Delivery of Cu(II) and Mn(II) by polydopamine-modified nanoparticles for combined photothermal and chemotherapy.

Chemodynamic therapy (CDT) has been recognized as an emerging therapeutic strategy. It has attracted considerable attention in recent years as it can generate the most harmful reactive oxygen species (ROS)-hydroxyl radicals (•OH) through the Fenton reaction or a Fenton-like reaction under the catalysis of versatile metal cations, such as, Fe(II), Fe(III), Cu(I), Mn(II), and Mn(III). However, a large number of reducing species (e.g., GSH) in tumors inhibit the therapeutic effects of CDT. This study proposes a nanocarrier strategy that can release versatile metal cations in the initial stage to consume the reducing substances, which can be convenient for subsequent CDT treatment. A novel nano-delivery system based on H-MnO2@PDA/Cu-CD@Ad-TK-Ad@Ploy-CD (abbreviated as MNZ) was proposed to resolve the above problems. Herein, hollow mesoporous manganese dioxide nanoparticles (H-MnO2) were coated with PDA and modified with copper ions on the surface of PDA. The PDA was then functionalized with ß-cyclodextrin (ß-CD) substitutions that were further assembled with N-((1S,3R,5S)-adamantan-1-yl)-3-((2-((3-(((3s,5s,7s)-adamantan-1-yl)amino)-3-oxopropyl)thio)propan-2-yl)thio)propenamide (Ad-TK-Ad). Poly-CD was assembled with CD to improve the stability of the reactor. The MNZ nanotheranostic platform can release Cu(II) and Mn(II), which could react with intracellular GSH to consume the reducing substances in tumors. Subsequently, H2O2 can be converted into •OH, and the effect is improved with increasing temperatures. Cytotoxicity of MNZ (200 µg mL-1) was studied by cell counting kit-8 (CCK-8) assay using HeLa cells as the models. Results indicated that cell viability was clearly reduced to 22% by the nanoparticles alone, to 18% by the nanoparticles with H2O2, and to 9% by the nanoparticles with H2O2 and NIR, under weak acidic condition (pH 6.8). This work provides a beneficial exploration for the application of nano-delivery strategies for combined photothermal and chemodynamic therapy agents.

hnRNPU is required for spermatogonial stem cell pool establishment in mice.

The continuous regeneration of spermatogonial stem cells (SSCs) underpins spermatogenesis and lifelong male fertility, but the developmental origins of the SSC pool remain unclear. Here, we document that hnRNPU is essential for establishing the SSC pool. In male mice, conditional loss of hnRNPU in prospermatogonia (ProSG) arrests spermatogenesis and results in sterility. hnRNPU-deficient ProSG fails to differentiate and migrate to the basement membrane to establish SSC pool in infancy. Moreover, hnRNPU deletion leads to the accumulation of ProSG and disrupts the process of T1-ProSG to T2-ProSG transition. Single-cell transcriptional analyses reveal that germ cells are in a mitotically quiescent state and lose their unique identity upon hnRNPU depletion. We further show that hnRNPU could bind to Vrk1, Slx4, and Dazl transcripts that have been identified to suffer aberrant alternative splicing in hnRNPU-deficient testes. These observations offer important insights into SSC pool establishment and may have translational implications for male fertility.

Prevalence and detection methodology for preliminary exploration of NTRK fusion in gastric cancer from a single-center retrospective cohort.

