Sustained Secretion of CCL21 via an Implantable Cell Reservoir Hydrogel Enhances the Systemic Antitumor Effect of Radiotherapy.

The combination of radiotherapy (RT) and immunotherapy shows promise in improving the clinical treatment of solid tumors; however, it faces challenges of low response rates and systemic toxicity. Herein, an implantable alginate/collagen hydrogel encapsulating C-C motif ligand 21 (CCL21)-expressing dendritic cells (CCL21-DCs@gel) was developed to potentiate the systemic antitumor effects of RT. The hydrogel functioned as a suitable reservoir for in vivo culture and proliferation of CCL21-DCs, thereby enabling sustained CCL21 release. The local CCL21 gradient induced by CCL21-DCs@gel significantly enhanced the efficacy of RT in suppressing primary tumor growth and inhibiting distant metastasis across several mouse models. Furthermore, the combination of RT with CCL21-DCs@gel provided complete prophylactic protection to mice. Mechanistic investigations revealed that CCL21-DCs@gel potentiated RT by promoting tumor lymphangiogenesis and attracting immune cell infiltration into the tumor. Collectively, these results suggest that CCL21-DCs@gel is a promising adjunct to RT for effectively eradicating tumors and preventing tumor recurrence.

The impact of family socioeconomic status on parental involvement and student engagement during COVID-19 in promoting academic achievement: A longitudinal study in Chinese children.

With a three-wave longitudinal design, the current study examined the impact of family socioeconomic status (SES) on parental involvement and student engagement in promoting children's academic achievement during the coronavirus disease 2019 (COVID-19) pandemic. We recruited data from 246 mother-primary school student dyads, and the mean age of children at Wave 1 was 10.57 ± 0.97 years (range = 9-13 years). The academic achievement of these children was measured both before and after school closures. Family SES, parental involvement, and student engagement were assessed during the school closures. The results indicated that family SES could predict children's later academic achievement after accounting for their prior academic achievement and other demographics (i.e., the significant total effect in the model). Moreover, parental involvement and student engagement played chain-mediating roles in the effect of family SES on children's later academic achievement. Neither parent involvement nor student involvement alone mediated the relationships between family SES and subsequent academic achievement. Suggestions are provided to minimize the negative impact of low family SES on children's academic achievement during pandemics.

Phonological awareness and RAN contribute to Chinese reading and arithmetic for different reasons.

The present study investigated how phonological awareness and rapid automatized naming (hereafter, RAN), simultaneously contributed to Chinese reading and arithmetic fluency. Specifically, we proposed a new hypothesized mechanism that processing speed would mediate the relations of RAN with Chinese reading and arithmetic fluency. One hundred and forty-five Chinese children at the fifth grade were administered with a battery of measures, including three phonological processing measures, character reading, and whole number computation, as well as nonverbal IQ, and vocabulary knowledge. Path analyses revealed that phonological awareness and RAN were uniquely related to character reading and arithmetic fluency, while phonological memory was not significantly correlated to either character reading or arithmetic fluency, after controlling for age, nonverbal IQ, and vocabulary knowledge. Further analysis indicated that processing speed demonstrated a mediating effect on the importance of RAN in character reading, rather than in arithmetic fluency. Results underscore the potential importance of phonological awareness and RAN in character reading and arithmetic fluency, and the mediating role of processing speed in RAN to promote Chinese character reading fluency.

Visual perception and linguistic abilities, not quantitative knowledge, count in geometric knowledge of kindergarten children.

Geometric knowledge is one of the important mathematical skills acquired by children at a young age and is a major area of future mathematical learning; however, there is no direct research on the factors influencing kindergarteners' early geometric knowledge. The pathways model to mathematics was modified to examine the cognitive mechanisms underlying geometric knowledge in Chinese kindergarten children aged 5-7 (n = 99). Quantitative knowledge, visual-spatial processing, and linguistic abilities were stepped into hierarchical multiple regression models. The results revealed that after age, sex, and nonverbal intelligence were statistically controlled, visual perception, phonological awareness, and rapid automatized naming in linguistic abilities significantly predicted the variation in geometric knowledge. For quantitative knowledge, neither dot comparison nor number comparison test could be a significant precursor of geometry skills. The findings indicate that visual perception and linguistic abilities, not quantitative knowledge, account for the geometric knowledge of kindergarten children.

