Infection with Clonorchis sinensis (Cobbold, 1875) Metacercariae in Fish from the East Lake of Wuhan: Freshwater Fish in Urban Lakes May Act as Infection Sources of Liver Fluke.

The liver fluke disease caused by Clonorchis sinensis is one of the most serious food-borne parasitic diseases in China. Many freshwater fish and shrimps can be infected with C. sinensis metacercariae as the second intermediate hosts in endemic regions. Owing to the lack of infected humans and the good administration of pet dogs and cats in cities of non-endemic regions, few fish are expected to be infected with C. sinensis metacercariae in urban lakes. To determine the infection of C. sinensis metacercariae in freshwater fish and shrimps in urban lakes, a total of 18 fish species and one shrimp species were investigated in the East Lake of Wuhan City. Metacercariae were isolated by artificial digestive juice and identified using morphology and rDNA-ITS2 sequences. Five species of fish, Pseudorasbora parva, Ctenogobius giurinus, Squalidus argentatus, Hemiculter leuciclus, and Rhodeus spp., were infected with C. sinensis metacercariae. The overall prevalence of C. sinensis was 32.5%. The highest prevalence was found in P. parva with 57.9%, while S. argentatus exhibited the highest mean abundance (13.9). Apart from the C. sinensis metacercariae, four species of other trematode metacercariae were also identified across twelve fish species in total. Owing to the consumption of undercooked fish and feeding cats with small fish caught by anglers, there is a potential risk that the small fish infected with C. sinensis metacercariae may act as an infection source to spread liver fluke. Given the complete life cycle of C. sinensis, stray cats and rats were inferred to act as the important final hosts of C. sinensis in urban lakes in non-endemic areas.

Proteomics study the potential targets for Rifampicin-resistant spinal tuberculosis.

Introduction: The escalating global surge in Rifampicin-resistant strains poses a formidable challenge to the worldwide campaign against tuberculosis (TB), particularly in developing countries. The frequent reports of suboptimal treatment outcomes, complications, and the absence of definitive treatment guidelines for Rifampicin-resistant spinal TB (DSTB) contribute significantly to the obstacles in its effective management. Consequently, there is an urgent need for innovative and efficacious drugs to address Rifampicin-resistant spinal tuberculosis, minimizing the duration of therapy sessions. This study aims to investigate potential targets for DSTB through comprehensive proteomic and pharmaco-transcriptomic analyses. Methods: Mass spectrometry-based proteomics analysis was employed to validate potential DSTB-related targets. PPI analysis confirmed by Immunohistochemistry (IHC) and Western blot analysis. Results: The proteomics analysis revealed 373 differentially expressed proteins (DEPs), with 137 upregulated and 236 downregulated proteins. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses delved into the DSTB-related pathways associated with these DEPs. In the context of network pharmacology analysis, five key targets-human leukocyte antigen A chain (HLAA), human leukocyte antigen C chain (HLA-C), HLA Class II Histocompatibility Antigen, DRB1 Beta Chain (HLA-DRB1), metalloproteinase 9 (MMP9), and Phospholipase C-like 1 (PLCL1)-were identified as pivotal players in pathways such as "Antigen processing and presentation" and "Phagosome," which are crucially enriched in DSTB. Moreover, pharmaco-transcriptomic analysis can confirm that 58 drug compounds can regulate the expression of the key targets. Discussion: This research confirms the presence of protein alterations during the Rifampicin-resistant process in DSTB patients, offering novel insights into the molecular mechanisms underpinning DSTB. The findings suggest a promising avenue for the development of targeted drugs to enhance the management of Rifampicin-resistant spinal tuberculosis.

A Transformable Specific-Responsive Peptide for One-Step Synergistic Therapy of Bladder Cancer.