The fusion of neurotrophic tyrosine receptor kinase (NTRK) is a novel target for cancer therapy and offers hope for patients with gastric cancer (GC). However, there are few studies on the prevalence and detection methods of NTRK fusions in GC. In this study, we used immunohistochemistry (IHC) as a screening method to select cases for molecular testing and evaluated the effectiveness of IHC, fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS). We retrospectively collected 1970 patients with GC. Pan-TRK IHC was conducted in all cases, and three cases were positive: one with strong and diffuse cytoplasmic staining, while two with weak cytoplasmic staining. All three cases were validated using NTRK1/2/3 FISH. FISH results revealed a single 3' signal of NTRK1 in 95% of the tumor cells in the first case, while the remaining two cases were negative. NGS confirmed LMNA-NTRK1 fusion in the first case, with no gene fusion detected in the other two cases. Out of 46 negative controls, one had a non-functional fusion of IGR-NTRK1, and four had point mutations. The case with LMNA-NTRK1 fusion were negative for pMMR, EBV, HER2, and AFP. The pan-TRK IHC showed a 33.33% (1/3) concordance rate with RNA-based NGS. If the criterion for positivity was 3+ cytoplasmic staining, the agreement between IHC and RNA-based NGS was 100% (1/1). In conclusion, the incidence of NTRK fusion in GC is extremely low (0.05%). If the criteria are strict, pan-TRK IHC is highly effective for screening NTRK fusions. FISH could complement NGS detection, particularly when NTRK fusion is detected by DNA sequencing. NTRK fusion in GC may not be limited to specific subtypes.

Telomeric function and regulation during male meiosis in mice and humans.

BACKGROUND: Telomeres are unique structures situated at the ends of chromosomes. Preserving the structure and function of telomeres is essential for maintaining genomic stability and promoting genetic diversity during male meiosis in mammals. MATERIAL-METHODS: This review compiled recent literature on the function and regulation of telomeres during male meiosis in both mice and humans, and also highlighted the critical roles of telomeres in reproductive biology and medicine. RESULTS-DISCUSSION: Various structures, consisting of the LINC complex (SUN-KASH), SPDYA-CDK2, TTM trimer (TERB1-TERB2-MAJIN), and shelterin, are critical in controlling telomeric activities, such as nuclear envelope attachment and bouquet formation. Other than telomere-related proteins, cohesins and genes responsible for regulating telomere function are also highlighted, though the exact mechanism remains unclear. The gene-mutant mouse models with meiotic defects directly reveal the essential roles of telomeres in male meiosis. Recently reported mutant genes associated with telomere activity in clinical practice have also been illustrated in detail. CONCLUSIONS: Proper regulation of telomere activities is essential for male meiosis progression in mice and humans.

Strong Interfacial Chemical Bonding in Regulating Electron Transfer and Stabilizing Catalytic Sites in a Metal-Semiconductor Schottky Junction for Enhanced Photocatalysis.

The weak electronic interaction at metal-photocatalyst heterointerfaces often compromises solar-to-fuel performance. Here, a trifunctional Schottky junction, involving chemically stabilized ultrafine platinum nanoparticles (Pt NPs, ≈3 nm in diameter) on graphitic carbon nitride nanosheets (CNs) is proposed. The Pt-CN electronic interaction induces a 1.5% lattice compressive strain in Pt NPs and maintains their ultrafine size, effectively preventing their aggregation during photocatalytic reactions. Density functional theory calculations further demonstrate a significant reduction in the Schottky barrier at the chemically bonded CN-Pt heterointerface, facilitating efficient interfacial electron transfer, as supported by femtosecond transient absorption spectra (fs-TAS) measurements. The combined effects of lattice strain, stabilized Pt NPs, and efficient interfacial charge transport collaboratively enhance the photocatalytic performance, leading to over an 11-fold enhancement in visible light H2 production (8.52 mmol g-1 h-1) compared to the CN nanosheets with the in situ photo-deposited Pt NPs (0.76 mmol g-1 h-1). This study highlights the effectiveness of strong metal-semiconductor electronic interactions and underscores the potential for developing high-efficiency photocatalysts.

ADAD2 interacts with RNF17 in P-bodies to repress the Ping-pong cycle in pachytene piRNA biogenesis.

Pachytene piRNA biogenesis is a hallmark of the germline, distinct from another wave of pre-pachytene piRNA biogenesis with regard to the lack of a secondary amplification process known as the Ping-pong cycle. However, the underlying molecular mechanism and the venue for the suppression of the Ping-pong cycle remain elusive. Here, we showed that a testis-specific protein, ADAD2, interacts with a TDRD family member protein RNF17 and is associated with P-bodies. Importantly, ADAD2 directs RNF17 to repress Ping-pong activity in pachytene piRNA biogenesis. The P-body localization of RNF17 requires the intrinsically disordered domain of ADAD2. Deletion of Adad2 or Rnf17 causes the mislocalization of each other and subsequent Ping-pong activity derepression, secondary piRNAs overproduced, and disruption of P-body integrity at the meiotic stage, thereby leading to spermatogenesis arrested at the round spermatid stage. Collectively, by identifying the ADAD2-dependent mechanism, our study reveals a novel function of P-bodies in suppressing Ping-pong activity in pachytene piRNA biogenesis.