How does working memory matter in young children's arithmetic skills: The mediating role of basic number processing.

The current study investigated whether and how each component of the working memory model was associated with kindergarten children's arithmetic performance. A total of 103 Chinese kindergarten children were administered tests of the visuospatial sketchpad, the phonological loop, the central executive, and basic number processing (i.e., number line estimation, nonverbal numerosity estimation and numerical magnitude comparison). The results showed that among the three working memory components, the central executive accounted for a significant proportion of the variance in young children's arithmetic performance. In terms of basic number processing, number line estimation and numerical magnitude comparison had significant influences on young children's arithmetic performance. Furthermore, numerical magnitude comparison played a mediating role between the visuospatial sketchpad and early arithmetic skills. These findings highlight the importance of working memory and basic number processing in early arithmetic skills and reveal different pathways through which the three working memory components influence young children's arithmetic performance.

Bidirectional relationship between visual perception and mathematics performance in Chinese kindergartners.

In this longitudinal study, 64 kindergartners (mean age at T1 = 4.69 ± 0.33 years; 34 girls) were tested on visual perception skills (T2 and T3) and mathematics performance (T1 to T3) with 6-month intervals between the three testing waves. Cross-lagged path analysis showed a bidirectional relationship between visual perception and mathematics performance from T2 to T3. Specifically, children's visual perception at T2 significantly predicted their mathematics performance at T3 (B = 0.30, SE = 0.14, p = 0.03, ß = 0.19). Children's mathematics performance at T1 accounted for unique variance in visual perception at T2 (B = 0.79, SE = 0.11, p < 0.001, ß = 0.68) and visual perception at T3 (B = 0.27, SE = 0.12, p = 0.02, ß = 0.32). Their mathematics performance at T2 also significantly predicted visual perception at T3 (B = 0.21, SE = 0.10, p = 0.04, ß = 0.28). Totally, they explained 61% of the variance in mathematics performance and 39% of the variance in visual perception at T3. The results highlight the developmental courses as well as the reciprocal facilitations between visual perception and mathematics performance in the kindergarten period.

Failure of resting-state frontal-occipital connectivity in linking visual perception with reading fluency in Chinese children with developmental dyslexia.

It is widely accepted that impairment in visual perception impedes children's reading development, and further studies have demonstrated significant enhancement in reading fluency after visual perceptual training. However, the mechanism of the neural linkage between visual perception and reading is unclear. The purpose of this study was to examine the intrinsic functional relationship between visual perception (indexed by the texture discrimination task,TDT) and reading ability (character reading and reading fluency) in Chinese children with developmental dyslexia (DD) and those with typical development (TD). The resting-state functional connectivity (RSFC) between the primary visual cortex (V1, BA17) and the entire brain was analyzed. In addition, how RSFC maps are associated with TDT performance and reading ability in the DD and TD groups was examined. The results demonstrated that the strength of the RSFC between V1 and the left middle frontal gyrus (LMFG, BA9/BA46) was significantly correlated with both the threshold (SOA) of the TDT and reading fluency in TD children but not in DD children. Moreover, LMFG-V1 resting-state connectivity played a mediating role in the association of visual texture discrimination and reading fluency, but not in character reading, in TD children. In contrast, this mediation was absent in DD children, albeit their strengths of RSFC between V1 and the left middle frontal gyrus (LMFG) were comparable to those for the TD group. These findings indicate that typically developing children use the linkage of the RSFC between the V1 and LMFG for visual perception skills, which in turn promote fluent reading; in contrast, children with dyslexia, who had higher TDT thresholds than TD children, could not take advantage of their frontal-occipital connectivity to improve reading fluency abilities. These findings suggest that visual perception plays an important role in reading skills and that children with developmental dyslexia lack the ability to use their frontal-occipital connectivity to link visual perception with reading fluency.

