluated their activity against adherent cancer cells. Thus, four hybrid peptides, NTP-212, NTP-217, NTP-223 and NTP-385, were synthesized. These hybrid peptides enhanced the anticancer activity of LTX-315 in a panel of adherent cancer cell lines by 2.4- to 37.5-fold. In model mice bearing B16-F10 melanoma xenografts, injection of NTP-385 (0.5 mg per mouse for 3 consecutive days) induced almost complete regression of melanoma, prolonged the median survival time and increased the overall survival. Notably, the administered dose of NTP-385 was only half the effective dose of LTX-315. We further revealed that unlike LTX-315, which targets the mitochondria, NTP-385 disrupted the nuclear membrane and accumulated in the nucleus, resulting in the transfer of a substantial amount of reactive oxygen species (ROS) from the cytoplasm to the nucleus through the fragmented nuclear membrane. This ultimately led to DNA double-strand break (DSB)-mediated intrinsic apoptosis. In conclusion, this study demonstrates that hybrid peptides obtained from the fusion of LTX-315 and rhodamine B enhance anti-adherent cancer cell activity by targeting the nucleus and triggering DNA DSB-mediated intrinsic apoptosis. This study also provides an advantageous reference for nucleus-targeting peptide modification.

DIC/Oxyma-based accelerated synthesis and oxidative folding studies of centipede toxin RhTx.

Coupling reagents play crucial roles in the iterative construction of amide bonds for the synthesis of peptides and peptide-based derivatives. The novel DIC/Oxyma condensation system featured with the low risk of explosion displayed remarkable abilities to inhibit racemization, along with efficient coupling efficiency in both manual and automated syntheses. Nevertheless, an ideal reaction molar ratio in DIC/Oxyma condensation system and the moderate reaction temperature by manual synthesis remain to be further investigated. Herein, the synthetic efficiencies of different reaction ratios between DIC and Oxyma under moderate reaction temperature were systematically evaluated. The robustness and efficiency of DIC/Oxyma condensation system are validated by the rapid synthesis of linear centipede toxin RhTx. Different folding strategies were applied for the construction of disulfide bridges in RhTx, which was further confirmed in assays of circular dichroism and patch-clamp electrophysiology evaluation. This work establishes the DIC/Oxyma-based accelerated synthesis of peptides under moderate condensation conditions, which is especially useful for the manual synthesis of peptides. Besides, the strategy presented here provides robust technical supports for the large-scale synthesis and oxidative folding of RhTx.

HaCYC2c regulating the heteromorphous development and functional differentiation of florets by recognizing HaNDUA2 in sunflower.

KEY MESSAGE: The overexpression of HaCYC2c and its regulation on HaNDUA2 through transcriptional recognition are important for regulating the heteromorphous development and functional differentiation of ray and disc florets in sunflower. Flower symmetry is closely related to pollinator recruitment and individual fecundity for higher plants and is the main feature used to identify flower type in angiosperms. In sunflower, HaCYC2c regulates floral organ development and floral symmetry, but the specific detail remains unclear. In this study, sunflower long petal mutant (lpm) with HaCYC2c insertion mutation was used to investigate the regulating role of HaCYC2c in the morphogenesis of florets and the transformation of floral symmetry through phenotype, transcriptome, qRT-PCR, and possible protein-gene interactions analyses. Results showed that HaCYC2c was overexpressed after an insertion into the promoter region. This gene could recognize the cis-acting element GGTCCC in the promoter region of HaNDUA2 that might regulate HaNDUA2 and affect other related genes. As a consequence, the abnormal elongation of disc petals and the degradation of male reproductive system occurred at the early development of floral organ in sunflower. Furthermore, this insertion mutation resulted in floral symmetry transformation, from actinomorphy to zygomorphy, thereby making the tubular disc florets transformed into ray-like disc florets in sunflower lpm. The findings suggested that the overexpression of HaCYC2c and its control of HaNDUA2 through transcriptional recognition might be an important regulating node of the heteromorphous development and functional differentiation for ray and disc florets in sunflower. This node contributes to the understanding of the balance between pollinator recruitment capacity of ray florets and fertility of disc florets for the optimization of reproductive efficiency and enhancement of species competitiveness in sunflower.