An exploration of gastric cancer with heterogeneous mismatch repair status.

Survival benefits or symptom alleviation from immune checkpoint blockade therapy can be seen in microsatellite instability-high (MSI-H) cases. However, genetic heterogeneity within a specific subgroup of MSI-H tumors may be associated with poor response and prognosis. We investigated the molecular changes and microsatellite status of the cases with heterogeneous MMR protein staining by polymerase chain reaction (PCR) and next-generation sequencing (NGS). Data from 3723 patients with gastric cancer were retrospectively analyzed to determine the mismatch repair (MMR) status by performing immunohistochemical staining of four major MMR proteins (MLH1, PMS2, MSH2, and MSH6). When heterogeneous MMR protein staining result was positive, PCR and NGS were performed. Heterogeneous MMR protein staining was observed in 12 cases. In microsatellite stable (MSS) cases, TP53 mutation appeared to accompany heterogeneous staining (HS) of MLH1. However, TP53 variation was not observed with MSI-H occurrence. Cases showing heterogeneous MSH6 protein staining revealed MSH6 mutations. Some cases with the same MMR protein staining set had varying MSI results. In one case whose primary and metastatic foci presented MLH1-HS and PMS2-HS, the microsatellite status was classified as MSS and MSI-H, respectively. Moreover, HS was also found in multiple biopsies and surgical specimens. This study found a preliminary relationship between heterogeneously stained MSH6 or MLH1 proteins and their gene mutations, as well as between MSI-H/TP53 - and MSS/TP53 + tumors. The microsatellite status of patients with heterogeneous MMR protein staining is unpredictable. Given the heterogeneity of mismatch repair, microsatellite status should be assessed for all specimens if sufficient specimens can be obtained.

Modulating the Rise and Decay Dynamics of Upconversion Luminescence through Controlling Excitations.

Different from organic dye/quantum dot possessing one luminescent center, upconversion luminescence (UCL) is actually a statistic of temporal behaviors of countless individual activators. Our experimental results have shown that the rise and decay dynamics of UCL is directly associated with the relative contribution of sensitizer-to-activator energy transfer and energy migration among sensitizers, which can be physically modulated by simply tuning the excitation laser. Therefore, dynamic UCL with record-wide 20-fold lifetime, ≈70-fold red-to-green intensity ratio, and reversibly definable emission color is easily realized by just modulating the excitation laser. Moreover, this generally applicable strategy only requires a simplest-possible UCL system whereas prevalent material engineering such as complicated composition design, sophisticated core-shell construction, or tedious chemical synthesis, is no longer needed.

Physicochemical characteristics and in vitro digestibility of starches from colored quinoa (Chenopodium quinoa) varieties.

The quinoa flour processing is mostly subject to the properties of starch. Starches from four colored quinoa varieties, including white quinoa (QS-W), yellow quinoa (QS-Y), red (QS-R), and black (QS-B), were compared with respect to their physicochemical properties and in vitro digestibility. Results indicated that QS-B exhibited the highest content of amylose (8.14%) (p < 0.05). All starch samples exhibited as irregular sphere with a particle size less than 3 µm. Results of the FT-IR and X-ray showed that the short-range order of the four quinoa starches exhibited no significant difference; all starches showed a typical A-type diffractrometric pattern and was not affected by seed color, and QS-Y had the highest relative crystallinity (34.3%) (p < 0.05). In addition, QS-W reflected the highest solubility (6.32%) and QS-Y showed the highest swelling power (19.45 g/g) (p < 0.05). QS-Y also presented a higher ΔH value (11.46 J/g) (p < 0.05), while QS-R peak temperature and peak G' were the lowest. Besides, QS-B had the highest slow-digestible starch (SDS) and resistant starch (RS) content, while the lowest estimated glycemic index (eGI) value (p < 0.05). Also, there was a negative correlation between hydrolysis rates and amylose content of quinoa starch. PRACTICAL APPLICATION: Due to the low gelatinization temperature of quinoa starch, it can be used to both produce and improve instant and fast food products. Quinoa starch particles are small, and Pickering emulsions and additives have potential application values. Red quinoa contains easily digestible starch, which can be a good food choice for infants and the elderly, while white quinoa starch has less swelling power and can be used in noodle products. The results of this study can help to underpin the study of quinoa nonstarch components versus starch component.