Visual-spatial skills contribute to Chinese reading and arithmetic for different reasons: A three-wave longitudinal study.

Previous literature has revealed that visual-spatial processing is associated with both reading and arithmetic. Yet the strength of their relations and the reasons why visual-spatial processing contributes to reading and arithmetic remain ambiguous. The current study focused on two types of visual-spatial skills that recent evidence has suggested are crucial in children's early reading and arithmetic development: visual-perceptual and spatial visualization skills. With an interval of 6 months, we assessed 104 Hong Kong kindergarten children's visual-spatial skills, word reading, arithmetic performance, and vocabulary knowledge at Wave 1; orthographic awareness, basic number knowledge, and number line estimation at Wave 2; and Chinese word reading and arithmetic performance at Wave 3. Correlational analysis showed that both visual-perceptual and spatial visualization skills were associated with later Chinese word reading and arithmetic performance. Further mediation analyses revealed that spatial visualization skills, rather than visual-perceptual skills, contributed to Chinese word reading via orthographic awareness and also predicted arithmetic performance through basic number knowledge. However, number line estimation failed to mediate any relations of visual-spatial skills with children's arithmetic abilities. The results suggest the importance of visual-spatial processing in Chinese word reading and mathematics, with spatial visualization contributing to reading and mathematics for different reasons.

How do phonological awareness, rapid automatized naming, and vocabulary contribute to early numeracy and print knowledge of Filipino children?

The current study investigated the contributions of phonological awareness, rapid automatized naming (RAN), and vocabulary to early numeracy and print knowledge developmental trajectories. A total of 128 young Filipino children were tracked three times at mean ages of 4.5, 5.0, and 5.5 years. The initial level (the intercept) and the growth rate (the slope) of early numeracy and print knowledge were estimated. Results showed that phonological awareness, vocabulary, and age significantly predicted the initial level of early numeracy. RAN and vocabulary explained significant variance in the growth rate of early numeracy. Phonological awareness, RAN, and vocabulary accounted for unique variance in the initial level of print knowledge. Results highlight the differential roles of phonological awareness, RAN, and vocabulary knowledge in the development of early numeracy and print knowledge among Filipino children.

Fabrication of novel MXene (Ti3C2)/polyacrylamide nanocomposite hydrogels with enhanced mechanical and drug release properties.

A highly stretchable nanocomposite (NC) hydrogel was fabricated via in situ free radical polymerization of acrylamide. In particular, an exfoliated two-dimensional MXene (Ti3C2) nanosheet was utilized as a crosslinker instead of traditional organic crosslinkers. The exfoliated Ti3C2 nanosheets were confirmed by atomic force microscopy (AFM) and dynamic light scattering (DLS) measurements. Compared with traditional organic crosslinked N,N-methylene bisacrylamide (BIS)/polyacrylamide (PAM) hydrogels (fracture strength of 32.0 kPa and elongation of 109.6%), the synthesized Ti3C2/PAM NC hydrogels exhibited greatly improved mechanical properties with fracture strengths of 66.5 to 102.7 kPa, compressive strengths of 400.6 to 819.4 kPa and elongations at break of 2158.6% to 3047.5% as the Ti3C2 content increases from 0.0145% to 0.0436%. The enhanced mechanical performances can be attributed to the honeycomb-like fine structure with uniform pores as well as more flexible polymer chains in NC hydrogel networks. When loaded with drugs, Ti3C2/PAM NC hydrogels exhibited good sustained-release performance, higher drug loading amounts (97.5-127.7 mg g-1) and higher percentage releases (62.1-81.4%), greatly superior to those of the BIS/PAM hydrogel (46.4 mg g-1, 45.0%). Our work reveals the application of MXene materials in the fabrication of NC hydrogels with enhanced mechanical and drug release behaviors.

Effect of Twinning on Chinese and English Vocabulary Knowledge.