Synergistic therapy has shown greater advantages compared with monotherapy. However, the complex multiple-administration plan and potential side effects limit its clinical application. A transformable specific-responsive peptide (TSRP) is utilized to one-step achieve synergistic therapy integrating anti-tumor, anti-angiogenesis and immune response. The TSRP is composed of: i) Recognition unit could specifically target and inhibit the biological function of FGFR-1; ii) Transformable unit could self-assembly and trigger nanofibers formation; iii) Reactive unit could specifically cleaved by MMP-2/9 in tumor micro-environment; iv) Immune unit, stimulate the release of immune cells when LTX-315 (Immune-associated oncolytic peptide) exposed. Once its binding to FGFR-1, the TSRP could cleaved by MMP-2/9 to form the nanofibers on the cell membrane, with a retention time of up to 12 h. Through suppressing the phosphorylation levels of ERK 1/2 and PI3K/AKT signaling pathways downstream of FGFR-1, the TSRP significant inhibit the growth of tumor cells and the formation of angioginesis. Furthermore, LTX-315 is exposed after TSRP cleavage, resulting in Calreticulin activation and CD8+ T cells infiltration. All above processes together contribute to the increasing survival rate of tumor-bearing mice by nearly 4-folds. This work presented a unique design for the biological application of one-step synergistic therapy of bladder cancer.

Bispecific fibrous glue synergistically boosts vascular normalization and antitumor immunity for advanced renal carcinoma therapy.

Immune checkpoint blockade therapy represented by programmed cell death ligand 1 (PD-L1) inhibitor for advanced renal carcinoma with an objective response rate (ORR) in patients is less than 20%. It is attributed to abundant tumoral vasculature with abnormal structure limiting effector T cell infiltration and drug penetration. We propose a bispecific fibrous glue (BFG) to regulate tumor immune and vascular microenvironments simultaneously. The bispecific precursor glue peptide-1 (pre-GP1) can penetrate tumor tissue deeply and self-assemble into BFG in the presence of neuropilin-1 (NRP-1) and PD-L1. The resultant fibrous glue is capable of normalizing tumoral vasculature as well as restricting immune escape. The pre-GP1 retains a 6-fold higher penetration depth than that of antibody in the multicellular spheroids (MCSs) model. It also shows remarkable tumor growth inhibition (TGI) from 19% to 61% in a murine advanced large tumor model compared to the clinical combination therapy. In addition, in the orthotopic renal tumor preclinical model, the lung metastatic nodules are reduced by 64% compared to the clinically used combination. This pre-GP1 provides a promising strategy to control the progression and metastasis of advanced renal carcinoma.

Association Between Arthritis and the Risk of Depressive Symptoms in Middle-Aged and Older Adults: A Nationwide Population-Based Study.

Background: Arthritis patients often endure the development of depressive symptoms, significantly impacting their quality of life. However, current research on the correlation between arthritis and depressive symptoms remains limited, suggesting inconsistent findings. Objective: This study investigated this correlation using data from the 2018 China Health and Retirement Longitudinal Study (CHARLS) to explore the connection between arthritis and depressive symptoms among middle-aged and elderly individuals. Methods: This retrospective study encompassed a matched cohort of 13,318 Chinese adults aged ≥ 45 years, consisting of 6,925 individuals with depressive symptoms and 6,393 without, drawn from CHARLS. A logistic regression model was employed to examine the intricate relationship between arthritis and depressive symptoms within this diverse population. Through careful consideration of covariates such as age, residence, marital status, educational level, current drinking habits, and current smoking status, our objective was to promote a nuanced understanding of the complex relationship between arthritis and the prevalence of depressive symptoms. Results: Among the 13,318 respondents, the average age (Mean ± SD) was 60 ± 10 years. The prevalence rates of arthritis, depressive symptoms, and the combination of arthritis with depressive symptoms were 32%, 52%, and 40%, respectively. After adjusting for all covariates, including age, residence, marital status, educational level, current drinkers, and current smokers, the risk of developing depressive symptoms in patients with arthritis remained significantly higher (OR=1.31, 95% CI 1.11-1.48, P = .021) compared to those without arthritis. Conclusions: This study establishes a significant association between arthritis and the development of depressive symptoms in middle-aged and older adults. Arthritis emerges as a potential risk factor, emphasizing the need for targeted interventions to enhance mental well-being in this population.

Inducing mitochondriopathy-like damages by transformable nucleopeptide nanoparticles for targeted therapy of bladder cancer.