Mitochondrial regulation during male germ cell development.

Mitochondria tailor their morphology to execute their specialized functions in different cell types and/or different environments. During spermatogenesis, mitochondria undergo continuous morphological and distributional changes with germ cell development. Deficiencies in these processes lead to mitochondrial dysfunction and abnormal spermatogenesis, thereby causing male infertility. In recent years, mitochondria have attracted considerable attention because of their unique role in the regulation of piRNA biogenesis in male germ cells. In this review, we describe the varied characters of mitochondria and focus on key mitochondrial factors that play pivotal roles in the regulation of spermatogenesis, from primordial germ cells to spermatozoa, especially concerning metabolic shift, stemness and reprogramming, mitochondrial transformation and rearrangement, and mitochondrial defects in human sperm. Further, we discuss the molecular mechanisms underlying these processes.

Templated-Construction of Hollow MoS2 Architectures with Improved Photoresponses.

Despite the outstanding optoelectronic properties of MoS2 and its analogues, synthesis of such materials with desired features including fewer layers, arbitrary hollow structures, and particularly specifically customized morphologies, via inorganic reactions has always been challenging. Herein, using predesigned lanthanide-doped upconversion luminescent materials (e.g., NaYF4:Ln) as templates, arbitrary MoS2 hollow structures with precisely defined morphologies, widely variable dimensions, and very small shell thickness (≈2.5 nm) are readily constructed. Most importantly, integration of the near-infrared-responsive template significantly improves the photoresponse of up to 600 fold in device made of NaYF4:Yb/Er@MoS2 compared with that of MoS2 nanosheets under 980 nm laser illumination. Multichannel optoelectronic device is further fabricated by simply changing luminescent ions in the template, e.g., NaYF4:Er@MoS2, operating at 1532 nm light excitation with a 276-fold photoresponse enhancement. The simple chemistry, easy operation, high reliability, variable morphologies, and wide universality represent the most important advantages of this novel strategy that has not been accessed before.

Self-Assembly of Perovskite CsPbBr3 Quantum Dots Driven by a Photo-Induced Alkynyl Homocoupling Reaction.

Herein, we report the facile growth of three-dimensional CsPbBr3 perovskite supercrystals (PSCs) self-assembled from individual CsPbBr3 perovskite quantum dots (PQDs). By varying the carbon chain length of a surface-bound ligand molecule, 1-alkynyl acid, different morphologies of PSCs were obtained accompanied by an over 1000-fold photoluminescence improvement compared with that of PQDs. Systematic analyses have shown, for the first time, that under UV irradiation, CsBr, the byproduct formed during PQDs synthesis, could effectively catalyze the homocoupling reaction between two alkynyl groups, which further worked as a driving force to push forward the self-assembly of PQDs.

Design for Brighter Photon Upconversion Emissions via Energy Level Overlap of Lanthanide Ions.

The perfect energy level overlap of 2H11/2, 4S3/2, and 4F9/2 in Er3+ ions with those of 5F3, 5F4/5S2, and 5F5 in adjacently codoped Ho3+ ions allows efficient interenergy transfer. Therefore, in addition to routine activators, Er3+ or Ho3+ can further act as sensitizers to transfer the upconverted energy to nearby Ho3+ or Er3+, resulting in enhanced upconversion luminescence due to the emission overlap. Proper codoping of Er3+/Ho3+ or Ho3+/Er3+ obviously elevates the maximum doping concentration (thus producing additional upconverted photons) to a level higher than that causing luminescence quenching and significantly enhances upconversion emissions compared with those of singly Er3+ or Ho3+-doped host materials. Indeed, the so-far strongest red upconversion emission under 1532 nm excitation was obtained in LiYF4:Er/Ho@LiYF4 nanoparticles and Ho3+-sensitized Er3+ upconversion emissions excited by 1150 nm laser was simultaneously discovered. With great enhancement compared with that of singly Ho3+ doped counterparts, this work demonstrates the generality and rationality of our design strategy.