Vocabulary knowledge was tested in a native (Cantonese-Chinese) and foreign (English) language in 150 twins and 150 singletons aged 6-11 years, matched on age, gender, grade level, nonverbal intelligence, parents' education, family income, and number of siblings and household members. The singletons clearly outperformed the twins on the native vocabulary, but this "twinning effect" was much less noticeable for the foreign vocabulary. The effect on English vocabulary was further reduced after exposure to English at home was controlled. Given that these participants learned most of their English in school rather than home, the present findings support the notion that the twinning effect is associated with increased competition for family interaction in twins compared with singletons.

Structural correlates of literacy difficulties in the second language: Evidence from Mandarin-speaking children learning English.

Several neuroimaging studies have explored the neural basis of literacy difficulties in the second language (L2). However, it remains unclear whether the associated neural alterations are related to literacy abilities in the first language (L1). Using magnetic resonance imaging, we explore this issue with two experiments in Mandarin-speaking children learning English as second language. In the first experiment, we investigated children with literacy difficulties in L2 and L1 (poor in both, PB) and children with literacy difficulties only in L2 (poor in English, PE). We compared the brain structure in these two groups to a control literacy (CL) group. The results showed that the CL group had significantly less gray matter volume in the left supramarginal gyrus compared to the PB group and moderately less gray matter volume compared to the PE group. In addition, the PB group had significant greater gray matter volume in the left medial fusiform gyrus compared to the PE group and had marginally greater gray matter volume compared to the CL group. In the second experiment, we explored the relationship between the two atypical regions and literacy abilities in the two languages in an independent sample consisting of children with typical literacy. Correlation analyses revealed that the left supramarginal gyrus was significantly associated with literacy performance only in the second language, English, whereas the left medial fusiform gyrus did not correlate with the performances in either L1 or L2. Taken together, these findings suggest that literacy difficulties in an alphabetic L2 are associated with a structural abnormality in the left supramarginal gyrus, a region implicated in phonological processing, which is independent of literacy abilities in the native language.

Dyslexic Children Show Atypical Cerebellar Activation and Cerebro-Cerebellar Functional Connectivity in Orthographic and Phonological Processing.

Previous neuroimaging studies have found atypical cerebellar activation in individuals with dyslexia in either motor-related tasks or language tasks. However, studies investigating atypical cerebellar activation in individuals with dyslexia have mostly used tasks tapping phonological processing. A question that is yet unanswered is whether the cerebellum in individuals with dyslexia functions properly during orthographic processing of words, as growing evidence shows that the cerebellum is also involved in visual and spatial processing. Here, we investigated cerebellar activation and cerebro-cerebellar functional connectivity during word processing in dyslexic readers and typically developing readers using tasks that tap orthographic and phonological codes. In children with dyslexia, we observed an abnormally higher engagement of the bilateral cerebellum for the orthographic task, which was negatively correlated with literacy measures. The greater the reading impairment was for young dyslexic readers, the stronger the cerebellar activation was. This suggests a compensatory role of the cerebellum in reading for children with dyslexia. In addition, a tendency for higher cerebellar activation in dyslexic readers was found in the phonological task. Moreover, the functional connectivity was stronger for dyslexic readers relative to typically developing readers between the lobule VI of the right cerebellum and the left fusiform gyrus during the orthographic task and between the lobule VI of the left cerebellum and the left supramarginal gyrus during the phonological task. This pattern of results suggests that the cerebellum compensates for reading impairment through the connections with specific brain regions responsible for the ongoing reading task. These findings enhance our understanding of the cerebellum's involvement in reading and reading impairment.

The relation between approximate number system and early arithmetic: The mediation role of numerical knowledge.

We investigated whether the approximate number system (ANS) was related to arithmetic among kindergartners and the mechanism underlying this possible relation. Specifically, we examined whether numerical knowledge mediated the possible relation between the ANS and arithmetic after controlling for potential confounding cognitive variables. Results showed that the ANS was moderately related with early arithmetic (r=.36-.37). After controlling for age, IQ, visual attention, working memory, visuospatial processing, and inhibition, numerical knowledge demonstrated a medium mediation effect (k2=.09) on the relation between the ANS and arithmetic. Our findings suggest the importance of the ANS in early arithmetic and support the numerical knowledge mediation hypothesis. That is, numerical knowledge plays a more important role than visuospatial processing and inhibition in explaining the relation between the ANS and early arithmetic. Implications of these findings for early arithmetic instructions are discussed.