Acute stress reduces the emotional attentional blink: Evidence from human electrophysiology.

The present study is the first to examine the time-dependent mechanism of acute stress on emotional attentional blink (EAB) with event-related potential (ERP) measures. We explored the stage characteristics of stress affecting EAB, whether it affects the early selective attention process (marked by early posterior negativity) or the late working memory consolidation (marked by late positive potential). Sixty-one healthy participants were exposed to either a Trier Social Stress Test (TSST) or a control condition, and salivary cortisol was measured to reflect the stress effect. ERPs were recorded during an attentional blink (AB) paradigm in which target one (T1) were negative or neutral images. Results showed stress generally reduced AB effects. Specifically, stress promoted the early selective attention process of target two (T2) following a neutral T1 but did not affect T2 consolidation into working memory. Correlational analyses further confirmed the positive effect of cortisol and negative emotional state on AB performance. Moreover, the ERP results of acute stress on AB conformed to the trade-off effect between T1 and T2; that is, stress reduced T1 late working memory consolidation and improved T2 early selective attention process. These findings further demonstrated that stress did not change the central resource limitation of AB. In general, stress generates a dissociable effect on AB early- and late-stage processing; namely, acute stress reduce the AB effect mainly from the improvement of participants' overall ability to select the targets in the early stage.

Tunable Metal-Organic Frameworks Based on 8-Connected Metal Trimers for High Ethane Uptake.

Metal trimers [M3 (O/OH)](OOCR)6 are among the most important structural building blocks. From these trimers, a great success has been achieved in the design of 6- or 9-connected framework materials with various topological features and outstanding gas-sorption properties. In comparison, 8-connected trimer-based metal-organic frameworks (MOFs) are rare. Given multiple competitive pathways for the formation of 6- or 9-connected frameworks, it remains challenging to identify synthetic or structural parameters that can be used to direct the self-assembly process toward trimer-based 8-connected materials. Here, a viable strategy called angle bending modulation is revealed for creating a prototypical MOF type based on 8-connected M3 (OH)(OOCR)5 (Py-R)3 trimers (M = Zn, Co, Fe). As a proof of concept, six members in this family are synthesized using three types of ligands (CPM-80, -81, and -82). These materials do not possess open-metal sites and show excellent uptake capacity for various hydrocarbon gas molecules and inverse C2 H6 /C2 H4 selectivity. CPM-81-Co, made from 2,5-furandicarboxylate and isonicotinate, features selectivity of 1.80 with high uptake capacity for ethane (123 cm3 g-1 ) and ethylene (113 cm3 g-1 ) at 298 K and 1 bar.

A Strategy for Constructing Pore-Space-Partitioned MOFs with High Uptake Capacity for C2 Hydrocarbons and CO2.

Introduction of pore partition agents into hexagonal channels of MIL-88 type (acs topology) endows materials with high tunability in gas sorption. Here, we report a strategy to partition acs framework into pacs (partitioned acs) crystalline porous materials (CPM). This strategy is based on insertion of in situ synthesized 4,4'-dipyridylsulfide (dps) ligands. One third of open metal sites in the acs net are retained in pacs MOFs; two thirds are used for pore-space partition. The Co2 V-pacs MOFs exhibit near or at record high uptake capacities for C2 H2 , C2 H4 , C2 H6 , and CO2 among MOFs. The storage capacity of C2 H2 is 234 cm3 g-1 (298 K) and 330 cm3 g-1 (273 K) at 1 atm for CPM-733-dps (the Co2 V-BDC form, BDC=1,4-benzenedicarboxylate). These high uptake capacities are accomplished with low heat of adsorption, a feature desirable for low-energy-cost adsorbent regeneration. CPM-733-dps is stable and shows no loss of C2 H2 adsorption capacity following multiple adsorption-desorption cycles.