Mitochondriopathy inspired adenosine triphosphate (ATP) depletions have been recognized as a powerful way for controlling tumor growth. Nevertheless, selective sequestration or exhaustion of ATP under complex biological environments remains a prodigious challenge. Harnessing the advantages of in vivo self-assembled nanomaterials, we designed an Intracellular ATP Sequestration (IAS) system to specifically construct nanofibrous nanostructures on the surface of tumor nuclei with exposed ATP binding sites, leading to highly efficient suppression of bladder cancer by induction of mitochondriopathy-like damages. Briefly, the reported transformable nucleopeptide (NLS-FF-T) self-assembled into nuclear-targeted nanoparticles with ATP binding sites encapsulated inside under aqueous conditions. By interaction with KPNA2, the NLS-FF-T transformed into a nanofibrous-based ATP trapper on the surface of tumor nuclei, which prevented the production of intracellular energy. As a result, multiple bladder tumor cell lines (T24, EJ and RT-112) revealed that the half-maximal inhibitory concentration (IC50) of NLS-FF-T was reduced by approximately 4-fold when compared to NLS-T. Following intravenous administration, NLS-FF-T was found to be dose-dependently accumulated at the tumor site of T24 xenograft mice. More significantly, this IAS system exhibited an extremely antitumor efficacy according to the deterioration of T24 tumors and simultaneously prolonged the overall survival of T24 orthotopic xenograft mice. Together, our findings clearly demonstrated the therapeutic advantages of intracellular ATP sequestration-induced mitochondriopathy-like damages, which provides a potential treatment strategy for malignancies.

A Millimeter-Wave Broadband Multi-Mode Substrate-Integrated Gap Waveguide Traveling-Wave Antenna with Orbit Angular Momentum.

Orbit angular momentum (OAM) has been considered a new dimension for improving channel capacity in recent years. In this paper, a millimeter-wave broadband multi-mode waveguide traveling-wave antenna with OAM is proposed by innovatively utilizing the transmitted electromagnetic waves (EMWs) characteristic of substrate-integrated gap waveguides (SIGWs) to introduce phase delay, resulting in coupling to the radiate units with a phase jump. Nine "L"-shaped slot radiate elements are cut in a circular order at a certain angle on the SIGW to generate spin angular momentum (SAM) and OAM. To generate more OAM modes and match the antenna, four "Π"-shaped slot radiate units with a 90° relationship to each other are designed in this circular array. The simulation results show that the antenna operates at 28 GHz, with a -10 dB fractional bandwidth (FBW) = 35.7%, ranging from 25.50 to 35.85 GHz and a VSWR ≤ 1.5 dB from 28.60 to 32.0 GHz and 28.60 to 32.0 GHz. The antenna radiates a linear polarization (LP) mode with a gain of 9.3 dBi at 34.0~37.2 GHz, a l = 2 SAM-OAM (i.e., circular polarization OAM (CP-OAM)) mode with 8.04 dBi at 25.90~28.08 GHz, a l = 1 and l = 2 hybrid OAM mode with 5.7 dBi at 28.08~29.67 GHz, a SAM (i.e., left/right hand circular polarization (L/RHCP) mode with 4.6 dBi at 29.67~30.41 GHz, and a LP mode at 30.41~35.85 GHz. In addition, the waveguide transmits energy with a bandwidth ranging from 26.10 to 38.46 GHz. Within the in-band, only a quasi-TEM mode is transmitted with an energy transmission loss |S21| ≤ 2 dB.

A Design Method and Application of Meta-Surface-Based Arbitrary Passband Filter for Terahertz Communication.