Synthesis of diastereometrically pure cubane-like photodimers from 2,4-pentanediyl-bis-2-naphthoates.

Irradiation of (2R,4R)-(-)- and (2S,4S)-(+)-2,4-pentanediyl-bis-2-naphthoates (1R and 1S, respectively) in organic solutions exclusively results in cubane-like anti(HH) photodimers in 100% yield. Asymmetric induction with 100% diastereometric excess (de) has been achieved and the absolute configuration of the yielded diastereomers has been established. Moreover, irradiation of (2R,4S)-2,4-pentanediyl-bis-2-naphthoate (1M) gives cubane-like syn(HH) photodimers in 100% yield.

The longitudinal contribution of mapping to arithmetic: Do numeral knowledge, inhibition or analogical reasoning matter?

BACKGROUND: Recent studies have revealed the association between mapping and arithmetic (Ferres-Forga et al., J. Numer. Cogn., 8, 2022, 123; LeFevre et al., J. Numer. Cogn., 8, 2022, 1). AIM: The underlying mechanism remains unclear. MATERIALS & METHODS: The current study recruited 118 kindergarten children and followed up on them three times at 6-month intervals. They completed measures to assess mapping skills (T1), non-verbal IQ (T1), numeral knowledge (T2), inhibitory control (T2), analogical reasoning (T2) and arithmetic (T3). RESULTS: The results showed that mapping accounted for significant variance in arithmetic ability over and above age, gender and non-verbal IQ. Furthermore, analogical reasoning played an important role in the relationship between mapping and mathematics ability. DISCUSSION: The findings suggest the association between mapping and mathematics ability prior to formal schooling. CONCLUSION: Analogical reasoning, rather than numeral knowledge or inhibitory control, may drive that association in young children.

Brain development of a school-aged boy with autism spectrum condition talented in arithmetic: a case report.

Whereas autism spectrum condition is known for its social and communicative challenges, some autistic children demonstrate unusual islets of abilities including those related to mathematics, the neurobiological underpinnings of which are increasingly becoming the focus of research. Here we describe an 8-year-old autistic boy with intellectual and language challenges, yet exceptional arithmetic ability. He can perform verbal-based multiplication of three- and even four-digit numbers within 20 seconds. To gain insights into the neural basis of his talent, we investigated the gray matter in the child's brain in comparison to typical development, applying voxel-based morphometry to magnetic resonance imaging data. The case exhibited reduced gray matter volume in regions associated with arithmetic, which may suggest an accelerated development of brain regions with arithmetic compared to typically developing individuals: potentially a key factor contributing to his exceptional talent. Taken together, this case report describes an example of the neurodiversity of autism. Our research provides valuable insights into the potential neural basis of exceptional arithmetic abilities in individuals with the autism spectrum and its potential contribution to depicting the diversity and complexity of autism.

Noninvasively Deciphering the Immunosuppressive Tumor Microenvironment Using Galectin-1 PET to Inform Immunotherapy Responses.

Immune checkpoint blockade (ICB) has achieved groundbreaking results in clinical cancer therapy; however, only a subset of patients experience durable benefits. The aim of this study was to explore strategies for predicting tumor responses to optimize the intervention approach using ICB therapy. Methods: We used a bilateral mouse model for proteomics analysis to identify new imaging biomarkers for tumor responses to ICB therapy. A PET radiotracer was synthesized by radiolabeling the identified biomarker-targeting antibody with 124I. The radiotracer was then tested for PET prediction of tumor responses to ICB therapy. Results: We identified galectin-1 (Gal-1), a member of the carbohydrate-binding lectin family, as a potential negative biomarker for ICB efficacy. We established that Gal-1 inhibition promotes a sensitive immune phenotype within the tumor microenvironment (TME) for ICB therapy. To assess the pre-ICB treatment status of the TME, a Gal-1-targeted PET radiotracer, 124I-αGal-1, was developed. PET imaging with 124I-αGal-1 showed the pretreatment immunosuppressive status of the TME before the initiation of therapy, thus enabling the prediction of ICB resistance in advance. Moreover, the use of hydrogel scaffolds loaded with a Gal-1 inhibitor, thiodigalactoside, demonstrated that a single dose of thiodigalactoside-hydrogel significantly potentiated ICB and adoptive cell transfer immunotherapies by remodeling the immunosuppressive TME. Conclusion: Our study underscores the potential of Gal-1-targeted PET imaging as a valuable strategy for early-stage monitoring of tumor responses to ICB therapy. Additionally, Gal-1 inhibition effectively counteracts the immunosuppressive TME, resulting in enhanced immunotherapy efficacy.