From MOF-74-Zn to Triazolate-Directed Nonsymmetric Assembly of Chiral Zn6 @Zn6 Clusters.

The creation of new cluster building blocks, as well as new ligand coordination modes, are among the most effective ways to develop new framework materials. Yet, large and chiral clusters are both difficult to create and relatively few. Here, by studying the competing coordination of different azolates against carboxylate and combined carboxylate/phenolate, it is shown that the impact of azolates in the MOF-74 synthesis system differs dramatically, leading to the synthesis of MOF-74, UTSA-74, and CPM-72 for 2-methylimidazole, 1,2,4-triazole, and 1,2,3-triazole, respectively. The new CPM-72 contains a novel chiral Zn12 triazolate cluster, which features a trigonal-prismatic Zn6 core inside an octahedral Zn6 shell. In contrast with MOF-74 with fully deprotonated and symmetrically bonded 2,5-dihydroxyterephthalic acid (H4 DOBDC), H4 DOBDC adopts an unusual nonsymmetric bonding mode in CPM-72 (carboxylate only at one end and carboxylate/phenolate at the other), resulting in a highly porous and intrinsically chiral 3D framework. The nonsymmetric bonding mode by H4 DOBDC, apparently dictated by the chiral Zn12 cluster, can be replicated with 2-hydroxyterephthalic acid (H3 OBDC), leading to the synthesis of porous isoreticular CPM-73.

Attentional blink affected by acute stress in women: The role of affective stimuli and attentional resources.

The role of attentional resources and affective stimuli on temporal selective attention in the rapid serial visual presentation (RSVP) paradigm under acute stress was explored among women. Seventy-three female undergraduates were randomly assigned to the Trier Social Stress Test (TSST) group or control group. We found that when the first target was negative, stress increased its accuracy. Stress promoted the recognition of neutral target two (T2) only at lag2, and there was no interaction with theemotionality of target one (T1). In addition, the accumulated effect of stress enhanced temporal selective attention, predominately 20-40 min after the TSST task; cortisol concentration during this time period could significantly predict AB task performance. In summary, when attentional resources were severely insufficient, individuals under stress were more able to focus on the current target; that is, stress facilitated selective attention. A novel result was that participants were exempt from the affective influence of previous targets, which may have been caused by activation of the autonomic nervous system and gender differences.

Enabling Homochirality and Hydrothermal Stability in Zn4O-Based Porous Crystals.

The [Zn4O]6+ cluster is well-known to form the archetypal MOF-5 topology with dicarboxylate ligands. Here we report two new materials (CPM-300 and -301) that show dramatic alteration of topological and chemical behaviors of [Zn4O]6+ clusters. In CPM-300, [Zn4O]6+ untypically forms the MIL-88/MOF-235 type framework with a small pentane-ring-based chiral dicarboxylate. In contrast, in CPM-301, when mediated by [Zn9(btz)12]6+ clusters (btz = benzotriazolate), the MOF-5 topology is regenerated with the same chiral ligand, albeit with alternating [Zn4O]6+ and [Zn9(btz)12]6+ clusters. Importantly, both CPM-300 and CPM-301 are homochiral, hydrothermally stable in boiling water and alcohol, and thermally stable to 440 °C or higher. It is concluded that small methyl groups on the chiral ligand is sufficiently powerful to shield [Zn4O]6+ clusters from degradation by water, even at high temperatures. These results reveal a promising platform for the development of a new class of cluster-based homochiral and hydrothermally stable porous materials.

Charge- and Size-Complementary Multimetal-Induced Morphology and Phase Control in Zeolite-Type Metal Chalcogenides.