Erbium(iii)-based metal-organic frameworks with tunable upconversion emissions.

A series of lanthanide-based metal-organic frameworks (Ln-MOFs) with significantly improved and tunable upconversion emissions were prepared. Y-MOFs co-doped with Yb3+/Er3+ ions have exhibited characteristic upconversion emissions at 520, 545, and 658 nm under 980 nm laser excitation, the intensities of which vary with Yb3+/Er3+ concentrations. In addition, experimental results have indicated that an excited state absorption mechanism is responsible for the upconversion process of Y-MOF:Yb/Er materials. This study has provided a novel design principle and experimental basis for the preparation of luminescent Ln-MOF materials.

Interconversion between KSc2F7:Yb/Er and K2NaScF6:Yb/Er nanocrystals: the role of chemistry.

Scandium (Sc) sits at a unique position in the periodic table, i.e., the junction of the top of the rare earth column and the beginning of the transition metal row. Studies have shown that Sc-based nanomaterials are very sensitive to the surrounding chemical environment. A simple adjustment of the chemical reaction conditions such as temperature, surfactant molecules, and solvents (e.g., oleic acid (OA) or 1-octadecene (OD)) can easily lead to different products in terms of chemical composition and phase structure. Herein, under purposely adjusted reaction conditions, we have investigated the interconversion process between two representative Sc-based nanomaterials, that is, nanocrystals of orthorhombic KSc2F7:Yb/Er and cubic K2NaScF6:Yb/Er, both of which have characteristic red upconversion luminescence and high similarity in chemical composition and phase structure. Experimental results have indicated that conversion from KSc2F7:Yb/Er to K2NaScF6:Yb/Er may start from the edge of the nanocrystal where K+ in KSc2F7:Yb/Er was gradually substituted by the post-introduced Na+ in the solution and finally KSc2F7:Yb/Er nanorods were broken and K2NaScF6:Yb/Er nanocubes were formed. On the other hand, a simple variation of the OA : OD ratio facilitates the dissolution of K2NaScF6:Yb/Er and subsequent crystallization of KSc2F7:Yb/Er during the opposite conversion process. Possible chemical reaction mechanisms were further developed to elucidate the interconversion details. Meanwhile, the variation of the upconversion luminescence such as emission intensity, red to green ratio, and lifetime is interpreted to monitor the conversion progress at corresponding stages, which is highly consistent with the scenario discussed above.

Synergetic Exfoliation and Lateral Size Engineering of MoS2 for Enhanced Photocatalytic Hydrogen Generation.

Generally, exfoliation is an efficient strategy to create more edge site so as to expose more active sites on molybdenum disulphide (MoS2 ). However, the lateral sizes of the resultant MoS2 monolayers are relatively large (≈50-500 nm), which retain great potential to release more active sites. To further enhance the catalytic performance of MoS2 , a facile cascade centrifugation-assisted liquid phase exfoliation method is introduced here to fabricate monolayer enriched MoS2 nanosheets with nanoscale lateral sizes. The as-prepared MoS2 revealed a high monolayer yield of 36% and small average lateral sizes ranging from 42 to 9 nm under gradient centrifugations, all exhibiting superior catalytic performances toward photocatalytic H2 generation. Particularly, the optimized monolayer MoS2 with an average lateral size of 9 nm achieves an apparent quantum efficiency as high as 77.2% on cadmium sulphide at 420 nm. This work demonstrates that the catalytic performances of MoS2 could be dramatically enhanced by synergistic exfoliation and lateral size engineering as a result of increased density of active sites and shortened charge diffusion distance, paving a new way for design and fabrication of transition-metal dichalcogenides-based materials in the application of hydrogen generation.