A meta-surface-based arbitrary bandwidth filter realization method for terahertz (THz) future communications is presented. The approach involves integrating a meta-surface-based bandstop filter into an ultra-wideband (UWB) bandpass filter and adjusting the operating frequency range of the meta-surface bandstop filter to realize the design of arbitrary bandwidth filters. It effectively addresses the complexity of designing traditional arbitrary bandwidth filters and the challenges in achieving impedance matching. To underscore its practicality, the paper employs silicon substrate integrated gap waveguide (SSIGW) and this method to craft a THz filter. To begin, design equations for electromagnetic band gap (EBG) structures were developed in accordance with the requirements of through-silicon via (TSV) and applied to the design of the SSIGW. Subsequently, this article employs equivalent transmission line models and equivalent circuits to conduct theoretical analyses for both the UWB passband and the meta-surface stopband portions. The proposed THz filter boasts a center frequency of 0.151 THz, a relative bandwidth of 6.9%, insertion loss below 0.68 dB, and stopbands exceeding 20 GHz in both upper and lower ranges. The in-band group delay is 0.119 ± 0.048 ns. Compared to reported THz filters, the SSIGW filter boasts advantages such as low loss and minimal delay, making it even more suitable for future wireless communication.

Association of depressive symptoms and dementia among middle-aged and elderly community-dwelling adults: Results from the China Health and Retirement Longitudinal Study (CHARLS).

BACKGROUND: There has been a long-standing debate on whether depressive symptoms are associated with dementia. The aim of this study was to examine whether depressive symptoms were associated with a high risk for dementia in Chinese adults. METHODS: A total of 13,426 Chinese adults (≥45 years old) from the China Health and Retirement Longitudinal Study (CHARLS) baseline were selected for analysis. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression Scale (CESD-10). Dementia was assessed by the Community Screening Instrument for Dementia (CSI-D). When using linear regression for sensitivity analysis, there is still a correlation between depressive symptoms and dementia. RESULTS: Of the 13,426 respondents, the mean (SD) age was 60 (10) years old. The prevalence of depressive symptoms and dementia among participants was 38 % (n = 945) and 18.3 % (n = 2457), respectively. After fully adjusted for demographic factors, health behavior and psychological factors, living and working conditions factors, social network factors, and social policy factors, the cross-sectional analyses showed that depressive symptoms had an increased risk of dementia (OR = 1.390, 95%CI: 1.253-1.543), compared with those without depressive symptoms. In addition, sensitivity analyses of the association between depressive symptoms and dementia were unchanged when reanalyzing using linear regression. CONCLUSIONS: In this study, depression symptoms may be associated with dementia. Regardless of whether depressive symptoms acts as a dementia risk factor or an early symptom, monitoring depressive symptoms is crucial to watch for potential dementia onset.

In vivo assembly enhanced binding effect augments tumor specific ferroptosis therapy.

Emerging evidence indicates that the activation of ferroptosis by glutathione peroxidase 4 (GPX4) inhibitors may be a prominent therapeutic strategy for tumor suppression. However, the wide application of GPX4 inhibitors in tumor therapy is hampered due to poor tumor delivery efficacy and the nonspecific activation of ferroptosis. Taking advantage of in vivo self-assembly, we develop a peptide-ferriporphyrin conjugate with tumor microenvironment specific activation to improve tumor penetration, endocytosis and GPX4 inhibition, ultimately enhancing its anticancer activity via ferroptosis. Briefly, a GPX4 inhibitory peptide is conjugated with an assembled peptide linker decorated with a pH-sensitive moiety and ferriporphyrin to produce the peptide-ferriporphyrin conjugate (Gi-F-CAA). Under the acidic microenvironment of the tumor, the Gi-F-CAA self-assembles into large nanoparticles (Gi-F) due to enhanced hydrophobic interaction after hydrolysis of CAA, improving tumor endocytosis efficiency. Importantly, Gi-F exhibits substantial inhibition of GPX4 activity by assembly enhanced binding (AEB) effect, augmenting the oxidative stress of ferriporphyrin-based Fenton reaction, ultimately enabling antitumor properties in multiple tumor models. Our findings suggest that this peptide-ferriporphyrin conjugate design with AEB effect can improve the therapeutic effect via induction of ferroptosis, providing an alternative strategy for overcoming chemoresistance.

An In Vivo Self-Assembled Bispecific Nanoblocker for Enhancing Tumor Immunotherapy.