Zeolite-type chalcogenides are desirable due to their integration between porosity and semiconductivity. CPM-120, with super-sodalite topology (Zeolite Structure Code: RWY), is among the few zeolite-type chalcogenides with permanent porosity, and is the only chalcogenide with a zeolite code. Importantly, the RWY-type has evolved into a platform for studying properties of porous chalcogenides. Yet so far, few studies have been made to probe the effects of synthetic parameters and framework compositions on this platform. Here, we probe the effects of the third metal type (Ga3+ , In3+ , Cd2+ , and Sn4+ ) on the Zn2+ /Ge4+ /S2- platform. We find that charge-complementary and size-compatible Ga3+ leads to the synthesis of CPM-120-ZnGaGeS which is the first trimetallic zeolite-type chalcogenide, with improved crystal morphology and reproducibility. We also find that charge-compatible and size-complementary cations (Cd2+ or Sn4+ ) can induce an abrupt phase transition from super-sodalite to super-diamond, also with unprecedented trimetallic T2 clusters. For In3+ , which is dual-complementary (charge and size), a gradual phase transition is observed with increasing In3+ amount. Furthermore, by controlling the cluster composition, tunable band gaps can be realized. These materials show promising properties such as high CO2 uptake (4.32 mmol cm-3 , 298 K, 1 bar) and high photocatalytic activity.

Homo-Helical Rod Packing as a Path Toward the Highest Density of Guest-Binding Metal Sites in Metal-Organic Frameworks.

In porous materials, metal sites with coordinate solvents offer opportunities for many applications, especially those promoted by host-guest chemistry, but such sites are especially hard to create for Li-based materials, because unlike transition metals, lithium does not usually possess a high-enough coordination number for both framework construction and guest binding. This challenge is addressed by mimicking the functional group ratio and metal-to-ligand charge ratio in MOF-74. A family of rod-packing lithium-organic frameworks (CPM-47, CPM-48, and CPM-49) were obtained. These materials exhibit an extremely high density of guest-binding lithium sites. Also unusual is the homo-helical rod-packing in the CPM series, as compared to the hetero-helical rod packing by helices of opposite handedness in MOF-74. This work demonstrates new chemical and structural possibilities in developing a record-setting high density of guest-binding metal sites in inorganic-organic porous materials.

Selective Ion Exchange and Photocatalysis by Zeolite-Like Semiconducting Chalcogenide.

The development of novel photocatalysts usually centers on features such as band structures, various nano-, micro-, or macro-forms, and composites in efforts to tune their light absorption and charge separation efficiency. In comparison, the selectivity of photocatalysts with respect to features of reactants such as size and charge has received much less attention, in part due to the difficulty in designing semiconducting photocatalysts with uniform pore size. Here, we use crystalline porous chalcogenides as a platform to probe reactant selectivity in photocatalytic processes. The 3-in-1 integration of high surface area, uniform porosity, and favorable band structures in such chalcogenides makes them excellent candidates for efficient and selective photocatalytic processes. We show that their photocatalytic activity and selectivity are closely related to their differing affinity and selectivity for different guest species. In particular, unlike common solid-state photocatalysts with neutral framework, the anionic nature of the porous chalcogenide framework used here endows them with a high degree of selectivity for cationic species in both guest exchange and closely coupled photocatalytic transformation of such guests. Another interesting discovery is the observation of an unusual ion exchange process involving a transient state of over-saturation of exchanged ions, which can be explained by a transition from an initially kinetically controlled process to a subsequent thermodynamically controlled one. This work is part of ongoing efforts to contribute to the development of a new generation of crystalline porous photocatalysts with custom-designed selectivity for various reactants or products.

Integrating Zeolite-Type Chalcogenide with Titanium Dioxide Nanowires for Enhanced Photoelectrochemical Activity.