[Treatment of upper respiratory infection by fangfeng tongsheng granule: a randomized controlled study].

OBJECTIVE: To evaluate the clinical effectiveness and safety of Fangfeng Tongsheng Granule (FTG) in the treatment of upper respiratory infection (superficial cold and interior heat syndrome, exterior and interior excess syndrome). METHODS: A randomized, double-blinded, multi-centered, placebo-parallel-controlled clinical trial was adopted. Totally 324 patients were enrolled and assigned to two groups, 216 patients in the treatment group and 108 patients in the control group. Those in the treatment group took FTG at the daily dose of 3 g, twice per day, the therapeutic course being 3 days. Those with axillary temperature more than 37 degrees C took one more time before medication. Those in the control group took simulated agent granules the same dose and dosage as the treatment group. The effect of Chinese medical syndrome (ECMS), the rate of temperature-dropping-to-normal (RT), the time of temperature-dropping-to-normal (TT), the curative effect of single symptom (CESS) and adverse reactions were observed. RESULTS: Totally 203 completed the trial in the treatment group and 101 in the control group. In the treatment group, the cured-effective rate was 55.67% (113/ 101), the total effective rate was 93.10% (189/101), the ECMS score decreased by 9.24 +/- 4.46, while they were 5.94% (6/101), 36.63% (37/101), and 3.27 +/- 3.29, respectively in the control group (P < 0.01). The RT was 87.50% (98/112) in the treatment group and 58.49% (31/53) in the control group (P < 0.01). The TT in the treatment group was superior to that of the control group (P < 0.01). As for CESS, all of the three primary symptoms and nine secondary symptoms were improved more obviously in the treatment group than in the control group. The integral decreased obviously, showing statistical difference (P < 0.01). The decrease was more obvious in the treatment group than in the control group (P < 0.01). There was no adverse event related to FTG. CONCLUSION: FTG was effective and safe in treating upper respiratory infection (superficial cold and interior heat syndrome, exterior and interior excess syndrome).

COVID-19 and Eating Problems in Daily Life: The Mediating Roles of Stress, Negative Affect and Posttraumatic Stress Symptoms.

Background The COVID-19 pandemic poses a challenge to individuals' mental health. People worldwide are experiencing increased stress, negative affect, and posttraumatic stress symptoms, which may lead to eating problems. The purpose of this study was to explore the impact of the perceived severity of COVID-19 on eating problems and the mediating effects of stress/negative affect/posttraumatic stress symptoms both at the personal level and interpersonal level. Methods: During the COVID-19 outbreak, a total of 108 college students were recruited to report their perceived severity of COVID-19, stress, negative affect, posttraumatic stress symptoms, and eating problems three times a day for seven consecutive days using Ecological Momentary Assessment. Results: State perceived severity of COVID-19 predicted fewer subsequent eating problems in daily life at the personal level. Both state negative affect and posttraumatic stress symptoms were positively associated with eating problems in daily life. At the interpersonal level, trait-like perceived severity of COVID-19, stress, negative affect, and posttraumatic stress symptoms were positively associated with overall eating problems. There were no mediating effects of stress/negative affect/posttraumatic stress symptoms on the relations between perceived severity of COVID-19 and eating problems at the personal/interpersonal level. Conclusions: The perceived severity of COVID-19, stress, negative affect, and posttraumatic stress symptoms might increase the risk of eating problems.