Anti-PD-L1 monoclonal antibody has achieved substantial success in tumor immunotherapy by T-cells activation. However, the excessive accumulation of extracellular matrix components induced by unsatisfactory T-cells infiltration and poor tumor penetration of antibodies make it challenging to realize efficient tumor immunotherapy. Herein, a peptide-based bispecific nanoblocker (BNB) strategy is reported for in situ construction of CXCR4/PD-L1 targeted nanoclusters on the surface of tumor cells that are capable of boosting T-cells infiltration through CXCR4 blockage and enhancing T-cells activation by PD-L1 occupancy, ultimately realizing high-performance tumor immunotherapy. Briefly, the BNB strategy selectively recognizes and bonds CXCR4/PD-L1 with deep tumor penetration, which rapidly self-assembles into nanoclusters on the surface of tumor cells. Compared to the traditional bispecific antibody, BNB exhibits an intriguing metabolic behavior, that is, the elimination half-life (t1/2 ) of BNB in the tumor is 69.3 h which is ≈50 times longer than that in the plasma (1.4 h). The higher tumor accumulation and rapid systemic clearance overcome potential systemic side effects. Moreover, the solid tumor stress generated by excessive extracellular matrix components is substantially reduced to 44%, which promotes T-cells infiltration and activation for immunotherapy efficacy. Finally, these findings substantially strengthen and extend clinical applications of PD-1/PD-L1 immunotherapy.

Programmable Peptides Activated Macropinocytosis for Direct Cytosolic Delivery.

Bioactive macromolecules show great promise for the treatment of various diseases. However, the cytosolic delivery of peptide-based drugs remains a challenging task owing to the existence of multiple intracellular barriers and ineffective endosomal escape. To address these issues, herein, programmable self-assembling peptide vectors are reported to amplify cargo internalization into the cytoplasm through receptor-activated macropinocytosis. Programmable self-assembling peptide vector-active human epidermal growth factor receptor-2 (HER2) signaling induces the receptor-activated macropinocytosis pathway, achieving efficient uptake in tumor cells. Shrinking macropinosomes accelerate the process of assembly dynamics and form nanostructures in the cytoplasm to increase peptide-based cargo accumulation and retention. Inductively coupled plasma mass (ICP-MS) spectrometry quantitative analysis indicates that the Gd delivery efficiency in tumor tissue through the macropinocytosis pathway is improved 2.5-fold compared with that through the use of active targeting molecular delivery. Finally, compared with nanoparticles and active targeting delivery, the delivery of bioactive peptide drugs through the self-assembly of peptide vectors maintains high drug activity (the IC50 decreased twofold) in the cytoplasm and achieves effective inhibition of tumor cell growth. Programmable self-assembling peptide vectors represent a promising platform for the intracellular delivery of diverse bioactive drugs, including molecular drugs, peptides, and biologics.

Nano Proteolysis Targeting Chimeras (PROTACs) with Anti-Hook Effect for Tumor Therapy.

Proteolysis targeting chimera (PROTAC) is an emerging pharmacological modality with innovated post-translational protein degradation capabilities. However, off-target induced unintended tissue effects and intrinsic "hook effect" hinder PROTAC biotechnology to be maturely developed. Herein, an intracellular fabricated nano proteolysis targeting chimeras (Nano-PROTACs) modality with a center-spoke degradation network for achieving efficient dose-dependent protein degradation in tumor is reported. The PROTAC precursors are triggered by higher GSH concentrations inside tumor cells, which subsequently in situ self-assemble into Nano-PROTACs through intermolecular hydrogen bond interactions. The fibrous Nano-PROTACs can form effective polynary complexes and E3 ligases degradation network with multi-binding sites, achieving dose-dependent protein degradation with "anti-hook effect". The generality and efficacy of Nano-PROTACs are validated by degrading variable protein of interest (POI) such as epidermal growth factor receptor (EGFR) and androgen receptor (AR) in a wide-range dose-dependent manner with a 95 % degradation rate and long-lasting potency up to 72 h in vitro. Significantly, Nano-PROTACs achieve in vivo dose-dependent protein degradation up to 79 % and tumor growth inhibition in A549 and LNCap xenograft mice models, respectively. Taking advantages of in situ self-assembly strategy, the Nano-PROTACs provide a generalizable platform to promote precise clinical translational application of PROTAC.