Developing photoanodes with efficient visible-light harvesting and excellent charge separation still remains a key challenge in photoelectrochemical water splitting. Here zeolite-type chalcogenide CPM-121 is integrated with TiO2 nanowires to form a heterostructured photoanode, in which crystalline CPM-121 particles serve as a visible light absorber and TiO2 nanowires serve as an electron conductor. Owing to the small band gap of chalcogenides, the hybrid electrode demonstrates obvious absorption in visible-light range. Electrochemical impedance spectroscopy (EIS) shows that electron transport in the hybrid electrode has been significantly facilitated due to the heterojunction formation. A >3-fold increase in photocurrent is observed on the hybrid electrode under visible-light illumination when it is used as a photoanode in a neutral electrolyte without sacrificial agents. This study opens up a new avenue to explore the potential applications of crystalline porous chalcogenide materials for solar-energy conversion in photoelectrochemistry.

Cation-Exchanged Zeolitic Chalcogenides for CO2 Adsorption.

We report here the intrinsic advantages of a special family of porous chalcogenides for CO2 adsorption in terms of high selectivity of CO2/N2, large uptake capacity, and robust structure due to their first-ever unique integration of the chalcogen-soft surface, high porosity, all-inorganic crystalline framework, and the tunable charge-to-volume ratio of exchangeable cations. Although tuning the CO2 adsorption properties via the type of exchangeable cations has been well-studied in oxides and MOFs, little is known about the effects of inorganic exchangeable cations in porous chalcogenides, in part because ion exchange in chalcogenides can be very sluggish and incomplete due to their soft character. We have demonstrated that, through a methodological change to progressively tune the host-guest interactions, both facile and nearly complete ion exchange can be accomplished. Herein, a series of cation-exchanged zeolitic chalcogenides (denoted as M@RWY) were studied for the first time for CO2 adsorption. Samples were prepared through a sequential ion-exchange strategy, and Cs+-, Rb+-, and K+-exchanged samples demonstrated excellent CO2 adsorption performance. Particularly, K@RWY has the superior CO2/N2 selectivity with the N2 adsorption even undetected at either 298 or 273 K. It also has the large uptake of 6.3 mmol/g (141 cm3/g) at 273 K and 1 atm with an isosteric heat of 35-41 kJ mol-1, the best among known porous chalcogenides. Moreover, it permits a facile regeneration and exhibits an excellent recyclability, as shown by the multicycling adsorption experiments. Notably, K@RWY also demonstrates a strong tolerance toward water.

Cooperative Crystallization of Heterometallic Indium-Chromium Metal-Organic Polyhedra and Their Fast Proton Conductivity.

Metal-organic polyhedra (MOPs) or frameworks (MOFs) based on Cr(3+) are notoriously difficult to synthesize, especially as crystals large enough to be suitable for characterization of the structure or properties. It is now shown that the co-existence of In(3+) and Cr(3+) induces a rapid crystal growth of large single crystals of heterometallic In-Cr-MOPs with the [M8L12] (M=In/Cr, L=dinegative 4,5-imidazole-dicarboxylate) cubane-like structure. With a high concentration of protons from 12 carboxyl groups decorating every edge of the cube and an extensive H-bonded network between cubes and surrounding H2O molecules, the newly synthesized In-Cr-MOPs exhibit an exceptionally high proton conductivity (up to 5.8×10(-2) S cm(-1) at 22.5 °C and 98% relative humidity, single crystal).

Three Rounds of Stability-Guided Optimization and Systematical Evaluation of Oncolytic Peptide LTX-315.