Photoassisted Construction of Holey Defective g-C3 N4 Photocatalysts for Efficient Visible-Light-Driven H2 O2 Production.

Holey defective g-C3 N4 photocatalysts, which are easily prepared via a novel photoassisted heating process, are reported. The photoassisted treatment not only helps to create abundant holes, endowing g-C3 N4 with more exposed catalytic active sites and crossplane diffusion channels to shorten the diffusion distance of both reactants from the surface to bulk and charge carriers from the bulk to surface, but also introduces nitrogen vacancies in the tri-s-triazine repeating units of g-C3 N4 , inducing the narrowing of intrinsic bandgap and the formation of defect states within bandgap to extend the visible-light absorption range and suppress the radiative electron-hole recombination. As a result, the holey defective g-C3 N4 photocatalysts show much higher photocatalytic activity for H2 O2 production with optimized enhancement up to ten times higher than pristine bulk g-C3 N4 . The newly developed synthetic strategy adopted here enables the sufficient utilization of solar energy and shows rather promising for the modification of other materials for efficient energy-related applications.

One-pot synthesis of CdS nanocrystals hybridized with single-layer transition-metal dichalcogenide nanosheets for efficient photocatalytic hydrogen evolution.

Exploration of low-cost and earth-abundant photocatalysts for highly efficient solar photocatalytic water splitting is of great importance. Although transition-metal dichalcogenides (TMDs) showed outstanding performance as co-catalysts for the hydrogen evolution reaction (HER), designing TMD-hybridized photocatalysts with abundant active sites for the HER still remains challenge. Here, a facile one-pot wet-chemical method is developed to prepare MS2-CdS (M=W or Mo) nanohybrids. Surprisedly, in the obtained nanohybrids, single-layer MS2 nanosheets with lateral size of 4-10 nm selectively grow on the Cd-rich (0001) surface of wurtzite CdS nanocrystals. These MS2-CdS nanohybrids possess a large number of edge sites in the MS2 layers, which are active sites for the HER. The photocatalytic performances of WS2-CdS and MoS2-CdS nanohybrids towards the HER under visible light irradiation (>420 nm) are about 16 and 12 times that of pure CdS, respectively. Importantly, the MS2-CdS nanohybrids showed enhanced stability after a long-time test (16 h), and 70% of catalytic activity still remained.

Dye-sensitized Pt@TiO2 core-shell nanostructures for the efficient photocatalytic generation of hydrogen.

Pt@TiO2 core-shell nanostructures were prepared through a hydrothermal method. The dye-sensitization of these Pt@TiO2 core-shell structures allows for a high photocatalytic activity for the generation of hydrogen from proton reduction under visible-light irradiation. When the dyes and TiO2 were co-excited through the combination of two irradiation beams with different wavelengths, a synergic effect was observed, which led to a greatly enhanced H2 generation yield. This is attributed to the rational spatial distribution of the three components (dye, TiO2, Pt), and the vectored transport of photogenerated electrons from the dye to the Pt particles via the TiO2 particle bridge.

Au@TiO2-CdS ternary nanostructures for efficient visible-light-driven hydrogen generation.

We report a new type of Au@TiO2-CdS ternary nanostructure by decorating CdS nanoparticles onto Au@TiO2 core-shell structures. In comparison to that of binary structures such as CdS-TiO2 and Au@TiO2, these ternary nanostructures exhibit a remarkably high photocatalytic H2-generation rate under visible-light irradiation. The enhanced photocatalytic activity is attributed to the unique ternary design, which builds up a transfer path for the photoexcited electrons of CdS to the core Au particles via the TiO2 nanocrystal bridge and thus effectively suppresses the electron-hole recombination on the CdS photocatalyst. This internal electron-transfer pathway (CdS → TiO2 â†’ Au) eliminates the need for the postdeposition of the metal cocatalyst because the core Au nanoparticles can act as the interior active catalyst for proton reduction toward hydrogen evolution. We believe that our work demonstrates a promising way for the rational design of metal-semiconductor hybrid photocatalysts that can achieve a high photocatalytic efficiency for use in solar fuels production.