PKM2 allosteric converter: A self-assembly peptide for suppressing renal cell carcinoma and sensitizing chemotherapy.

Stronger intrinsic Warburg effect and resistance to chemotherapy are the responses to high mortality of renal cell carcinoma (RCC). Pyruvate kinase M2 (PKM2) plays an important role in this process. Promoting PKM2 conversion from dimer to tetramer is a critical strategy to inhibit Warburg effect and reverse chemotherapy resistance. Herein, a PKM2 allosteric converter (PAC) is constructed based on the "in vivo self-assembly" strategy, which is able to continuously stimulate PKM2 tetramerization. The PAC contains three motifs, a serine site that is protected by enzyme cleavable ß-N-acetylglucosamine, a self-assembly peptide and a AIE motif. Once PAC nanoparticles reach tumor site via the EPR effect, the protective and hydrophilic ß-N-acetylglucosamine will be removed by over-expressed O-GlcNAcase (OGA), causing self-assembled peptides to transform into nanofibers with large serine (PKM2 tetramer activator) exposure and long-term retention, which promotes PKM2 tetramerization continuously. Our results show that PAC-induced PKM2 tetramerization inhibits aberrant metabolism mediated by Warburg effect in cytoplasm. In this way, tumor proliferation and metastasis behavior could be effectively inhibited. Meanwhile, PAC induced PKM2 tetramerization impedes the nuclear translocation of PKM2 dimer, which restores the sensitivity of cancer cells to first-line anticancer drugs. Collectively, the innovative PAC effectively promotes PKM2 conversion from dimer to tetramer, and it might provide a novel approach for suppressing RCC and enhancing chemotherapy sensitivity.

A bispecific glycopeptide spatiotemporally regulates tumor microenvironment for inhibiting bladder cancer recurrence.

Up to 75% of bladder cancer patients suffer from recurrence due to postoperative tumor implantation. However, clinically used Bacillus Calmette-Guerin (BCG) treatment failed to inhibit the recurrence. Here, we report a bispecific glycopeptide (bsGP) that simultaneously targets CD206 on tumor-associated macrophages (TAMs) and CXCR4 on tumor cells. bsGP repolarizes protumoral M2-like TAMs to antitumor M1-like that mediated cytotoxicity and T cell recruitment. Meanwhile, bsGP is cleaved by the MMP-2 enzyme to form nanostructure for the long-term inhibition of CXCR4 downstream signaling, resulting in reduced tumor metastasis and promoted T cell infiltration. In orthotopic bladder tumor models, bsGP reduced the postoperative recurrence rate to 22%. In parallel, the recurrence rates of 89 and 78% were treated by doxycycline and BCG used in clinic, respectively. Mechanistic studies reveal that bsGP reduces the matrix microenvironment barrier, increasing the spatially redirected CD8+ T cells to tumor cells. We envision that bis-targeting CD206 and CXCR4 may pave the way to inhibit tumor metastasis and recurrence.

Reprogramming Hypoxic Tumor-Associated Macrophages by Nanoglycoclusters for Boosted Cancer Immunotherapy.

The tumor-associated macrophages (TAMs) in intratumoral hypoxic regions are key drivers of immune escape. Reprogramming the hypoxic TAMs to antitumor phenotype holds great therapeutic benefits but remains challenging for current drugs. Here, an in situ activated nanoglycocluster is reported to realize effective tumor penetration and potent repolarization of hypoxic TAMs. Triggered by the hypoxia-upregulated matrix metalloproteinase-2 (MMP-2), the nanoglycocluster is self-assembled from the administered mannose-containing precursor glycopeptides and presents densely-arrayed mannoses to multivalently engage with mannose receptors on M2-like TAMs for efficient phenotype switch. By virtue of the high diffusivity of precursor glycopeptides due to their low molecular mass and weak affinity with TAMs in perivascular regions, the nanoglycoclusters are capable of substantially accumulating in hypoxic areas to strongly interact with local TAMs. This enables the efficient repolarization of overall TAMs with a higher rate than the small-molecule drug R848 and CD40 antibody, and beneficial therapeutic effects in mouse tumor models especially when combining with PD-1 antibody. This on-demand activated immunoagent is endowed with tumor-penetrating properties and inspires the design of diverse intelligent nanomedicines for hypoxia-related cancer immunotherapy.