Oncolytic peptides represent promising novel candidates for anticancer treatments. In our efforts to develop oncolytic peptides possessing both high protease stability and durable anticancer efficiency, three rounds of optimization were conducted on the first-in-class oncolytic peptide LTX-315. The robust synthetic method, in vitro and in vivo anticancer activity, and anticancer mechanism were investigated. The D-type peptides represented by FXY-12 possessed significantly improved proteolytic stability and sustained anticancer efficiency. Strikingly, the novel hybrid peptide FXY-30, containing one FXY-12 and two camptothecin moieties, exhibited the most potent in vitro and in vivo anticancer activities. The mechanism explorations indicated that FXY-30 exhibited rapid membranolytic effects and induced severe DNA double-strand breaks to trigger cell apoptosis. Collectively, this study not only established robust strategies to improve the stability and anticancer potential of oncolytic peptides but also provided valuable references for the future development of D-type peptides-based hybrid anticancer chemotherapeutics.

A robust porous metal-organic framework with a new topology that demonstrates pronounced porosity and high-efficiency sorption/selectivity properties of small molecules.

A robust porous metal-organic framework (MOF), [Co(3)(ndc)(HCOO)(3)(µ(3)-OH)(H(2)O)](n) (1) (H(2)ndc=5-(4-pyridyl)-isophthalic acid), was synthesized with pronounced porosity. MOF 1 contained two different types of nanotubular channels, which exhibited a new topology with the Schlafli symbol of {4(2).6(5).8(3)}{4(2).6}. MOF 1 showed high-efficiency for the selective sorption of small molecules, including the energy-correlated gases of H(2), CH(4), and CO(2), and environment-correlated steams of alcohols, acetone, and pyridine. Gas-sorption experiments indicated that MOF 1 exhibited not only a high CO(2)-uptake (25.1 wt % at 273 K/1 bar) but also the impressive selective sorption of CO(2) over N(2) and CH(4). High H(2)-uptake (2.04 wt % at 77 K/1 bar) was also observed. Moreover, systematic studies on the sorption of steams of organic molecules displayed excellent capacity for the sorption of the homologous series of alcohols (C(1)-C(5)), acetone, pyridine, as well as water.

Hybrid peptide NTP-217 triggers ROS-mediated rapid necrosis in liver cancer cells by induction of mitochondrial leakage.

Liver cancer is the third leading cause of cancer-associated mortality globally, and >830,000 patients with liver cancer undergoing treatment succumbed to the disease in 2020, which indicates the urgent need to develop a more effective anti-liver cancer drug. In our previous study, nucleus-targeting hybrid peptides obtained from the fusion of LTX-315 and the rhodamine B group possessed potent anti-adherent cancer cell activity. Hybrid peptides accumulated in the cell nucleus and damaged the nuclear membrane, resulting in the transfer of reactive oxygen species (ROS) from the cytoplasm to the nucleus and the induction of apoptosis. However, the source of the high concentration of ROS within the cytoplasm is unclear. Moreover, although our previous study demonstrated that hybrid peptides possessed potent anticancer activity against adherent cancer cells, their efficacy on liver cancer remained unexplored. The current study found that the hybrid peptide NTP-217 killed liver cancer cells after 4-h treatment with a half-maximal inhibitory concentration of 14.6-45.7 µM. NTP-217 could stably accumulate in the liver tumor tissue and markedly inhibited liver tumor growth in mice. Furthermore, NTP-217 destroyed mitochondria and induced the leakage of mitochondrial contents, resulting in the generation of a substantial quantity of ROS. Unlike the apoptosis induced by 24 h of treatment by NTP-217, 4 h of treatment caused ROS-mediated necrotic cell death. These findings suggested that short-time treatment with hybrid peptides could trigger ROS-mediated rapid necrosis in liver cancer cells, and provided a basis for the future development of hybrid peptides as anti-liver cancer agents.

A new strategy for constructing a disulfide-functionalized ZIF-8 analogue using structure-directing ligand-ligand covalent interaction.

Inter-ligand van der Waals forces play a key role in the synthesis of different ZIF types. Here we report an unusual case involving covalent inter-ligand interactions through disulfide bond formation in a ZIF-8 analogue. It exhibits high CO2 uptake and stepwise adsorption of light hydrocarbons with potential applications in ethane/ethylene separation.