Localized Instillation Enables In Vivo Screening of Targeting Peptides Using One-Bead One-Compound Technology.

The One-Bead One-Compound (OBOC) library screening is an efficient technique for identifying targeting peptides. However, due to the relatively large bead size, it is challenging for the OBOC method to be applied for in vivo screening. Herein, we report an in vivo Localized Instillation Beads library (LIB) screening method to discover targeting peptides with the OBOC technique. Inspired by localized instillation, we constructed a cavity inside of a transplanted tumor of a mouse. Then, the OBOC heptapeptide library was injected and incubated inside the tumor cavity. After an efficient elution process, the retained beads were gathered, from which three MDA-MB-231 tumor-targeting heptapeptides were discovered. It was verified that the best peptide had 1.9-fold higher tumor accumulation than the commonly used targeting peptide RGD in vivo. Finally, two targeting proteins were discovered as potential targets of our targeting peptide to the MDA-MB-231 tumor. The in vivo LIB screening method expands the scope of OBOC peptide screening applications to discover targeting peptides in vivo feasibly and reliably.

Chaetomadramines A-E, a class of siderophores with potent neuroprotective activity from the fungus Chaetomium madrasense cib-1.

Five hydroxamate siderophores, chaetomadramines A-E (1-5), along with seven known compounds were isolated from the fermented rice culture of the fungus Chaetomium madrasense cib-1. Compounds 1-5 were structurally elucidated on the basis of spectroscopic data, which were a group of unusual hydroxamate siderophores, bearing a long fatty acyl on the α-NH2 of the Nδ-hydroxylated ornithine. Compounds 2-5 were new. The structural elucidation and spectroscopic data of 1 were reported for the first time. Compounds 2-4 significantly improved the survival rates of PC12 cells in the neuroprotective activity assay at the concentration of 40 µM.

Bioinspired Screening of Anti-Adhesion Peptides against Blood Proteins for Intravenous Delivery of Nanomaterials.

Nanomaterials (NMs) inevitably adsorb proteins in blood and form "protein corona" upon intravenous administration as drug carriers, potentially changing the biological properties and intended functions. Inspired by anti-adhesion properties of natural proteins, herein, we employed the one-bead one-compound (OBOC) combinatorial peptide library method to screen anti-adhesion peptides (AAPs) against proteins. The library beads displaying random peptides were screened with three fluorescent-labeled plasma proteins. The nonfluorescence beads, presumed to have anti-adhesion property against the proteins, were isolated for sequence determination. These identified AAPs were coated on gold nanorods (GNRs), enabling significant extension of the blood circulating half-life of these GNRs in mice to 37.8 h, much longer than that (26.6 h) of PEG-coated GNRs. In addition, such AAP coating was found to alter the biodistribution profile of GNRs in mice. The bioinspired screening strategy and resulting peptides show great potential for enhancing the delivery efficiency and targeting ability of NMs.

A novel UBE2A splice site variant causing intellectual disability type Nascimento.

X-linked intellectual disability type Nascimento (XLID) is a rare disease caused by variants in the ubiquitin-conjugating enzyme E2A gene (UBE2A). Patients with XLID have similar phenotypes, including speech impairments, severe intellectual disability, hearing loss, wide facies, synophrys, generalized hirsutism, and urogenital abnormalities. Till date, only two splice-site variants of the UBE2A gene have been observed in patients with X-linked ID type Nascimento. Here, we report the case of a Chinese boy with a syndrome clinically similar to XLID with speech impairment, severe intellectual disability, and moderate hearing loss. However, different characteristics were also present in the patient, including an inability to maintain his head in an upright posture. Both of the patient's palms have a single transverse palmar crease. Subsequent whole-exome sequencing revealed a novel splice site variant in UBE2A (c.241 + 1 G > A). Our study not only expands the variant spectrum and clinical characteristics of UBE2A deficiency syndrome but also provides clinical evidence for genetic diagnoses.